nct_id
stringlengths 11
11
| brief_title
stringlengths 7
300
| brief_summary
stringlengths 0
4.99k
| detailed_descriptions
stringlengths 0
31.8k
| official_title
stringlengths 16
598
⌀ | conditions
stringlengths 0
11k
| interventions
stringlengths 0
3.18k
| eligibility_criteria
stringlengths 0
19.6k
⌀ | minimum_age
stringclasses 304
values | maximum_age
stringclasses 448
values | gender
stringclasses 4
values | healthy_volunteers
stringclasses 3
values | design_details
stringlengths 0
1.17k
| primary_outcome_measures
stringlengths 75
136k
| secondary_outcome_measures
stringlengths 0
185k
| keywords
stringlengths 0
18.8k
| mesh_terms
stringlengths 0
8.39k
| arms_and_interventions
stringlengths 0
109k
| structured_text
stringlengths 539
193k
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
NCT02565875
|
Standardizing Language in Laparoscopic Surgery
|
Obstetrics and Gynecology residents, fellows and attending physicians will be randomized to view one of two educational presentations of equal duration. The intervention presentation will demonstrate the use of a standardized language for effective communication of laparoscopy commands. Both groups will be asked to perform a simulated laparoscopic task. Participants will be timed and use of the standardized language will be tracked and tabulated. The primary outcome of interest is whether the use of standard commands during a simulated laparoscopic task is associated with sooner completion of the task. This may translate into improved efficiency in the operating room.
|
Background~Continuous communication between the primary surgeon and assistant(s) during laparoscopic surgery is essential. The primary surgeon is rarely in direct control of the laparoscope and visual field. The use of a standard vernacular during surgery to provide clear instructions across all surgical centers is currently not employed. As the theoretical benefits of this are clear, a national survey produced a lexicon of commands1. Despite making intuitive sense, there is presently no evidence to demonstrate a benefit from using this standardized language during laparoscopic surgery. We aim to show that in doing so, there will be a significant improvement in speed and efficiency when performing a complex laparoscopic task.~Objective~To explore whether standardization of communication between the primary surgeon and the assistant in a simulated laparoscopic environment decreases the time needed to perform a complex task.~Materials and Methods~All subjects will provide demographic data, which will be collected through a brief questionnaire. This questionnaire will collect information regarding level of training or years of practice, as well as handedness. Personal identifying information (PII) will not be collected.~Subjects will be block randomized into control and intervention groups by random number generation. Block randomization will preserve equivalent distribution of level of training or years in practice into each group. Secondarily, handedness will be evenly distributed among groups, but not superseding level of training or years in practice.~The intervention group will receive a presentation on the standardized laparoscopic lexicon (SLL) (Mehdizadeh et al). The presentation will focus on sections 1-3 (surgical roles, camera commands and instrument commands).~The control group will receive no pre-task presentation.~Members within each group will be assigned a laparoscopic trainer by random allocation (blinded selection of card denoting station assignment). Through this, each trainer will have 2 subjects of the same group randomly assigned to it. These subjects will be referred to as the primary surgeon and assistant. Assignment of initial roles will be done randomly. A member in each pair will be assigned the role denoted on a card he/she chooses blindly.~Pairs will be provided the task of placing a ball into a bag and closing the opening through tensioning the drawstring. This task must be performed using only laparoscopic graspers and will be timed by invigilators.~The ball will be approximately the same diameter as the bag opening and large enough to require camera adjustments. This task is not a commonly practiced laparoscopic skill such as suturing or knot tying (therefore should be less influenced by level of training) and should require communication between primary surgeon and assistant to accomplish in a timely fashion. The task is complex and should require sufficient time to detect a difference between groups.~Data collection within each group will include each pair's time to completion of the task and level of training/years in practice of primary surgeon and assistant. Invigilators will track the usage of SLL during the task in both groups.~After a break, the roles will be reversed and the task repeated. The same data will be collected.
|
Does Standardizing Language in Laparoscopic Surgery Improve Efficiency? A Randomized Controlled Trial
|
Procedure Time, Communication
|
* Behavioral: SLL Presentation
* Behavioral: Control Presentation
* Other: Simulated laparoscopic task
|
Inclusion Criteria:~Obstetrics and Gynecology Residents OR fellows OR attending physicians~Exclusion Criteria:~Physical disability preventing the candidate from performing laparoscopic surgery
|
19 Years
|
70 Years
|
All
|
Accepts Healthy Volunteers
|
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure Time | The simulated laparoscopic task will be timed from initiation to completion | Recorded once per simulated laparoscopic task upon completion (one visit) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Communication | Tabulated instances of the use of SLL during simulated laparoscopic task from initiation to completion | Recorded during per simulated laparoscopic task (one visit) |
|
Efficiency, Organizational, Simulation, Communication, Laparoscopy, Medical Education
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SLL Presentation<br>Intervention: Standardized Language of Laparoscopy (SLL) Presentation and simulated laparoscopic task performed on a low-fidelity pelvis simulator~Will witness a presentation on the use of a SLL for communication between the primary and assistant surgeons during laparoscopy as previously determined by a national survey of Canadian experts and a modified delphi technique. | Behavioral: SLL Presentation<br>* Educational presentation on the use of a standardized lexicon for communication between surgeon and assistant during laparoscopy<br>Other: Simulated laparoscopic task<br>* Using a low-fidelity pelvis simulator and laparoscopic instruments, pairs of each arm will be asked to perform a laparoscopic task (maneuver a ball into a nylon surgical bag). Use of SLL will be tabulated and task will be timed.<br>|
| Placebo Comparator: Control Presentation<br>Intervention: Surgical Anatomy (SA) Presentation and simulated laparoscopic task performed on a low-fidelity pelvis simulator~Will witness a presentation of similar duration as the intervention group on laparoscopy but not related to communication (laparoscopic anatomy). The simulated laparoscopic task will be identical to the SLL group. | Behavioral: Control Presentation<br>* Educational presentation on relevant anatomy related to laparoscopy performed by a gynecologic surgeon.<br>Other: Simulated laparoscopic task<br>* Using a low-fidelity pelvis simulator and laparoscopic instruments, pairs of each arm will be asked to perform a laparoscopic task (maneuver a ball into a nylon surgical bag). Use of SLL will be tabulated and task will be timed.<br>|
|
Standardizing Language in Laparoscopic Surgery
Study Overview
=================
Brief Summary
-----------------
Obstetrics and Gynecology residents, fellows and attending physicians will be randomized to view one of two educational presentations of equal duration. The intervention presentation will demonstrate the use of a standardized language for effective communication of laparoscopy commands. Both groups will be asked to perform a simulated laparoscopic task. Participants will be timed and use of the standardized language will be tracked and tabulated. The primary outcome of interest is whether the use of standard commands during a simulated laparoscopic task is associated with sooner completion of the task. This may translate into improved efficiency in the operating room.
Detailed Description
-----------------
Background Continuous communication between the primary surgeon and assistant(s) during laparoscopic surgery is essential. The primary surgeon is rarely in direct control of the laparoscope and visual field. The use of a standard vernacular during surgery to provide clear instructions across all surgical centers is currently not employed. As the theoretical benefits of this are clear, a national survey produced a lexicon of commands1. Despite making intuitive sense, there is presently no evidence to demonstrate a benefit from using this standardized language during laparoscopic surgery. We aim to show that in doing so, there will be a significant improvement in speed and efficiency when performing a complex laparoscopic task. Objective To explore whether standardization of communication between the primary surgeon and the assistant in a simulated laparoscopic environment decreases the time needed to perform a complex task. Materials and Methods All subjects will provide demographic data, which will be collected through a brief questionnaire. This questionnaire will collect information regarding level of training or years of practice, as well as handedness. Personal identifying information (PII) will not be collected. Subjects will be block randomized into control and intervention groups by random number generation. Block randomization will preserve equivalent distribution of level of training or years in practice into each group. Secondarily, handedness will be evenly distributed among groups, but not superseding level of training or years in practice. The intervention group will receive a presentation on the standardized laparoscopic lexicon (SLL) (Mehdizadeh et al). The presentation will focus on sections 1-3 (surgical roles, camera commands and instrument commands). The control group will receive no pre-task presentation. Members within each group will be assigned a laparoscopic trainer by random allocation (blinded selection of card denoting station assignment). Through this, each trainer will have 2 subjects of the same group randomly assigned to it. These subjects will be referred to as the primary surgeon and assistant. Assignment of initial roles will be done randomly. A member in each pair will be assigned the role denoted on a card he/she chooses blindly. Pairs will be provided the task of placing a ball into a bag and closing the opening through tensioning the drawstring. This task must be performed using only laparoscopic graspers and will be timed by invigilators. The ball will be approximately the same diameter as the bag opening and large enough to require camera adjustments. This task is not a commonly practiced laparoscopic skill such as suturing or knot tying (therefore should be less influenced by level of training) and should require communication between primary surgeon and assistant to accomplish in a timely fashion. The task is complex and should require sufficient time to detect a difference between groups. Data collection within each group will include each pair's time to completion of the task and level of training/years in practice of primary surgeon and assistant. Invigilators will track the usage of SLL during the task in both groups. After a break, the roles will be reversed and the task repeated. The same data will be collected.
Official Title
-----------------
Does Standardizing Language in Laparoscopic Surgery Improve Efficiency? A Randomized Controlled Trial
Conditions
-----------------
Procedure Time, Communication
Intervention / Treatment
-----------------
* Behavioral: SLL Presentation
* Behavioral: Control Presentation
* Other: Simulated laparoscopic task
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obstetrics and Gynecology Residents OR fellows OR attending physicians Exclusion Criteria: Physical disability preventing the candidate from performing laparoscopic surgery
Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SLL Presentation<br>Intervention: Standardized Language of Laparoscopy (SLL) Presentation and simulated laparoscopic task performed on a low-fidelity pelvis simulator Will witness a presentation on the use of a SLL for communication between the primary and assistant surgeons during laparoscopy as previously determined by a national survey of Canadian experts and a modified delphi technique. | Behavioral: SLL Presentation<br>* Educational presentation on the use of a standardized lexicon for communication between surgeon and assistant during laparoscopy<br>Other: Simulated laparoscopic task<br>* Using a low-fidelity pelvis simulator and laparoscopic instruments, pairs of each arm will be asked to perform a laparoscopic task (maneuver a ball into a nylon surgical bag). Use of SLL will be tabulated and task will be timed.<br>|
| Placebo Comparator: Control Presentation<br>Intervention: Surgical Anatomy (SA) Presentation and simulated laparoscopic task performed on a low-fidelity pelvis simulator Will witness a presentation of similar duration as the intervention group on laparoscopy but not related to communication (laparoscopic anatomy). The simulated laparoscopic task will be identical to the SLL group. | Behavioral: Control Presentation<br>* Educational presentation on relevant anatomy related to laparoscopy performed by a gynecologic surgeon.<br>Other: Simulated laparoscopic task<br>* Using a low-fidelity pelvis simulator and laparoscopic instruments, pairs of each arm will be asked to perform a laparoscopic task (maneuver a ball into a nylon surgical bag). Use of SLL will be tabulated and task will be timed.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure Time | The simulated laparoscopic task will be timed from initiation to completion | Recorded once per simulated laparoscopic task upon completion (one visit) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Communication | Tabulated instances of the use of SLL during simulated laparoscopic task from initiation to completion | Recorded during per simulated laparoscopic task (one visit) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Efficiency, Organizational, Simulation, Communication, Laparoscopy, Medical Education
|
|
NCT02484105
|
Comforting Conversation During Colonoscopy: A Trial on Patient Satisfaction
|
Does comforting conversation during colonoscopy improve on patient satisfaction, compliance and pain management.
|
Does comforting conversation during colonoscopy improve on patient satisfaction, compliance and pain management. A randomized controlled trial on comforting conversation or standard communication during colonoscopy. Using a mixed methods model, a qualitative study will be conducted to clarify what patients deem as important or effective conversation during colonoscopy. A randomized controlled trial will hereafter be conducted, where the results from the initial study will be utilized in the conversation during colonoscopy.
|
Comforting Conversation During Colonoscopy: A Randomised Controlled Trial on Patient Satisfaction
|
Colonoscopy
|
* Behavioral: Comforting Conversation
* Behavioral: Standard Communication
|
Inclusion Criteria:~Age 18-85~Colonoscopy~Written informed content~Exclusion Criteria:~ASA Class 4 or higher~BMI 40 or higher~Analgesics taken prior to procedure~Pregnancy or breast feeding~Allergy to Fentanyl/Midazolam~Daily consumption of opioids~Unable to complete questionnaire
|
18 Years
|
85 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Satisfaction | Questionnaire with 5 point Likert like scale | on average 20 minutes after completed colonoscopy. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per-procedural Pain management | Pain/discomfort prior to-, every 5. minutes and post-procedure with patients using the Visual Analogue Scale | From inclusion to completed procedure. On average 45 minutes from first to last measurement. |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Comforting Conversation<br>Conversation according to the initital qualitative study. | Behavioral: Comforting Conversation<br>* Pain management, distraction, diversion, empathy. Dependent on qualitative study results.<br>Behavioral: Standard Communication<br>* Information on procedure type, duration, findings, key landmarks, possibility of analgesic treatment, pause in procedure.<br>|
| Active Comparator: Standard Communication<br>Standard information prior to and during endoscopy. | Behavioral: Standard Communication<br>* Information on procedure type, duration, findings, key landmarks, possibility of analgesic treatment, pause in procedure.<br>|
|
Comforting Conversation During Colonoscopy: A Trial on Patient Satisfaction
Study Overview
=================
Brief Summary
-----------------
Does comforting conversation during colonoscopy improve on patient satisfaction, compliance and pain management.
Detailed Description
-----------------
Does comforting conversation during colonoscopy improve on patient satisfaction, compliance and pain management. A randomized controlled trial on comforting conversation or standard communication during colonoscopy. Using a mixed methods model, a qualitative study will be conducted to clarify what patients deem as important or effective conversation during colonoscopy. A randomized controlled trial will hereafter be conducted, where the results from the initial study will be utilized in the conversation during colonoscopy.
Official Title
-----------------
Comforting Conversation During Colonoscopy: A Randomised Controlled Trial on Patient Satisfaction
Conditions
-----------------
Colonoscopy
Intervention / Treatment
-----------------
* Behavioral: Comforting Conversation
* Behavioral: Standard Communication
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-85 Colonoscopy Written informed content Exclusion Criteria: ASA Class 4 or higher BMI 40 or higher Analgesics taken prior to procedure Pregnancy or breast feeding Allergy to Fentanyl/Midazolam Daily consumption of opioids Unable to complete questionnaire
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Comforting Conversation<br>Conversation according to the initital qualitative study. | Behavioral: Comforting Conversation<br>* Pain management, distraction, diversion, empathy. Dependent on qualitative study results.<br>Behavioral: Standard Communication<br>* Information on procedure type, duration, findings, key landmarks, possibility of analgesic treatment, pause in procedure.<br>|
| Active Comparator: Standard Communication<br>Standard information prior to and during endoscopy. | Behavioral: Standard Communication<br>* Information on procedure type, duration, findings, key landmarks, possibility of analgesic treatment, pause in procedure.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Satisfaction | Questionnaire with 5 point Likert like scale | on average 20 minutes after completed colonoscopy. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per-procedural Pain management | Pain/discomfort prior to-, every 5. minutes and post-procedure with patients using the Visual Analogue Scale | From inclusion to completed procedure. On average 45 minutes from first to last measurement. |
|
||
NCT03233854
|
CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells With or Without NKTR-255 in Adults With Recurrent or Refractory B Cell Malignancies
|
This phase I trial studies the side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy and NKTR-255, and to see how well they work in treating patients with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on diffuse large B-cell lymphoma and B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. NKTR-255 is an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer. Giving CD19/CD22-CAR T cells and chemotherapy in combination with NKTR-255 may work better in treating patients with diffuse large B-cell lymphoma or B acute lymphoblastic leukemia.
|
PRIMARY OBJECTIVES:~I. Determine the feasibility of producing CD19/CD22 CAR T cells meeting the established release criteria.~II. Assess the safety of administering escalating doses of autologous CD19/CD22 CAR T cells that meet established release specifications in adults with B cell hematologic malignancies following a cyclophosphamide/fludarabine conditioning regimen.~III. Assess the safety and feasibility of administering repeated doses of NKTR-255 intravenously after CD19/CD22-CAR T cell infusions in adults with ALL using a dose escalation design.~IV. Determine the recommended phase 2 dose (RP2D) of NKTR-255 when administered following CD19/CD22-CAR T cell infusion in adults with ALL~SECONDARY OBJECTIVES:~I. Evaluate the ability of CD19/CD22 CAR T cells to mediate clinical activity in adults with DLBCL and adults with ALL.~II. Characterize the pharmacokinetics (PK) of NKTR-255 when administered post CD19/CD22 CAR T cell infusion.~III. Explore the rate of relapse, progression free survival (PFS) and overall survival (OS) in subjects receiving CD19/CD22 CAR T cells, followed by up to 6 cycles of NKTR-255
|
Phase 1 Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells With or Without NKTR-255 in Adults With Recurrent or Refractory B Cell Malignancies
|
B Acute Lymphoblastic Leukemia, CD19 Positive, Minimal Residual Disease, Philadelphia Chromosome Positive
|
* Biological: Chimeric Antigen Receptor T-Cell Therapy
* Drug: Cyclophosphamide
* Drug: Fludarabine Phosphate
* Other: Laboratory Biomarker Analysis
* Other: Questionnaire Administration
* Drug: NKTR-255
|
For B acute lymphoblastic leukemia (ALL)~Confirmed diagnosis of relapsed or refractory B-cell ALL of one of the following types:~Chemotherapy refractory disease in subjects with B-ALL, defined as progression or stable disease after one line of therapy.~Recurrence of disease after achieving CR.~Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, FISH, or next generation sequencing) require verification of MRD positivity on two occasions at least 4 weeks apart.~Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed after receiving a tyrosine kinase inhibitor (TKI).~Subjects with recurrence of isolated CNS relapse after achieving complete remission (CR); if relapsed with MRD, will require verification of MRD positivity on two occasions at least 4 weeks apart.~CD19 positive expression- CD19 expression is required at any time since diagnosis. If patient has received anti-CD19 targeted therapy (i.e. Blinatumomab or CD19-CAR T cells), then CD19 expression must be subsequently demonstrated. CD19 expression may be detected by immunohistochemistry or by flow cytometry. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each subject. In general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples.~Subjects who have undergone autologous SCT with disease progression or relapse following SCT are eligible. Subjects who have undergone allogeneic SCT will be eligible if, in addition to meeting other eligibility criteria, they have elelino evidence of GVHD and have been without immunosuppressive agents for at least 30 days.~Subjects who have undergone prior anti-CD19 or anti-CD22 CAR therapy must be at least 30 days post CAR infusion and may not have eficence of persistnce of CAR T cells in blood smples (circulating levels of genetically modified cels of >/= 5% by flow cytometry.~Must have evaluable or measurable disease. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.~At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives.~Exceptions:~There is no time restriction with regard to prior intrathecal chemotherapy (incl. steroids) provided there is complete recovery from any acute toxic effects;~Subjects who are on standard ALL maintenance type chemotherapy (vincristine, 6-mercaptopurine or oral methotrexate) may be enrolled provided that chemotherapy is discontinued at least 1 week or 5 half-lives (whichever is shorter) prior to apheresis.~Subjects receiving steroid therapy at physiologic replacement doses (≤5 mg/day of prednisone or equivalent doses of other corticosteroids) only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis;~For radiation therapy: Radiation therapy must have been completed at least 3 weeks prior to apheresis, with the exception that there is no time restriction if the volume of bone marrow treated is less than 10% and also the subject has measurable/evaluable disease outside the radiation port.~Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia)~Age 18 or older~Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2; or Karnofsky ≥ 60%~Normal Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)~ANC ≥ 1000/uL*~Platelet count ≥ 50,000/uL*~Absolute lymphocyte count ≥ 300/uL*~Adequate renal, hepatic, pulmonary and cardiac function defined as:~Creatinine ≤ 2 mg/dL or creatinine clearance ≥ 60 mL/min~Serum ALT or AST ≤ 5x ULN (Elevated ALT/AST associated with leukemia or lymphoma involvement of the liver will not disqualify a subject; only one value required for eligibility).~Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome.~Cardiac ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an ECHO, MUGA or Cardiac MRI [performed within 180 days or after most recent anthracycline based treatment or mediastinal radiation therapy (whichever is most recent)]~No clinically significant ECG findings~No clinically significant pleural effusion~Baseline oxygen saturation > 92% on room air * A subject will not be excluded because of cytopenia if it is felt by the investigator to be due to underlying leukemia/lymphoma.~Subjects with CNS involvement are eligible as long as there are no overt signs or symptoms that in the evaluation of the investigator would mask or interfere with the neurological assessment of toxicity.~Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)~Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative lymphodepletion regimen or 1 month after the last dose of NKTR_255, whichever is later.~Ability to give informed consent. Must be able to give informed consent. Subjects unable to give informed consent will not be eligible for this study.~=ELIGIBILITY TO RECEIVE NKTR-255=~Received a CD19/CD22 CAR-T infusion~No persisting grade ≥1 CRS or greater than grade 1 fever within 12 hours preceding NKTR-255 infusion~No grade 4 CRS within 96 hours preceding NKTR-255 infusion~No persisting grade ≥ 2 neurotoxicity on the day of NKTR-255 infusion~No previous grade ≥ 3 neurotoxicity of > 48 hours duration at any time preceding NKTR-255 infusion~ANC ≥ 1000/µL~No intervention with tocilizumab and/or dexamethasone within 48 hours preceding NKTR-255 infusion~No active, serious, and uncontrolled infection(s)~No contraindications according to the PI's assessment~Life expectancy > 30 days~Exclusion Criteria:~History of other malignancy, unless disease free for at least 3 years. At the discretion of the Principal Investigator, subjects in remission for 1-2 years prior to enrollment may be deemed eligible after considering the nature of other malignancy, likelihood of recurrence during one year following CAR therapy, and impact of prior treatment on risk of CD19/CD22-CAR T cells. Subjects in remission <1 year are not eligible.~Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) is eligible.~Hormonal therapy in subjects in remission >1 year will be allowed.~Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.~Known history of infection with any of the following:~HIV~Hepatitis B (HBsAg positive)~Hepatitis C virus (anti-HCV positive) A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.~Presence of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicity.~History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment~Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment~History of severe immediate hypersensitivity reaction to any of the agents used in this study~Women who are pregnant or breastfeeding~In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.~Previous treatment with interleukin-2 or interleukin-15.~Confirmed diagnosis of relapsed/refractory biphenotypic BT cell ALL~Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/CD22 chimeric antigen receptor (CAR) T cells | Safety data will be analyzed per standard methods and interpreted descriptively for each dose cohort. Safety data will be summarized for each dose cohort separately and for all dose cohorts combined. Adverse events will be assessed using the CTCAE version 4.03 for type and severity of event. Serious Adverse Events will be summarized for each dose cohort and for all dose cohorts combined. Reasons for discontinuation of study therapy will be tabulated. | Up to 28 days |
| Maximum tolerated dose of CD19/CD22 chimeric antigen receptor (CAR) T cells defined as the dose level immediately below the level at which the enrollment is stopped due to a dose limiting toxicity | Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | Up to 28 days |
| Rate of successful manufacture and expansion of the CD19/CD22 chimeric antigen receptor (CAR) T cells to satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis | In addition to aiming to evaluate up to 6 subjects at a given dose level with respect to toxicity, the number of subjects which can successfully manufacture the targeted dose number will be determined. | Up to 15 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Will be assessed by dose cohort. | From the start of the preparative regimen until death, assessed for up to 15 years |
| Progression free survival | Will be assessed by dose cohort. | From the start of the preparative regimen until the documentation of disease progression or death due to any cause, whichever occurs first, assessed for up to 15 years |
| The ability to achieve a clinical response after administration of CD19/CD22 chimeric antigen receptor (CAR) T cells | Will be assessed by the Response Criteria for Lymphoma and the Response Criteria for Acute Lymphoblastic Leukemia. | Up to 15 years |
|
Cyclophosphamide, Fludarabine, Fludarabine phosphate, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs, Antirheumatic Agents, Antineoplastic Agents, Alkylating, Alkylating Agents, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Myeloablative Agonists, Antimetabolites, Antineoplastic, Antimetabolites
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (CD19/CD22 CAR T cells, chemotherapy, NKTR-255)<br>Patients receive cyclophosphamide IV over 60 minutes and fludarabine phosphate IV over 30 minutes on days -5 to -3. Patients then receive CD19/CD22 CAR T cells IV over 10-20 minutes on day 0. On Day 14 after CAR-T, eligible patients will be given NKTR-255 IV over 30 minutes, and it will be repeated every 28 days for up to 6 cycles. Patients that benefited from the first dose of CD19/CD22 CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22 CAR T cells. | Biological: Chimeric Antigen Receptor T-Cell Therapy<br>* Given CD19/CD22 CAR T cells IV<br>* Other names: CAR T-cell therapy;Drug: Cyclophosphamide<br>* Given IV<br>* Other names: WR- 138719;Drug: Fludarabine Phosphate<br>* Given IV<br>* Other names: SH T 586;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: NKTR-255<br>* Given IV<br>|
|
CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells With or Without NKTR-255 in Adults With Recurrent or Refractory B Cell Malignancies
Study Overview
=================
Brief Summary
-----------------
This phase I trial studies the side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy and NKTR-255, and to see how well they work in treating patients with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on diffuse large B-cell lymphoma and B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. NKTR-255 is an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer. Giving CD19/CD22-CAR T cells and chemotherapy in combination with NKTR-255 may work better in treating patients with diffuse large B-cell lymphoma or B acute lymphoblastic leukemia.
Detailed Description
-----------------
PRIMARY OBJECTIVES: I. Determine the feasibility of producing CD19/CD22 CAR T cells meeting the established release criteria. II. Assess the safety of administering escalating doses of autologous CD19/CD22 CAR T cells that meet established release specifications in adults with B cell hematologic malignancies following a cyclophosphamide/fludarabine conditioning regimen. III. Assess the safety and feasibility of administering repeated doses of NKTR-255 intravenously after CD19/CD22-CAR T cell infusions in adults with ALL using a dose escalation design. IV. Determine the recommended phase 2 dose (RP2D) of NKTR-255 when administered following CD19/CD22-CAR T cell infusion in adults with ALL SECONDARY OBJECTIVES: I. Evaluate the ability of CD19/CD22 CAR T cells to mediate clinical activity in adults with DLBCL and adults with ALL. II. Characterize the pharmacokinetics (PK) of NKTR-255 when administered post CD19/CD22 CAR T cell infusion. III. Explore the rate of relapse, progression free survival (PFS) and overall survival (OS) in subjects receiving CD19/CD22 CAR T cells, followed by up to 6 cycles of NKTR-255
Official Title
-----------------
Phase 1 Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells With or Without NKTR-255 in Adults With Recurrent or Refractory B Cell Malignancies
Conditions
-----------------
B Acute Lymphoblastic Leukemia, CD19 Positive, Minimal Residual Disease, Philadelphia Chromosome Positive
Intervention / Treatment
-----------------
* Biological: Chimeric Antigen Receptor T-Cell Therapy
* Drug: Cyclophosphamide
* Drug: Fludarabine Phosphate
* Other: Laboratory Biomarker Analysis
* Other: Questionnaire Administration
* Drug: NKTR-255
Participation Criteria
=================
Eligibility Criteria
-----------------
For B acute lymphoblastic leukemia (ALL) Confirmed diagnosis of relapsed or refractory B-cell ALL of one of the following types: Chemotherapy refractory disease in subjects with B-ALL, defined as progression or stable disease after one line of therapy. Recurrence of disease after achieving CR. Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, FISH, or next generation sequencing) require verification of MRD positivity on two occasions at least 4 weeks apart. Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed after receiving a tyrosine kinase inhibitor (TKI). Subjects with recurrence of isolated CNS relapse after achieving complete remission (CR); if relapsed with MRD, will require verification of MRD positivity on two occasions at least 4 weeks apart. CD19 positive expression- CD19 expression is required at any time since diagnosis. If patient has received anti-CD19 targeted therapy (i.e. Blinatumomab or CD19-CAR T cells), then CD19 expression must be subsequently demonstrated. CD19 expression may be detected by immunohistochemistry or by flow cytometry. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each subject. In general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples. Subjects who have undergone autologous SCT with disease progression or relapse following SCT are eligible. Subjects who have undergone allogeneic SCT will be eligible if, in addition to meeting other eligibility criteria, they have elelino evidence of GVHD and have been without immunosuppressive agents for at least 30 days. Subjects who have undergone prior anti-CD19 or anti-CD22 CAR therapy must be at least 30 days post CAR infusion and may not have eficence of persistnce of CAR T cells in blood smples (circulating levels of genetically modified cels of >/= 5% by flow cytometry. Must have evaluable or measurable disease. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives. Exceptions: There is no time restriction with regard to prior intrathecal chemotherapy (incl. steroids) provided there is complete recovery from any acute toxic effects; Subjects who are on standard ALL maintenance type chemotherapy (vincristine, 6-mercaptopurine or oral methotrexate) may be enrolled provided that chemotherapy is discontinued at least 1 week or 5 half-lives (whichever is shorter) prior to apheresis. Subjects receiving steroid therapy at physiologic replacement doses (≤5 mg/day of prednisone or equivalent doses of other corticosteroids) only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis; For radiation therapy: Radiation therapy must have been completed at least 3 weeks prior to apheresis, with the exception that there is no time restriction if the volume of bone marrow treated is less than 10% and also the subject has measurable/evaluable disease outside the radiation port. Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia) Age 18 or older Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2; or Karnofsky ≥ 60% Normal Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion) ANC ≥ 1000/uL* Platelet count ≥ 50,000/uL* Absolute lymphocyte count ≥ 300/uL* Adequate renal, hepatic, pulmonary and cardiac function defined as: Creatinine ≤ 2 mg/dL or creatinine clearance ≥ 60 mL/min Serum ALT or AST ≤ 5x ULN (Elevated ALT/AST associated with leukemia or lymphoma involvement of the liver will not disqualify a subject; only one value required for eligibility). Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome. Cardiac ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an ECHO, MUGA or Cardiac MRI [performed within 180 days or after most recent anthracycline based treatment or mediastinal radiation therapy (whichever is most recent)] No clinically significant ECG findings No clinically significant pleural effusion Baseline oxygen saturation > 92% on room air * A subject will not be excluded because of cytopenia if it is felt by the investigator to be due to underlying leukemia/lymphoma. Subjects with CNS involvement are eligible as long as there are no overt signs or symptoms that in the evaluation of the investigator would mask or interfere with the neurological assessment of toxicity. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential) Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative lymphodepletion regimen or 1 month after the last dose of NKTR_255, whichever is later. Ability to give informed consent. Must be able to give informed consent. Subjects unable to give informed consent will not be eligible for this study. =ELIGIBILITY TO RECEIVE NKTR-255= Received a CD19/CD22 CAR-T infusion No persisting grade ≥1 CRS or greater than grade 1 fever within 12 hours preceding NKTR-255 infusion No grade 4 CRS within 96 hours preceding NKTR-255 infusion No persisting grade ≥ 2 neurotoxicity on the day of NKTR-255 infusion No previous grade ≥ 3 neurotoxicity of > 48 hours duration at any time preceding NKTR-255 infusion ANC ≥ 1000/µL No intervention with tocilizumab and/or dexamethasone within 48 hours preceding NKTR-255 infusion No active, serious, and uncontrolled infection(s) No contraindications according to the PI's assessment Life expectancy > 30 days Exclusion Criteria: History of other malignancy, unless disease free for at least 3 years. At the discretion of the Principal Investigator, subjects in remission for 1-2 years prior to enrollment may be deemed eligible after considering the nature of other malignancy, likelihood of recurrence during one year following CAR therapy, and impact of prior treatment on risk of CD19/CD22-CAR T cells. Subjects in remission <1 year are not eligible. Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) is eligible. Hormonal therapy in subjects in remission >1 year will be allowed. Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment. Known history of infection with any of the following: HIV Hepatitis B (HBsAg positive) Hepatitis C virus (anti-HCV positive) A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing. Presence of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicity. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment History of severe immediate hypersensitivity reaction to any of the agents used in this study Women who are pregnant or breastfeeding In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation. Previous treatment with interleukin-2 or interleukin-15. Confirmed diagnosis of relapsed/refractory biphenotypic BT cell ALL Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (CD19/CD22 CAR T cells, chemotherapy, NKTR-255)<br>Patients receive cyclophosphamide IV over 60 minutes and fludarabine phosphate IV over 30 minutes on days -5 to -3. Patients then receive CD19/CD22 CAR T cells IV over 10-20 minutes on day 0. On Day 14 after CAR-T, eligible patients will be given NKTR-255 IV over 30 minutes, and it will be repeated every 28 days for up to 6 cycles. Patients that benefited from the first dose of CD19/CD22 CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22 CAR T cells. | Biological: Chimeric Antigen Receptor T-Cell Therapy<br>* Given CD19/CD22 CAR T cells IV<br>* Other names: CAR T-cell therapy;Drug: Cyclophosphamide<br>* Given IV<br>* Other names: WR- 138719;Drug: Fludarabine Phosphate<br>* Given IV<br>* Other names: SH T 586;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>Drug: NKTR-255<br>* Given IV<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/CD22 chimeric antigen receptor (CAR) T cells | Safety data will be analyzed per standard methods and interpreted descriptively for each dose cohort. Safety data will be summarized for each dose cohort separately and for all dose cohorts combined. Adverse events will be assessed using the CTCAE version 4.03 for type and severity of event. Serious Adverse Events will be summarized for each dose cohort and for all dose cohorts combined. Reasons for discontinuation of study therapy will be tabulated. | Up to 28 days |
| Maximum tolerated dose of CD19/CD22 chimeric antigen receptor (CAR) T cells defined as the dose level immediately below the level at which the enrollment is stopped due to a dose limiting toxicity | Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | Up to 28 days |
| Rate of successful manufacture and expansion of the CD19/CD22 chimeric antigen receptor (CAR) T cells to satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis | In addition to aiming to evaluate up to 6 subjects at a given dose level with respect to toxicity, the number of subjects which can successfully manufacture the targeted dose number will be determined. | Up to 15 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Will be assessed by dose cohort. | From the start of the preparative regimen until death, assessed for up to 15 years |
| Progression free survival | Will be assessed by dose cohort. | From the start of the preparative regimen until the documentation of disease progression or death due to any cause, whichever occurs first, assessed for up to 15 years |
| The ability to achieve a clinical response after administration of CD19/CD22 chimeric antigen receptor (CAR) T cells | Will be assessed by the Response Criteria for Lymphoma and the Response Criteria for Acute Lymphoblastic Leukemia. | Up to 15 years |
|
|
NCT01717365
|
Psychometric / Validation Study
|
Data for the study will be collected from therapist across the world. The therapists will share data they have already compiled from their caseload. Data will be stripped of all personal identifiers and personal health information. The TWU SCOPE research team has no contact with clients whose assessment data is being shared for secondary analysis or clinical data repository. For educational and training purposes clients can be videotaped by the therapist who will obtain consent and/or assent from the client. Not every client will be videotaped. The subjects from the data shared by the therapists are from the ages of 0-21, both male and female, and of any ethnicity. The total amount of data collected from all participating therapists will be 500 pieces.
|
Therapists will be recruited by a TWU SCOPE research team member via email. Therapists who wish to participate will send a data sharing letter to the PI of the study. Once the TWU SCOPE research team has received the data sharing letter, a clinical data packet will then be distributed to the therapist through the U.S. mail or an email will be sent containing a web address link to http://www.myweb.twu.edu/~ttioseco for access to the clinical data packet via the internet. Those therapists who collect ten pieces or more of de-identified data and send them to the TWU SCOPE research team will receive an incentive in the form of a gift card.~Flow Chart of Research Study Process Collaborators (share new de-identified data) → databank (new de-identified data input) → data analysis (analysis of new and old de-identified data) → publication/presentation~No risks are involved because data collected is without any personal identifiers.
|
SCOPE: A Psychometric Study
|
To Determine the Psychometric Properties of the Short Child Occupational Profile
|
Inclusion Criteria:~Subjects receiving therapy from participating therapists.~Exclusion Criteria:~Age over 21.
| null |
21 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the psychometric properties of the Short Child Occupational Profile Validate SCOPE | To determine the psychometric properties of the Short Child Occupational Profile (SCOPE) and validate the SCOPE. | 36 months |
|
SCOPE
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| OTs<br>Occupational therapists | |
|
Psychometric / Validation Study
Study Overview
=================
Brief Summary
-----------------
Data for the study will be collected from therapist across the world. The therapists will share data they have already compiled from their caseload. Data will be stripped of all personal identifiers and personal health information. The TWU SCOPE research team has no contact with clients whose assessment data is being shared for secondary analysis or clinical data repository. For educational and training purposes clients can be videotaped by the therapist who will obtain consent and/or assent from the client. Not every client will be videotaped. The subjects from the data shared by the therapists are from the ages of 0-21, both male and female, and of any ethnicity. The total amount of data collected from all participating therapists will be 500 pieces.
Detailed Description
-----------------
Therapists will be recruited by a TWU SCOPE research team member via email. Therapists who wish to participate will send a data sharing letter to the PI of the study. Once the TWU SCOPE research team has received the data sharing letter, a clinical data packet will then be distributed to the therapist through the U.S. mail or an email will be sent containing a web address link to http://www.myweb.twu.edu/ ttioseco for access to the clinical data packet via the internet. Those therapists who collect ten pieces or more of de-identified data and send them to the TWU SCOPE research team will receive an incentive in the form of a gift card. Flow Chart of Research Study Process Collaborators (share new de-identified data) → databank (new de-identified data input) → data analysis (analysis of new and old de-identified data) → publication/presentation No risks are involved because data collected is without any personal identifiers.
Official Title
-----------------
SCOPE: A Psychometric Study
Conditions
-----------------
To Determine the Psychometric Properties of the Short Child Occupational Profile
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects receiving therapy from participating therapists. Exclusion Criteria: Age over 21.
Ages Eligible for Study
-----------------
Maximum Age: 21 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| OTs<br>Occupational therapists | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the psychometric properties of the Short Child Occupational Profile Validate SCOPE | To determine the psychometric properties of the Short Child Occupational Profile (SCOPE) and validate the SCOPE. | 36 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SCOPE
|
||||
NCT00930007
|
Sleep-wake Changes of Luteinizing Hormone Frequency in Pubertal Girls With and Without High Testosterone
|
The purpose of this study is to determine whether sleep-wake changes of luteinizing hormone pulse frequency are different in early pubertal girls with high testosterone levels compared to early pubertal girls with normal testosterone levels.
|
During early puberty, luteinizing hormone (LH) pulse frequency normally increases during sleep. In contrast, preliminary data suggest that obese girls (who have high testosterone levels in general) demonstrate low LH frequency during the day and night during early puberty; but at mid puberty rapidly transition to a high LH frequency during the day and night. We hypothesize that in early pubertal girls with high testosterone levels, overnight increases of LH frequency are less prominent than those observed in early pubertal girls with normal testosterone levels. We will assess this using a frequent sampling protocol for assessment of LH pulse frequency (with sampling occurring while awake and while asleep) in early pubertal girls with and without high testosterone levels. Sleep will be formally evaluated.
|
Comparison of Sleep-wake LH Frequency in Peripubertal Girls With and Without Hyperandrogenemia
|
Hyperandrogenism
|
* Other: Blood sampling
|
Inclusion Criteria:~Early to midpubertal girls (late Tanner 1 [i.e., estradiol > 20 pg/ml] to Tanner 3)~Premenarcheal~Approximate ages, 8-15 years~Exclusion Criteria:~BMI-for-age < 5th percentile~Inability to comprehend what will be done during the study or why it will be done~Being a study of GnRH pulse regulation in adolescent girls with and without HA, boys are excluded~Obesity associated with a diagnosed (genetic) syndrome (e.g., Prader-Willi syndrome, leptin deficiency), obesity related to medications (e.g., glucocorticoids), etc.~Pregnancy or lactation~Virilization~Total testosterone > 150 ng/dl (confirmed on repeat)~DHEAS > upper limit of age-appropriate normal range (confirmed on repeat) (mild elevations may be seen in adolescent HA, and elevations < 1.5 times the age-appropriate upper limit of normal will be accepted in such girls)~Follicular phase 17-hydroxyprogesterone > 250 ng/dl (for girls < 12 years old) or > 300 ng/dl (for girls 12 and older) (confirmed on repeat), which suggests the possibility of congenital adrenal hyperplasia. NOTE: If an elevated follicular 17-hydroxyprogesterone is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation~History of premature adrenarche (i.e., appearance of pubic and/or axillary hair before age 8)~A previous diagnosis of diabetes~Fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6.5% (confirmed on repeat)~Abnormal TSH (confirmed on repeat) (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded)~Abnormal prolactin (confirmed on repeat) (mild elevations may be seen in HA girls, and elevations < 1.5 times the upper limit of normal will be accepted in this group)~Evidence of Cushing's syndrome by history or physical exam (e.g., history of impaired growth in children, striae)~Hematocrit < 36% and hemoglobin < 12 g/dl (confirmed on repeat)~Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.)~Persistent liver test abnormalities (confirmed on repeat), with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome~Persistently abnormal sodium, potassium, or elevated creatinine concentration (confirmed on repeat)~Bicarbonate concentrations < 20 or > 30 (confirmed on repeat)~No medications known to affect the reproductive system, glucose metabolism, lipid metabolism, or blood pressure can be taken in the 3 months prior to the first inpatient GCRC study (or in the 2 months prior to screening)~Such medications include oral contraceptive pills, progestins, metformin, glucocorticoids, psychotropics, and sympathomimetics/stimulants (e.g., methylphenidate)~Patients taking restricted medications will be excluded unless written permission (for the subjects to discontinue the medication) is received from the subject's physician~Weight < 22 kg is an absolute exclusion criterion (to ensure safe blood withdrawal)
|
8 Years
|
15 Years
|
Female
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Luteinizing hormone pulse frequency (while awake and while asleep) | | Baseline (time zero) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progesterone concentration | | Baseline (time zero) |
| Estradiol concentration | | Baseline (time zero) |
| Testosterone concentrations | | Baseline (time zero) |
| Luteinizing hormone amplitude | | Baseline (time zero) |
| Sleep stage parameters | | Baseline (time zero) |
|
Luteinizing hormone, Puberty
|
Hyperandrogenism, 46, XX Disorders of Sex Development, Disorders of Sex Development, Urogenital Abnormalities, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Adrenogenital Syndrome, Male Urogenital Diseases, Congenital Abnormalities, Gonadal Disorders, Endocrine System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hyperandrogenemic<br>Girls with elevated free testosterone concentrations | Other: Blood sampling<br>* Blood sampling for later hormone measurements<br>|
| Controls<br>Girls with normal free testosterone concentrations | Other: Blood sampling<br>* Blood sampling for later hormone measurements<br>|
|
Sleep-wake Changes of Luteinizing Hormone Frequency in Pubertal Girls With and Without High Testosterone
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether sleep-wake changes of luteinizing hormone pulse frequency are different in early pubertal girls with high testosterone levels compared to early pubertal girls with normal testosterone levels.
Detailed Description
-----------------
During early puberty, luteinizing hormone (LH) pulse frequency normally increases during sleep. In contrast, preliminary data suggest that obese girls (who have high testosterone levels in general) demonstrate low LH frequency during the day and night during early puberty; but at mid puberty rapidly transition to a high LH frequency during the day and night. We hypothesize that in early pubertal girls with high testosterone levels, overnight increases of LH frequency are less prominent than those observed in early pubertal girls with normal testosterone levels. We will assess this using a frequent sampling protocol for assessment of LH pulse frequency (with sampling occurring while awake and while asleep) in early pubertal girls with and without high testosterone levels. Sleep will be formally evaluated.
Official Title
-----------------
Comparison of Sleep-wake LH Frequency in Peripubertal Girls With and Without Hyperandrogenemia
Conditions
-----------------
Hyperandrogenism
Intervention / Treatment
-----------------
* Other: Blood sampling
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Early to midpubertal girls (late Tanner 1 [i.e., estradiol > 20 pg/ml] to Tanner 3) Premenarcheal Approximate ages, 8-15 years Exclusion Criteria: BMI-for-age < 5th percentile Inability to comprehend what will be done during the study or why it will be done Being a study of GnRH pulse regulation in adolescent girls with and without HA, boys are excluded Obesity associated with a diagnosed (genetic) syndrome (e.g., Prader-Willi syndrome, leptin deficiency), obesity related to medications (e.g., glucocorticoids), etc. Pregnancy or lactation Virilization Total testosterone > 150 ng/dl (confirmed on repeat) DHEAS > upper limit of age-appropriate normal range (confirmed on repeat) (mild elevations may be seen in adolescent HA, and elevations < 1.5 times the age-appropriate upper limit of normal will be accepted in such girls) Follicular phase 17-hydroxyprogesterone > 250 ng/dl (for girls < 12 years old) or > 300 ng/dl (for girls 12 and older) (confirmed on repeat), which suggests the possibility of congenital adrenal hyperplasia. NOTE: If an elevated follicular 17-hydroxyprogesterone is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation History of premature adrenarche (i.e., appearance of pubic and/or axillary hair before age 8) A previous diagnosis of diabetes Fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6.5% (confirmed on repeat) Abnormal TSH (confirmed on repeat) (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded) Abnormal prolactin (confirmed on repeat) (mild elevations may be seen in HA girls, and elevations < 1.5 times the upper limit of normal will be accepted in this group) Evidence of Cushing's syndrome by history or physical exam (e.g., history of impaired growth in children, striae) Hematocrit < 36% and hemoglobin < 12 g/dl (confirmed on repeat) Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.) Persistent liver test abnormalities (confirmed on repeat), with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome Persistently abnormal sodium, potassium, or elevated creatinine concentration (confirmed on repeat) Bicarbonate concentrations < 20 or > 30 (confirmed on repeat) No medications known to affect the reproductive system, glucose metabolism, lipid metabolism, or blood pressure can be taken in the 3 months prior to the first inpatient GCRC study (or in the 2 months prior to screening) Such medications include oral contraceptive pills, progestins, metformin, glucocorticoids, psychotropics, and sympathomimetics/stimulants (e.g., methylphenidate) Patients taking restricted medications will be excluded unless written permission (for the subjects to discontinue the medication) is received from the subject's physician Weight < 22 kg is an absolute exclusion criterion (to ensure safe blood withdrawal)
Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 15 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hyperandrogenemic<br>Girls with elevated free testosterone concentrations | Other: Blood sampling<br>* Blood sampling for later hormone measurements<br>|
| Controls<br>Girls with normal free testosterone concentrations | Other: Blood sampling<br>* Blood sampling for later hormone measurements<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Luteinizing hormone pulse frequency (while awake and while asleep) | | Baseline (time zero) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progesterone concentration | | Baseline (time zero) |
| Estradiol concentration | | Baseline (time zero) |
| Testosterone concentrations | | Baseline (time zero) |
| Luteinizing hormone amplitude | | Baseline (time zero) |
| Sleep stage parameters | | Baseline (time zero) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Luteinizing hormone, Puberty
|
|
NCT00122993
|
Worksite Program to Prevent Weight Gain Among Bus Drivers
|
The purpose of this study is to implement and evaluate a two-year multi-component environmental intervention to prevent weight gain among city bus drivers at four bus garages.~It is hypothesized that transit employees in the intervention garages will gain less weight compared to the transit employees in the control garages.
|
BACKGROUND:~Environmental influences that support less healthful food choices and sedentary behaviors have contributed to the epidemic increase in overweight and obesity among U.S. adults. Worksite settings are an effective channel through which to reach adults with interventions designed to prevent excess weight gain and obesity.~DESIGN NARRATIVE:~This study will implement and evaluate a multi-component environmental intervention to prevent excess weight gain among 1200 bus drivers working in four garages in a major metropolitan area. Four garages will be randomized to the intervention or control group for a two-year period. The environmental interventions are based on a social ecological framework and target four worksite environmental areas: 1) food availability and incentives; 2) physical activity opportunities and incentives; 3) the social environment; and 4) media/promotion related to health food choices, physical activity, and body weight.
|
Worksite Environmental Interventions for Weight Control
|
Obesity, Cardiovascular Diseases, Heart Diseases
|
* Behavioral: Healthful eating and food choices behavior change programs and changes in worksite food availability and prices
* Behavioral: Physical Activity
* Behavioral: Environment
|
Inclusion Criteria:~Employed as a bus driver~Exclusion criteria:~Not employed as a bus operator at one of the four participating garages
|
18 Years
|
70 Years
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | | Measured at Year 2 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in energy intake and physical activity | | Measured at Year 2 |
| Health claims cost | | Measured at Year 2 |
|
Heart Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Multi-component environmental intervention to prevent excess weight gain among bus drivers | Behavioral: Healthful eating and food choices behavior change programs and changes in worksite food availability and prices<br>* Food choices and eating behavior programs and environmental changes will be implemented for 18 months in intervention garages.<br>Behavioral: Physical Activity<br>* Physical activity programs are offered at the intervention garages for an 18 month period.<br>Behavioral: Environment<br>* Changes in the food and physical activity environment are made for an 18 month period in intervention garages. These include improving the healthfulness of the foods available in vending machines, and improving the fitness rooms at the garages.<br>|
| No Intervention: 2<br>Control group | |
|
Worksite Program to Prevent Weight Gain Among Bus Drivers
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to implement and evaluate a two-year multi-component environmental intervention to prevent weight gain among city bus drivers at four bus garages. It is hypothesized that transit employees in the intervention garages will gain less weight compared to the transit employees in the control garages.
Detailed Description
-----------------
BACKGROUND: Environmental influences that support less healthful food choices and sedentary behaviors have contributed to the epidemic increase in overweight and obesity among U.S. adults. Worksite settings are an effective channel through which to reach adults with interventions designed to prevent excess weight gain and obesity. DESIGN NARRATIVE: This study will implement and evaluate a multi-component environmental intervention to prevent excess weight gain among 1200 bus drivers working in four garages in a major metropolitan area. Four garages will be randomized to the intervention or control group for a two-year period. The environmental interventions are based on a social ecological framework and target four worksite environmental areas: 1) food availability and incentives; 2) physical activity opportunities and incentives; 3) the social environment; and 4) media/promotion related to health food choices, physical activity, and body weight.
Official Title
-----------------
Worksite Environmental Interventions for Weight Control
Conditions
-----------------
Obesity, Cardiovascular Diseases, Heart Diseases
Intervention / Treatment
-----------------
* Behavioral: Healthful eating and food choices behavior change programs and changes in worksite food availability and prices
* Behavioral: Physical Activity
* Behavioral: Environment
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Employed as a bus driver Exclusion criteria: Not employed as a bus operator at one of the four participating garages
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Multi-component environmental intervention to prevent excess weight gain among bus drivers | Behavioral: Healthful eating and food choices behavior change programs and changes in worksite food availability and prices<br>* Food choices and eating behavior programs and environmental changes will be implemented for 18 months in intervention garages.<br>Behavioral: Physical Activity<br>* Physical activity programs are offered at the intervention garages for an 18 month period.<br>Behavioral: Environment<br>* Changes in the food and physical activity environment are made for an 18 month period in intervention garages. These include improving the healthfulness of the foods available in vending machines, and improving the fitness rooms at the garages.<br>|
| No Intervention: 2<br>Control group | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | | Measured at Year 2 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in energy intake and physical activity | | Measured at Year 2 |
| Health claims cost | | Measured at Year 2 |
|
|
NCT02856399
|
Long-term Effects of Methadone for Cancer Pain
|
The methadone is an useful opioid for the cancer pain treatment, mostly used in second or last line during the opioid rotation. The Methadone had an anti-MNDA effect, and clinicians agree that the methadone could have an effect in neuropathic cancer pain. During a previous study the investigators find that the pain was still improving after the week 2, but they had only a small number of patients still included at this stage and they cannot conclude.~The investigators decide to follow up systematically all the patients undergoing a methadone treatment for cancer pain, at day 28, to study the hypothesis about the long-term pain improvement.
|
Long-term Effects of Methadone for Cancer Pain
|
Cancer Pain
|
Inclusion Criteria:~Patients with t methadone for cancer pain in opioid rotation~Able to fill the questionnaire~Performance status (PS) from 0 to 2~Exclusion Criteria:~Patients PS 3~Unable to sign the informed consent
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between EVA pain score at Day 28 and Day 0 | long-term effects of methadone for cancer pain | pain score measure at Day 0 and Day 28 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in score of neuropathic pain intensity NPSI | | Day 0 and Day 28 |
| Change in depression and anxiety score HADS | | Day 0 and Day 28 |
| Change in quality of life score QOL C30 | | Day 0 and Day 28 |
| Side effect record | | up to Day 28 |
|
methadone, cancer pain, long term effect
|
Cancer Pain, Pain, Neurologic Manifestations
|
Long-term Effects of Methadone for Cancer Pain
Study Overview
=================
Brief Summary
-----------------
The methadone is an useful opioid for the cancer pain treatment, mostly used in second or last line during the opioid rotation. The Methadone had an anti-MNDA effect, and clinicians agree that the methadone could have an effect in neuropathic cancer pain. During a previous study the investigators find that the pain was still improving after the week 2, but they had only a small number of patients still included at this stage and they cannot conclude. The investigators decide to follow up systematically all the patients undergoing a methadone treatment for cancer pain, at day 28, to study the hypothesis about the long-term pain improvement.
Official Title
-----------------
Long-term Effects of Methadone for Cancer Pain
Conditions
-----------------
Cancer Pain
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with t methadone for cancer pain in opioid rotation Able to fill the questionnaire Performance status (PS) from 0 to 2 Exclusion Criteria: Patients PS 3 Unable to sign the informed consent
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between EVA pain score at Day 28 and Day 0 | long-term effects of methadone for cancer pain | pain score measure at Day 0 and Day 28 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in score of neuropathic pain intensity NPSI | | Day 0 and Day 28 |
| Change in depression and anxiety score HADS | | Day 0 and Day 28 |
| Change in quality of life score QOL C30 | | Day 0 and Day 28 |
| Side effect record | | up to Day 28 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
methadone, cancer pain, long term effect
|
||||
NCT01276236
|
Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)
|
The purpose of this pilot study is to determine whether Maraviroc is effective in the treatment of Kaposi's Sarcoma (KS), when it does not remit with standard antiretroviral drug therapy.
|
Although the advent of antiretroviral therapy (ART) may have greatly decreased the incidence of Kaposi's Sarcoma (KS) in resource rich settings, KS continues to be the most prevalent AIDS-defining malignancy in the world and carries with it significant morbidity and mortality. Indeed, in a recent epidemiological study examining cancers in Kampala, Uganda, KS was found to be second only to prostate cancer in terms of incidence rates.~There is growing evidence that C-C chemokine receptor 5 (CCR5) may be involved in the pathogenesis of KS. Kaposi's Sarcoma-associated Herpes Virus (KSHV), an agent found as necessary for KS pathogenesis, encodes viral macrophage inflammatory proteins or vMIP. vMIP-I and vMIP-II have been found to be ligands for chemokine receptors, and in particular the CCR5 receptor [5, 6], suggesting a potential role in the inflammatory process needed for KS pathogenesis. Further, vMIP-I induces Ca(2+) mobilization in monocytes expressing CCR5, suggesting an agonistic relationship between vMIP-I and the CCR5 receptor. In addition, vMIP has been found to be proangiogenic when expressed in endothelial cells, a key feature of KS tumor survival. As well, CCR5 has been found to be significantly increased in T cells populations of KS patients (from a preliminary study), and in 2 double-blind, placebo-controlled phase 3 studies in which a total of 1049 patients received the randomly assigned drug MVC, there was a trend revealing a lower incidence of KS in MVC arms vs placebo (0.36% vs 1.43%). This agonistic binding relationship between protein vMIP and CCR5, the proangiogenic activity associated with vMIP, the increased expression of CCR5 in KS, and trend towards lower incidence of KS when patients are taking MVC, suggest CCR5 may play an important role in KS pathogenesis. This involvement of CCR5 in KS pathogenesis implies that MVC may function as a potential therapeutic for KS. To date, there have been no studies examining the effect of MVC on KS.~There is a need for therapeutic development for KS. Standard of care for KS involves initiation or optimization of antiretroviral therapy. A significant proportion of KS cases do not respond to ART alone, with non-response rates ranging from 25-55%, with response times averaging 9 or more months depending on which patient series is identified. In severe or in cases of KS unresponsive to ART, standard of care involves systemic chemotherapy with liposomal doxorubicin, which is not without adverse reactions. Adverse reactions to liposomal doxorubicin include cardiac toxicity, nausea, vomiting, diarrhea, abdominal pain, fatigue, and patients may require pre-regime tests of varying costs, along with resources and time needed for intravenous infusion. Nonresponse rates for liposomal doxorubicin hover around 20%. Focal cases may be more amenable to radiation therapy or intralesional velban. However, radiation and intralesional therapies are limited to focal sites, require monitored visits and specialized care, can be given only in limited amounts, and carry various adverse effects. With these nonresponse rates, potential adverse reactions, and resources and time needed for therapeutic delivery, there are clear benefits proffered by an effective oral therapy requiring minimal monitoring, as is the case with MVC.~Maraviroc (MVC) is a member of a new class of antiretroviral compounds known as small molecule CCR5 antagonists that block R5 HIV entry into cluster of differentiation 4 (CD4) cells. Maraviroc has demonstrated selective and reversible binding to CCR5, as well as potent antiviral activity in vitro against a wide range of laboratory adapted strains of R5 HIV from Clades A, B, C, D, E, F, G, J and O. Maraviroc also retains in vitro antiviral activity against clinical isolates resistant to the existing drug classes, but has no activity against viruses that enter CD4+ cells using CXCR4. In vitro studies with approved antiretroviral medications indicate that there is no evidence of antagonism with any members of the other four classes of antiretroviral medications; nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non- nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) or fusion inhibitors.~Although there is growing evidence that CCR5, a potential therapeutic target, is involved in KS pathogenesis, to date there are no studies examining the effects of a CCR5 inhibitor such as Maraviroc (MVC) on KS. As such, the aim of this study is to examine the effect of Maraviroc, a CCR5 inhibitor, on KS.
|
Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)
|
Kaposi's Sarcoma
|
* Drug: Maraviroc
|
Inclusion Criteria:~HIV-1 infected, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.~Active biopsy confirmed KS~Screening plasma HIV RNA < 75 copies/mL~Patients have unremitting KS. Unremitting is defined as having active biopsy confirmed KS in spite of having had sustained HIV RNA < 75 copies/mL for 24 prior months. Isolated values that are detectable but < 500 copies will be allowed as long as the plasma HIV RNA levels before and after this time point are undetectable.~>90% adherence to therapy within the preceding 30 days, as determined by self-report.~Both male and female subjects are eligible. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.~Ability and willingness of subject or legal guardian/representative to provide informed consent~Exclusion Criteria:~Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason.~Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.~Concurrent treatment with immunomodulatory drugs or therapies, or exposure to any immunomodulatory drug or therapy in past 16 weeks.~Prior exposure to CCR5 inhibitors~Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000 cells/mm3, hemoglobin < 8mg/dL, estimated creatinine clearance <40 mL/minute.~Elevated transaminases greater than 2.5 times the upper limit of normal.~Evidence of cirrhosis~Pregnant or breastfeeding women~Use of both Tenofovir and Didanosine in current antiretroviral therapy regimen.~Local therapy for any KS index lesion in preceding 60 days, unless lesion has clearly progressed with enlargement since the local therapy
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Decrease in Kaposi's Sarcoma (KS) Total Surface Area | To assess improvements in disease, up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions. The collective surface area of the marker lesions was evaluated over the course of the study for either an increase or decrease in the total surface area of lesions using the modified AIDS Clinical Trials Group (ACTG) Oncology Committee Staging Criteria. | Up to 96 weeks |
| Percent Change in KS Total Surface Area | Up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions and the the collective surface area of the marker lesions was evaluated over the course of the study. The percent decrease or increase in the total surface area of lesions was calculated from comparing measurements at baseline and through week 96, or at the last assessment if participant withdrew from the study prior to week 96. | Up to 96 weeks |
| Change in Edema Grade | The presence and extent of lower extremity edema was assessed and graded on a scale from 0 to 2 in patients with a higher grade indicating a greater level of edema using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS Adverse Events (AE) Grading Table), Version 1.0. Edema grade was recorded at baseline was compared with edema grades recorded at week 96, or at last assessment if participant withdrew from study prior to week 96 and an change in grade was calculated to examine whether or not a decrease in overall grade was observed. A negative value would indicate an overall decrease in the grade of lower extremity edema, and positive value would indicate an overall increase in lower extremity edema. | Up to 96 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Kaposi's Sarcoma-associated Herpesvirus (KSHV) Viral Load | Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load. | Up to 96 weeks |
| Percent Change in CCR5 Levels on CD4+ T-Cells | Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD4+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD4+ T-Cells | Up to 96 weeks |
| Percent Change in CCR5 Levels on CD8+ T-cells | Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD8+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD8+ T-Cells | Up to 96 weeks |
| Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Positive (DR-CD38+) T-cells | Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38 positive (DR-CD38+) T-cells | Up to 96 weeks |
| Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Negative (DR-CD38-) T-cells | Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38- T-cells | Up to 96 weeks |
|
CCR5, Kaposi's Sarcoma, Maraviroc, HIV
|
Maraviroc, HIV Fusion Inhibitors, Viral Fusion Protein Inhibitors, Molecular Mechanisms of Pharmacological Action, Anti-HIV Agents, Anti-Retroviral Agents, Antiviral Agents, Anti-Infective Agents, CCR5 Receptor Antagonists
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm (Maraviroc)<br>The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen. | Drug: Maraviroc<br>* FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks.~Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks.~Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.<br>* Other names: Selzentry(Celsentri outside US);|
|
Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)
Study Overview
=================
Brief Summary
-----------------
The purpose of this pilot study is to determine whether Maraviroc is effective in the treatment of Kaposi's Sarcoma (KS), when it does not remit with standard antiretroviral drug therapy.
Detailed Description
-----------------
Although the advent of antiretroviral therapy (ART) may have greatly decreased the incidence of Kaposi's Sarcoma (KS) in resource rich settings, KS continues to be the most prevalent AIDS-defining malignancy in the world and carries with it significant morbidity and mortality. Indeed, in a recent epidemiological study examining cancers in Kampala, Uganda, KS was found to be second only to prostate cancer in terms of incidence rates. There is growing evidence that C-C chemokine receptor 5 (CCR5) may be involved in the pathogenesis of KS. Kaposi's Sarcoma-associated Herpes Virus (KSHV), an agent found as necessary for KS pathogenesis, encodes viral macrophage inflammatory proteins or vMIP. vMIP-I and vMIP-II have been found to be ligands for chemokine receptors, and in particular the CCR5 receptor [5, 6], suggesting a potential role in the inflammatory process needed for KS pathogenesis. Further, vMIP-I induces Ca(2+) mobilization in monocytes expressing CCR5, suggesting an agonistic relationship between vMIP-I and the CCR5 receptor. In addition, vMIP has been found to be proangiogenic when expressed in endothelial cells, a key feature of KS tumor survival. As well, CCR5 has been found to be significantly increased in T cells populations of KS patients (from a preliminary study), and in 2 double-blind, placebo-controlled phase 3 studies in which a total of 1049 patients received the randomly assigned drug MVC, there was a trend revealing a lower incidence of KS in MVC arms vs placebo (0.36% vs 1.43%). This agonistic binding relationship between protein vMIP and CCR5, the proangiogenic activity associated with vMIP, the increased expression of CCR5 in KS, and trend towards lower incidence of KS when patients are taking MVC, suggest CCR5 may play an important role in KS pathogenesis. This involvement of CCR5 in KS pathogenesis implies that MVC may function as a potential therapeutic for KS. To date, there have been no studies examining the effect of MVC on KS. There is a need for therapeutic development for KS. Standard of care for KS involves initiation or optimization of antiretroviral therapy. A significant proportion of KS cases do not respond to ART alone, with non-response rates ranging from 25-55%, with response times averaging 9 or more months depending on which patient series is identified. In severe or in cases of KS unresponsive to ART, standard of care involves systemic chemotherapy with liposomal doxorubicin, which is not without adverse reactions. Adverse reactions to liposomal doxorubicin include cardiac toxicity, nausea, vomiting, diarrhea, abdominal pain, fatigue, and patients may require pre-regime tests of varying costs, along with resources and time needed for intravenous infusion. Nonresponse rates for liposomal doxorubicin hover around 20%. Focal cases may be more amenable to radiation therapy or intralesional velban. However, radiation and intralesional therapies are limited to focal sites, require monitored visits and specialized care, can be given only in limited amounts, and carry various adverse effects. With these nonresponse rates, potential adverse reactions, and resources and time needed for therapeutic delivery, there are clear benefits proffered by an effective oral therapy requiring minimal monitoring, as is the case with MVC. Maraviroc (MVC) is a member of a new class of antiretroviral compounds known as small molecule CCR5 antagonists that block R5 HIV entry into cluster of differentiation 4 (CD4) cells. Maraviroc has demonstrated selective and reversible binding to CCR5, as well as potent antiviral activity in vitro against a wide range of laboratory adapted strains of R5 HIV from Clades A, B, C, D, E, F, G, J and O. Maraviroc also retains in vitro antiviral activity against clinical isolates resistant to the existing drug classes, but has no activity against viruses that enter CD4+ cells using CXCR4. In vitro studies with approved antiretroviral medications indicate that there is no evidence of antagonism with any members of the other four classes of antiretroviral medications; nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non- nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) or fusion inhibitors. Although there is growing evidence that CCR5, a potential therapeutic target, is involved in KS pathogenesis, to date there are no studies examining the effects of a CCR5 inhibitor such as Maraviroc (MVC) on KS. As such, the aim of this study is to examine the effect of Maraviroc, a CCR5 inhibitor, on KS.
Official Title
-----------------
Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)
Conditions
-----------------
Kaposi's Sarcoma
Intervention / Treatment
-----------------
* Drug: Maraviroc
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HIV-1 infected, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test. Active biopsy confirmed KS Screening plasma HIV RNA < 75 copies/mL Patients have unremitting KS. Unremitting is defined as having active biopsy confirmed KS in spite of having had sustained HIV RNA < 75 copies/mL for 24 prior months. Isolated values that are detectable but < 500 copies will be allowed as long as the plasma HIV RNA levels before and after this time point are undetectable. >90% adherence to therapy within the preceding 30 days, as determined by self-report. Both male and female subjects are eligible. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period. Ability and willingness of subject or legal guardian/representative to provide informed consent Exclusion Criteria: Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason. Serious illness requiring hospitalization or parental antibiotics within preceding 3 months. Concurrent treatment with immunomodulatory drugs or therapies, or exposure to any immunomodulatory drug or therapy in past 16 weeks. Prior exposure to CCR5 inhibitors Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000 cells/mm3, hemoglobin < 8mg/dL, estimated creatinine clearance <40 mL/minute. Elevated transaminases greater than 2.5 times the upper limit of normal. Evidence of cirrhosis Pregnant or breastfeeding women Use of both Tenofovir and Didanosine in current antiretroviral therapy regimen. Local therapy for any KS index lesion in preceding 60 days, unless lesion has clearly progressed with enlargement since the local therapy
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm (Maraviroc)<br>The subjects in this arm will receive Maraviroc as treatment, while continuing their current antiretroviral medication regimen. | Drug: Maraviroc<br>* FDA Recommended dosing will be used in this study. Subjects on an efavirenz or etravirine-based regimen will be dosed at 600 mg orally, twice per day, for 96 weeks. Subjects on a ritonavir-boosted protease inhibitor based regimen (except for tipranavir/ritonavir) will be dosed at 150 mg orally, twice per day, for 96 weeks. Subjects that are on regimens that do not include etravirine, efavirenz, or ritonavir will be dosed at 300mg orally, twice per day, for 96 weeks. These doses are based on the recommendations from the company based on drug-drug interactions.<br>* Other names: Selzentry(Celsentri outside US);|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Decrease in Kaposi's Sarcoma (KS) Total Surface Area | To assess improvements in disease, up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions. The collective surface area of the marker lesions was evaluated over the course of the study for either an increase or decrease in the total surface area of lesions using the modified AIDS Clinical Trials Group (ACTG) Oncology Committee Staging Criteria. | Up to 96 weeks |
| Percent Change in KS Total Surface Area | Up to five bi-dimensionally measurable cutaneous KS lesions were selected as marker lesions and the the collective surface area of the marker lesions was evaluated over the course of the study. The percent decrease or increase in the total surface area of lesions was calculated from comparing measurements at baseline and through week 96, or at the last assessment if participant withdrew from the study prior to week 96. | Up to 96 weeks |
| Change in Edema Grade | The presence and extent of lower extremity edema was assessed and graded on a scale from 0 to 2 in patients with a higher grade indicating a greater level of edema using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS Adverse Events (AE) Grading Table), Version 1.0. Edema grade was recorded at baseline was compared with edema grades recorded at week 96, or at last assessment if participant withdrew from study prior to week 96 and an change in grade was calculated to examine whether or not a decrease in overall grade was observed. A negative value would indicate an overall decrease in the grade of lower extremity edema, and positive value would indicate an overall increase in lower extremity edema. | Up to 96 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Kaposi's Sarcoma-associated Herpesvirus (KSHV) Viral Load | Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load. | Up to 96 weeks |
| Percent Change in CCR5 Levels on CD4+ T-Cells | Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD4+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD4+ T-Cells | Up to 96 weeks |
| Percent Change in CCR5 Levels on CD8+ T-cells | Maraviroc works by binding to the C-C chemokine receptor 5 (CCR5) on T-cells and thereby blocking viral entry into CD8+ T-cells. Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CCR5 levels on CD8+ T-Cells | Up to 96 weeks |
| Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Positive (DR-CD38+) T-cells | Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38 positive (DR-CD38+) T-cells | Up to 96 weeks |
| Percent Change in CD69 Expression in a Subset of Double Negative DR-CD38 Negative (DR-CD38-) T-cells | Peripheral blood mononuclear cells (PBMC) were obtained from blood draws at each visit and T-cell immunophenotyping was performed from the baseline visit and final follow-up visit to determine the percent change in CD69 expression in a subset of double negative DR-CD38- T-cells | Up to 96 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CCR5, Kaposi's Sarcoma, Maraviroc, HIV
|
NCT04394572
|
Identification of New Diagnostic Protein Markers for Colorectal Cancer
|
The search for biochemical markers in patient's blood for non-invasive colorectal cancer diagnostic has not yielded satisfactory results to date. The search for blood in the stool by enzymatic techniques has certainly allowed the diminution of colorectal cancer mortality but its low sensitivity is still a disadvantage. The new immunological tests for search blood test in the stool are more sensitive and more specific but still insufficient. The originality of this project is based on the use of new technology developed in fundamental research based on the detection of circulating exosomes from tumor cells in the patient's serum. The detection of protein markers transported by tumor exosomes is original and innovative approach because it's still not considered in the literature. The use of innovative and non-invasive health technologies for the patient is an important factor in the care of patients in their health care journey. The non-invasive nature of the project could reduce the reticence of patients to participate in cancer screening.~The results expected from the study can have a direct impact on the management of patients suspected of having colon cancer and thus make it possible to optimize the earliness of their diagnosis.
|
In terms of frequency, colorectal cancer is the third most common cancer diagnosed in men and the second in women. Screening for colon and rectal cancer is based on the search for blood in the stool. The detection of occult bleeding is an indication for colonoscopy to find the origin of this bleeding. In this context, the search for biochemical markers in the blood of patients for diagnostic purposes has not yielded satisfactory results to date. Cancer cells, including colorectal cancer cells, release extracellular vesicles that contain proteins, mRNAs, DNA that can be transferred to neighboring cells but that also circulate through the blood stream and can modulate tumor progression and metastatic spread. These extracellular vesicles are of two types: exosomes (40 to 100 nm in diameter) formed by budding of endosome membranes and microvesicles (100 to 1000 nm in diameter) resulting from the budding of plasma membrane. Exosomes carry transmembrane proteins on their surface, called tetraspanins (CD9, CD63, CD81) but they also contain proteases involved in the degradation of the extracellular matrix, integrins involved in the tropism of metastases, and matrix macromolecules involved in the control of tumor invasion. The working hypothesis is that some of these exosomal proteins may be good diagnostic and / or prognostic markers for colorectal cancer. This project will aim to isolate exosomes from patient blood and to quantify previously cited proteins according to the accreditation criteria of clinical laboratory biology analyzes. For this purpose, exosomes will be isolated from sera of patients and their number, size and protein composition will be characterized. This project is an innovative and non-invasive prospective approach in the screening of protein markers for colorectal cancer diagnostic and / or prognostic.
|
Identification of New Diagnostic Protein Markers for Colorectal Cancer in Circulating Tumor Exosomes
|
Colorectal Cancer
|
* Biological: Blood sample
|
Inclusion Criteria:~Immunoassay for stool positive blood test or family screening~Patients seen in consultation for a colonoscopy~Patient who gave their consent for the study (signed consent form)~Patient affiliated to a health insurance plan~Exclusion Criteria:~History of other cancers (except for cervical cancer or basal cell carcinoma treated for curative purposes)~Patient under chemotherapy~Patients with a known familial mutation (APC, MSI, MYH)~Patients protected by law
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic performances of markers derived from circulating tumor exosomes in the context of colorectal cancer, focusing on macromolecules | Sensitivity and specificity of macromolecules | Day 1 |
| Diagnostic performances of markers derived from circulating tumor exosomes in the context of colorectal cancer, focusing on integrins | Sensitivity and specificity of integrins | Day 1 |
| Diagnostic performances of markers derived from circulating tumor exosomes in the context of colorectal cancer, focusing on metallo proteases | Sensitivity and specificity of metallo proteases | Day 1 |
|
exosome ; colon cancer; integrin; matrix metalloproteinases
|
Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| colorectal cancer<br>Patients with and without colorectal cancer | Biological: Blood sample<br>* All patients included in the study will have blood sample<br>|
|
Identification of New Diagnostic Protein Markers for Colorectal Cancer
Study Overview
=================
Brief Summary
-----------------
The search for biochemical markers in patient's blood for non-invasive colorectal cancer diagnostic has not yielded satisfactory results to date. The search for blood in the stool by enzymatic techniques has certainly allowed the diminution of colorectal cancer mortality but its low sensitivity is still a disadvantage. The new immunological tests for search blood test in the stool are more sensitive and more specific but still insufficient. The originality of this project is based on the use of new technology developed in fundamental research based on the detection of circulating exosomes from tumor cells in the patient's serum. The detection of protein markers transported by tumor exosomes is original and innovative approach because it's still not considered in the literature. The use of innovative and non-invasive health technologies for the patient is an important factor in the care of patients in their health care journey. The non-invasive nature of the project could reduce the reticence of patients to participate in cancer screening. The results expected from the study can have a direct impact on the management of patients suspected of having colon cancer and thus make it possible to optimize the earliness of their diagnosis.
Detailed Description
-----------------
In terms of frequency, colorectal cancer is the third most common cancer diagnosed in men and the second in women. Screening for colon and rectal cancer is based on the search for blood in the stool. The detection of occult bleeding is an indication for colonoscopy to find the origin of this bleeding. In this context, the search for biochemical markers in the blood of patients for diagnostic purposes has not yielded satisfactory results to date. Cancer cells, including colorectal cancer cells, release extracellular vesicles that contain proteins, mRNAs, DNA that can be transferred to neighboring cells but that also circulate through the blood stream and can modulate tumor progression and metastatic spread. These extracellular vesicles are of two types: exosomes (40 to 100 nm in diameter) formed by budding of endosome membranes and microvesicles (100 to 1000 nm in diameter) resulting from the budding of plasma membrane. Exosomes carry transmembrane proteins on their surface, called tetraspanins (CD9, CD63, CD81) but they also contain proteases involved in the degradation of the extracellular matrix, integrins involved in the tropism of metastases, and matrix macromolecules involved in the control of tumor invasion. The working hypothesis is that some of these exosomal proteins may be good diagnostic and / or prognostic markers for colorectal cancer. This project will aim to isolate exosomes from patient blood and to quantify previously cited proteins according to the accreditation criteria of clinical laboratory biology analyzes. For this purpose, exosomes will be isolated from sera of patients and their number, size and protein composition will be characterized. This project is an innovative and non-invasive prospective approach in the screening of protein markers for colorectal cancer diagnostic and / or prognostic.
Official Title
-----------------
Identification of New Diagnostic Protein Markers for Colorectal Cancer in Circulating Tumor Exosomes
Conditions
-----------------
Colorectal Cancer
Intervention / Treatment
-----------------
* Biological: Blood sample
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Immunoassay for stool positive blood test or family screening Patients seen in consultation for a colonoscopy Patient who gave their consent for the study (signed consent form) Patient affiliated to a health insurance plan Exclusion Criteria: History of other cancers (except for cervical cancer or basal cell carcinoma treated for curative purposes) Patient under chemotherapy Patients with a known familial mutation (APC, MSI, MYH) Patients protected by law
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| colorectal cancer<br>Patients with and without colorectal cancer | Biological: Blood sample<br>* All patients included in the study will have blood sample<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic performances of markers derived from circulating tumor exosomes in the context of colorectal cancer, focusing on macromolecules | Sensitivity and specificity of macromolecules | Day 1 |
| Diagnostic performances of markers derived from circulating tumor exosomes in the context of colorectal cancer, focusing on integrins | Sensitivity and specificity of integrins | Day 1 |
| Diagnostic performances of markers derived from circulating tumor exosomes in the context of colorectal cancer, focusing on metallo proteases | Sensitivity and specificity of metallo proteases | Day 1 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
exosome ; colon cancer; integrin; matrix metalloproteinases
|
||
NCT01655082
|
Nicotine Patch Safety Study
|
The purpose of this study is to evaluate the safety profile of a repeated application of a new transdermal patch compared to a reference product during 3 weeks, in a large population.
| null |
Smokers
|
* Drug: V0116 transdermal patch
* Drug: Nicotine transdermal patch
|
Inclusion Criteria:~Male or female aged more than 18 years~Regular smoker motivated to stop tobacco consumption~Current smoker of > or = 20 cigarettes/day and < or = 25 cigarettes/day or Fagerström score > or = 5 (for smokers between 10 to 20 cigarettes/day)~Exclusion Criteria:~Any visible skin disorder, abnormal skin pigmentation or other dermatologic disease which, in the opinion of the investigator would interfere with the assessment of the different parameters~Current or past serious chronic cardiovascular, renal, hepatic, gastrointestinal (including duodenal or gastric ulcer), endocrine, hematological, neuropsychiatric, immunosuppressive condition or allergic disease, myopathies, epileptic seizures, bleeding tendency, cancer~History of angina pectoris, myocardial infarction or stroke in the previous 3 months, coronary artery vasospasm, cardiac arrhythmia, acute stroke~Clinically relevant abnormal findings on the physical examination (e.g large scars on the application zone)
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Evaluation of local safety (number of subjects with skin irritation / number of subjects by score of adhesiveness) and general safety (number of subjects with emergent adverse events or changes from baseline to end of study in vital signs, electrocardiogram and clinical laboratory parameters). | up to Day 22 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensory profile | Visual Analogic Scales (sensations linked to patch application and removal) | Day 22 |
| Global assessment by the patient | Visual Analog Scale Scale and questionnaires | Day 22 |
| Subject behaviours | nicotine consumption | up to Day 22 |
|
Smoking cessation, Nicotine, Tobacco Use Disorder, Central Nervous System Agents
|
Cholinergic Agents, Nicotine, Ganglionic Stimulants, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Nicotinic Agonists, Cholinergic Agonists, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V0116<br>One patch per day (during 24 hours) for 21 days | Drug: V0116 transdermal patch<br>* One patch per day (during 24 hours) for 21 days<br>|
| Active Comparator: Reference<br>One patch per day (during 24 hours) for 21 days | Drug: Nicotine transdermal patch<br>* One patch per day (during 24 hours) for 21 days<br>|
|
Nicotine Patch Safety Study
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety profile of a repeated application of a new transdermal patch compared to a reference product during 3 weeks, in a large population.
Conditions
-----------------
Smokers
Intervention / Treatment
-----------------
* Drug: V0116 transdermal patch
* Drug: Nicotine transdermal patch
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female aged more than 18 years Regular smoker motivated to stop tobacco consumption Current smoker of > or = 20 cigarettes/day and < or = 25 cigarettes/day or Fagerström score > or = 5 (for smokers between 10 to 20 cigarettes/day) Exclusion Criteria: Any visible skin disorder, abnormal skin pigmentation or other dermatologic disease which, in the opinion of the investigator would interfere with the assessment of the different parameters Current or past serious chronic cardiovascular, renal, hepatic, gastrointestinal (including duodenal or gastric ulcer), endocrine, hematological, neuropsychiatric, immunosuppressive condition or allergic disease, myopathies, epileptic seizures, bleeding tendency, cancer History of angina pectoris, myocardial infarction or stroke in the previous 3 months, coronary artery vasospasm, cardiac arrhythmia, acute stroke Clinically relevant abnormal findings on the physical examination (e.g large scars on the application zone)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V0116<br>One patch per day (during 24 hours) for 21 days | Drug: V0116 transdermal patch<br>* One patch per day (during 24 hours) for 21 days<br>|
| Active Comparator: Reference<br>One patch per day (during 24 hours) for 21 days | Drug: Nicotine transdermal patch<br>* One patch per day (during 24 hours) for 21 days<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Evaluation of local safety (number of subjects with skin irritation / number of subjects by score of adhesiveness) and general safety (number of subjects with emergent adverse events or changes from baseline to end of study in vital signs, electrocardiogram and clinical laboratory parameters). | up to Day 22 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensory profile | Visual Analogic Scales (sensations linked to patch application and removal) | Day 22 |
| Global assessment by the patient | Visual Analog Scale Scale and questionnaires | Day 22 |
| Subject behaviours | nicotine consumption | up to Day 22 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Smoking cessation, Nicotine, Tobacco Use Disorder, Central Nervous System Agents
|
|
NCT01534273
|
A Study of LY2886721 in Healthy Participants
|
The purpose of this phase I study in healthy participants will be to evaluate the safety and tolerability of LY2886721 single and multiple doses, to evaluate how the body handles the drug, and to evaluate the drug's effect on the body.
|
Single- and Multiple-Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY2886721 in Healthy Subjects
|
Healthy Volunteers
|
* Drug: LY2886721
* Drug: Placebo
|
Inclusion Criteria:~Healthy men and non-childbearing potential women~Body mass index (BMI) between 18.0 and 32.0 kilograms per square meter (kg/m^2)~Are reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures and research unit policies~Exclusion Criteria:~Taking over-the-counter or prescription medication with the exception of vitamins or minerals~Smoke more than 10 cigarettes per day~Drink more than 5 cups of caffeine containing beverages (for example, coffee, tea) per day
|
20 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Significant Effects | Data presented are the number of participants who experienced treatment-emergent adverse events. A summary of serious adverse events and other non-serious adverse events, regardless of causality is reported in the Adverse Events module. | Predose up to Day 23 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Plasma Maximum Observed Concentration (Cmax) of LY2886721 | | Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose |
| Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of LY2886721 | | Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose |
| Pharmacokinetics: Plasma Maximum Observed Concentration at Steady State (Cmax,ss) of LY2886721 | | Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose |
| Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 | AUC over the dosing interval at steady state (AUCtau,ss) is reported for participants who received multiple doses of LY2886721. | Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose |
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at Day 15 | Least squares (LS) mean percent changes from baseline to Day 15 in CSF amyloid 1-40 concentrations for participants in Cohort B are reported. LS means were calculated from an analysis of covariance (ANCOVA) with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% confidence interval (CI) of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline. | Baseline, Day 15 |
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose | LS mean percent changes from baseline to 24 hours post-dose in CSF amyloid 1-40 concentrations for participants in Cohort C are reported. LS means were calculated from an ANCOVA with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% CI of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline. | Baseline, 24 hours post-dose |
|
Mild Cognitive Impairment
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Single oral dose and/or once daily (QD) oral dosing for 14 consecutive days | Drug: Placebo<br>* Administered orally.<br>|
| Experimental: 35 mg LY2886721<br>QD oral dosing for 14 consecutive days | Drug: LY2886721<br>* Administered orally.<br>|
| Experimental: 70 mg LY2886721<br>Single oral dose or single oral dose followed by QD oral dosing for 14 consecutive days | Drug: LY2886721<br>* Administered orally.<br>|
| Experimental: 140 mg LY2886721<br>Single oral dose | Drug: LY2886721<br>* Administered orally.<br>|
|
A Study of LY2886721 in Healthy Participants
Study Overview
=================
Brief Summary
-----------------
The purpose of this phase I study in healthy participants will be to evaluate the safety and tolerability of LY2886721 single and multiple doses, to evaluate how the body handles the drug, and to evaluate the drug's effect on the body.
Official Title
-----------------
Single- and Multiple-Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY2886721 in Healthy Subjects
Conditions
-----------------
Healthy Volunteers
Intervention / Treatment
-----------------
* Drug: LY2886721
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy men and non-childbearing potential women Body mass index (BMI) between 18.0 and 32.0 kilograms per square meter (kg/m^2) Are reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures and research unit policies Exclusion Criteria: Taking over-the-counter or prescription medication with the exception of vitamins or minerals Smoke more than 10 cigarettes per day Drink more than 5 cups of caffeine containing beverages (for example, coffee, tea) per day
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Single oral dose and/or once daily (QD) oral dosing for 14 consecutive days | Drug: Placebo<br>* Administered orally.<br>|
| Experimental: 35 mg LY2886721<br>QD oral dosing for 14 consecutive days | Drug: LY2886721<br>* Administered orally.<br>|
| Experimental: 70 mg LY2886721<br>Single oral dose or single oral dose followed by QD oral dosing for 14 consecutive days | Drug: LY2886721<br>* Administered orally.<br>|
| Experimental: 140 mg LY2886721<br>Single oral dose | Drug: LY2886721<br>* Administered orally.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Significant Effects | Data presented are the number of participants who experienced treatment-emergent adverse events. A summary of serious adverse events and other non-serious adverse events, regardless of causality is reported in the Adverse Events module. | Predose up to Day 23 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Plasma Maximum Observed Concentration (Cmax) of LY2886721 | | Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose |
| Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of LY2886721 | | Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose |
| Pharmacokinetics: Plasma Maximum Observed Concentration at Steady State (Cmax,ss) of LY2886721 | | Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose |
| Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 | AUC over the dosing interval at steady state (AUCtau,ss) is reported for participants who received multiple doses of LY2886721. | Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose |
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at Day 15 | Least squares (LS) mean percent changes from baseline to Day 15 in CSF amyloid 1-40 concentrations for participants in Cohort B are reported. LS means were calculated from an analysis of covariance (ANCOVA) with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% confidence interval (CI) of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline. | Baseline, Day 15 |
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose | LS mean percent changes from baseline to 24 hours post-dose in CSF amyloid 1-40 concentrations for participants in Cohort C are reported. LS means were calculated from an ANCOVA with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% CI of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline. | Baseline, 24 hours post-dose |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mild Cognitive Impairment
|
||
NCT01717768
|
Oral Testosterone for the Treatment of Hypogonadism
|
Low testosterone is a condition that occurs when the body is unable to produce sufficient quantities of testosterone. The medical name for low testosterone is hypogonadism. Hypogonadism can be caused by many factors. Symptoms include: decrease in libido, lack of energy and mood swings. The goal of testosterone replacement therapy is to return testosterone levels to the normal range and relieve symptoms.~The purpose of this study is to evaluate the ability of TSX-002, which is testosterone provided in easy to swallow capsules, to maintain serum (blood) testosterone levels within the normal range in hypogonadal men. This will be determined by blood sampling at specified times during the study. The study is also intended to evaluate the tolerability of TSX-002, which will be taken orally twice per day for 15 days. In addition, the study is intended to determine a dosing regimen(s) that achieves testosterone levels within the normal range. Related Outcome Measures will be reported for Parts 1, 2, and 4.~A portion of the study (Part 3) to also assess the effect of a high-calorie, high-fat meal on the single dose pharmacokinetic exposure of TSX-002. Related outcome measures to be reported for Part 3.
|
A Phase 2, Randomized, Double-blind, Dose Response Study of Oral Testosterone in Subjects With Hypogonadism
|
Hypogonadism
|
* Drug: TSX-002
|
Inclusion Criteria:~Prior documentation of a diagnosis of hypogonadism as evidenced by a screening serum testosterone < 300 ng/dL (based on the average of 2 morning samples taken at least 1 week apart)~Men over the age of 18 years with a body mass index (BMI) < 39.0 kg/m2 and weighing ≥ 55 kg~Hemoglobin levels at screening and baseline > 12.5 g/dL~Testosterone treatment not contraindicated~No evidence of suspected reversible hypogonadism~Willing to abstain from current treatment for hypogonadism in accordance with approved labeling to facilitate an appropriate washout period before study participation (for nondepot formulations of testosterone only)~Understands the requirements of the study and voluntarily consents to participate in the study~Exclusion Criteria:~-
|
18 Years
| null |
Male
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving a 24 Hour Average Total Serum Testosterone Concentration (Cavg,0-24h) in the Range of 300 to 1050 ng/dL After 15 Days of Treatment With TSX-002 | Percentage of subjects achieving a 24-hour average total serum testosterone concentration (Cavg,0-24h) in the range of 300 to 1050 ng/dL after 15 days of treatment with TSX-002. PK samples taken at 0 ,2 ,4, 5 ,6, 7, 9, 12, 14, 16, 17, 18, 21, 24 hours post-dose after 15 days of treatment for Part 1. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 16, 17, 18, 19, 20, 21, 22, 24 hours post-dose after 15 days of treatment for Part 2. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8 ,12, 13, 14, 15, 16, 17, 18, 20, 24 hours post-dose after 15 days of treatment for Part 4. | 15 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Cmax ≤ 1500 ng/dL After 15 Days of Treatment 2. Percentage of Subjects With Cmax ≥ 1800 and ≤ 2500 ng/dL After 15 Days of BID Treatment 3. Percentage of Subjects With Cmax > 2500 ng/dL After 15 Days of BID Treatment | Cmax. PK samples taken at 0, 2, 4, 5, 6, 7, 9, 12, 14, 16, 17, 18, 21, 24 hours post-dose after 15 days of treatment for Part 1. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 16, 17, 18, 19, 20, 21, 22, 24 hours post-dose after 15 days of treatment for Part 2. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 13, 14, 15, 16, 17,18, 20, 24 hours post-dose after 15 days of treatment for Part 4. | 15 days |
|
hypogonadism, Gonadal Disorders, Endocrine System Diseases, Testosterone, Testosterone enanthate, Testosterone undecanoate, Testosterone 17 beta-cypionate, Methyltestosterone, Androgens, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Pharmacologic Actions, Therapeutic Uses, Anabolic Agents
|
Hormones, Testosterone, Androgens, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: 120 mg BID<br>Oral TSX-002 120 mg BID (total dose = 240 mg/day) for a duration of 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 1: 240 mg BID<br>Oral TSX-002 240 mg BID (total dose = 480 mg/day) for a duration of 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 2: 120 mg BID<br>Single cohort, open-label, nonrandomized oral TSX 002 120 mg BID (total dose = 240 mg/day) for a duration of 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 3: A-B-C 120 mg QD<br>Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C.~Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.~Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.~Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 3: B-C-A 120 mg QD<br>Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C.~Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.~Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.~Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 3: C-A-B 120 mg QD<br>Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C.~Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.~Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing.~Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 1: 60 mg BID/ 60 mg TID<br>Oral TSX-002 60 mg BID for 15 days then 60 mg TID for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 2: 90 mg BID/ 90 mg TID<br>Oral TSX-002 90 mg BID for 15 days then 90 mg TID for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 3: 180 mg QD<br>Oral TSX-002 180 mg once daily (QD) for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 4: 120 mg BID<br>Oral TSX-002 120 mg BID for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
|
Oral Testosterone for the Treatment of Hypogonadism
Study Overview
=================
Brief Summary
-----------------
Low testosterone is a condition that occurs when the body is unable to produce sufficient quantities of testosterone. The medical name for low testosterone is hypogonadism. Hypogonadism can be caused by many factors. Symptoms include: decrease in libido, lack of energy and mood swings. The goal of testosterone replacement therapy is to return testosterone levels to the normal range and relieve symptoms. The purpose of this study is to evaluate the ability of TSX-002, which is testosterone provided in easy to swallow capsules, to maintain serum (blood) testosterone levels within the normal range in hypogonadal men. This will be determined by blood sampling at specified times during the study. The study is also intended to evaluate the tolerability of TSX-002, which will be taken orally twice per day for 15 days. In addition, the study is intended to determine a dosing regimen(s) that achieves testosterone levels within the normal range. Related Outcome Measures will be reported for Parts 1, 2, and 4. A portion of the study (Part 3) to also assess the effect of a high-calorie, high-fat meal on the single dose pharmacokinetic exposure of TSX-002. Related outcome measures to be reported for Part 3.
Official Title
-----------------
A Phase 2, Randomized, Double-blind, Dose Response Study of Oral Testosterone in Subjects With Hypogonadism
Conditions
-----------------
Hypogonadism
Intervention / Treatment
-----------------
* Drug: TSX-002
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Prior documentation of a diagnosis of hypogonadism as evidenced by a screening serum testosterone < 300 ng/dL (based on the average of 2 morning samples taken at least 1 week apart) Men over the age of 18 years with a body mass index (BMI) < 39.0 kg/m2 and weighing ≥ 55 kg Hemoglobin levels at screening and baseline > 12.5 g/dL Testosterone treatment not contraindicated No evidence of suspected reversible hypogonadism Willing to abstain from current treatment for hypogonadism in accordance with approved labeling to facilitate an appropriate washout period before study participation (for nondepot formulations of testosterone only) Understands the requirements of the study and voluntarily consents to participate in the study Exclusion Criteria: -
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: 120 mg BID<br>Oral TSX-002 120 mg BID (total dose = 240 mg/day) for a duration of 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 1: 240 mg BID<br>Oral TSX-002 240 mg BID (total dose = 480 mg/day) for a duration of 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 2: 120 mg BID<br>Single cohort, open-label, nonrandomized oral TSX 002 120 mg BID (total dose = 240 mg/day) for a duration of 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 3: A-B-C 120 mg QD<br>Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C. Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 3: B-C-A 120 mg QD<br>Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C. Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 3: C-A-B 120 mg QD<br>Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C. Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 1: 60 mg BID/ 60 mg TID<br>Oral TSX-002 60 mg BID for 15 days then 60 mg TID for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 2: 90 mg BID/ 90 mg TID<br>Oral TSX-002 90 mg BID for 15 days then 90 mg TID for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 3: 180 mg QD<br>Oral TSX-002 180 mg once daily (QD) for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 4: 120 mg BID<br>Oral TSX-002 120 mg BID for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving a 24 Hour Average Total Serum Testosterone Concentration (Cavg,0-24h) in the Range of 300 to 1050 ng/dL After 15 Days of Treatment With TSX-002 | Percentage of subjects achieving a 24-hour average total serum testosterone concentration (Cavg,0-24h) in the range of 300 to 1050 ng/dL after 15 days of treatment with TSX-002. PK samples taken at 0 ,2 ,4, 5 ,6, 7, 9, 12, 14, 16, 17, 18, 21, 24 hours post-dose after 15 days of treatment for Part 1. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 16, 17, 18, 19, 20, 21, 22, 24 hours post-dose after 15 days of treatment for Part 2. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8 ,12, 13, 14, 15, 16, 17, 18, 20, 24 hours post-dose after 15 days of treatment for Part 4. | 15 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Cmax ≤ 1500 ng/dL After 15 Days of Treatment 2. Percentage of Subjects With Cmax ≥ 1800 and ≤ 2500 ng/dL After 15 Days of BID Treatment 3. Percentage of Subjects With Cmax > 2500 ng/dL After 15 Days of BID Treatment | Cmax. PK samples taken at 0, 2, 4, 5, 6, 7, 9, 12, 14, 16, 17, 18, 21, 24 hours post-dose after 15 days of treatment for Part 1. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 16, 17, 18, 19, 20, 21, 22, 24 hours post-dose after 15 days of treatment for Part 2. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 13, 14, 15, 16, 17,18, 20, 24 hours post-dose after 15 days of treatment for Part 4. | 15 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hypogonadism, Gonadal Disorders, Endocrine System Diseases, Testosterone, Testosterone enanthate, Testosterone undecanoate, Testosterone 17 beta-cypionate, Methyltestosterone, Androgens, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs, Pharmacologic Actions, Therapeutic Uses, Anabolic Agents
|
|
NCT01473745
|
The Nasal Changes Affected by Different Alar Base Suture Techniques After Maxillary LeFort I Osteotomy
|
study hypothesis~The aim of this study:~How can the investigators predict and control the nasal changes after maxillary LeFort I osteotomy with 2 different alar base suture techniques ?~Study hypothesis~Null hypothesis: Nasal changes were not affected by 2 different alar base suture techniques after maxillary LeFort I osteotomy~Alternative : Nasal changes were affected by 2 different alar base suture techniques after maxillary LeFort I osteotomy
|
Background and study purpose:~Patients who received maxillary LeFort I osteotomy often complained about their nose become wider and more nostril show after surgery. According the the literature review, the conventional and modified alar base cinch technique both could control the interalar width. However, there is no long term result show which technique is superior to the other. Therefore, in order to improve patients' nasal and midfacial esthetics after the surgery, this study is to evaluate how the nasal changes affected by 2 different alar base cinch suture and which technique could result in a more positive effect.
|
The Nasal Changes Affected by 2 Different Alar Base Suture Techniques After Maxillary LeFort I Osteotomy--A Randomized Controlled Trial
|
Conditions in T74.31 or T76.31
|
* Procedure: conventional alar base cinch
* Procedure: modified alar base cinch
|
Inclusion Criteria:~Taiwanese patients who received LeFort I osteotomy at CGMH during 2011-2012~No previous craniofacial surgery~Patients agreed to attend this study and willing to sign the agreement~Patients who are elder than 18 years old and after growth completion~Exclusion Criteria:~Craniofacial anomalies~cleft lip and /or palate patients~patients without all the documents~patients do not receive combined correcting nasolabial shape and orthognathic surgery.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Soft and Hard Tissue Landmarks Movement | The investigator measured the movement (1 month minus baseline) of hard tissue landmarks before and after 4-6 weeks maxillary LeFort I osteotomy. The movement (6 months minus baseline) of soft tissue landmarks was measured before and after 6 months of the maxillary LeFort I osteotomy.~The 3D directional movement of each point was measured in the x(transverse), y(vertical), and z (antero-posterior)planes. The positive directional movement of each point in X axis means the point moved left after surgery, and negative directional movement in X axis means the the point moved right after surgery. The positive directional movement in Y axis means the point moved upward after surgery, and negative directional movement in Y axis means the the point moved downward after surgery. The positive directional movement in Z axis means the point moved anteriorly after surgery, and negative directional movement in Z axis means the the point moved posteriorly after surgery. | The hard tissue movements were assessed after surgery 4-6 weeks.The soft tissue movements were assessed after surgery 6 months. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 14 Nasolabial Linear Parameters | baseline characteristics: intercanthulus distance~nasal linear parameters~nasolabial linear parameters | up to post-operation 6 months |
| 1 Nasolabial Angular Parameters | 2D nasolabial angular parameter: Nasolabial angle (NLA) (The NLA was a two dimensional measurement and was measured at the midsagittal plane with Image J software®) | up to post-operation 6 months |
|
Alar Base Suture; Nasolabial Change; 3D stereogrammetry
|
Daminozide, Plant Growth Regulators, Growth Substances, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: modified alar base cinch suture<br>Before closure of the maxillary wound, an alar base cinch suture was performed with 3-O Nylon. The modified alar cinch suture began from the bilateral alar part of the nasalis muscle and dermis tissue over the alar base, and then passed through a hole drilled on the anterior nasal spine. | Procedure: modified alar base cinch<br>* The modified suture began from the bilateral alar part of the nasalis muscle and dermis tissue over the alar base, and then passed through a hole drilled on the anterior nasal spine.<br>* Other names: modified alar base cinch technique;|
| Placebo Comparator: conventional alar base cinch suture<br>Before closure of the maxillary wound, an alar base cinch suture was performed with 3-O Nylon. The conventional alar base cinch suture began from the bilateral alar part of the nasalis muscle and passed through a hole drilled on the anterior nasal spine. | Procedure: conventional alar base cinch<br>* The conventional suture began from the bilateral alar part of the nasalis muscle and passed through a hole drilled on the anterior nasal spine.<br>* Other names: conventional alar cinch suture technique;|
|
The Nasal Changes Affected by Different Alar Base Suture Techniques After Maxillary LeFort I Osteotomy
Study Overview
=================
Brief Summary
-----------------
study hypothesis The aim of this study: How can the investigators predict and control the nasal changes after maxillary LeFort I osteotomy with 2 different alar base suture techniques ? Study hypothesis Null hypothesis: Nasal changes were not affected by 2 different alar base suture techniques after maxillary LeFort I osteotomy Alternative : Nasal changes were affected by 2 different alar base suture techniques after maxillary LeFort I osteotomy
Detailed Description
-----------------
Background and study purpose: Patients who received maxillary LeFort I osteotomy often complained about their nose become wider and more nostril show after surgery. According the the literature review, the conventional and modified alar base cinch technique both could control the interalar width. However, there is no long term result show which technique is superior to the other. Therefore, in order to improve patients' nasal and midfacial esthetics after the surgery, this study is to evaluate how the nasal changes affected by 2 different alar base cinch suture and which technique could result in a more positive effect.
Official Title
-----------------
The Nasal Changes Affected by 2 Different Alar Base Suture Techniques After Maxillary LeFort I Osteotomy--A Randomized Controlled Trial
Conditions
-----------------
Conditions in T74.31 or T76.31
Intervention / Treatment
-----------------
* Procedure: conventional alar base cinch
* Procedure: modified alar base cinch
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Taiwanese patients who received LeFort I osteotomy at CGMH during 2011-2012 No previous craniofacial surgery Patients agreed to attend this study and willing to sign the agreement Patients who are elder than 18 years old and after growth completion Exclusion Criteria: Craniofacial anomalies cleft lip and /or palate patients patients without all the documents patients do not receive combined correcting nasolabial shape and orthognathic surgery.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: modified alar base cinch suture<br>Before closure of the maxillary wound, an alar base cinch suture was performed with 3-O Nylon. The modified alar cinch suture began from the bilateral alar part of the nasalis muscle and dermis tissue over the alar base, and then passed through a hole drilled on the anterior nasal spine. | Procedure: modified alar base cinch<br>* The modified suture began from the bilateral alar part of the nasalis muscle and dermis tissue over the alar base, and then passed through a hole drilled on the anterior nasal spine.<br>* Other names: modified alar base cinch technique;|
| Placebo Comparator: conventional alar base cinch suture<br>Before closure of the maxillary wound, an alar base cinch suture was performed with 3-O Nylon. The conventional alar base cinch suture began from the bilateral alar part of the nasalis muscle and passed through a hole drilled on the anterior nasal spine. | Procedure: conventional alar base cinch<br>* The conventional suture began from the bilateral alar part of the nasalis muscle and passed through a hole drilled on the anterior nasal spine.<br>* Other names: conventional alar cinch suture technique;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Soft and Hard Tissue Landmarks Movement | The investigator measured the movement (1 month minus baseline) of hard tissue landmarks before and after 4-6 weeks maxillary LeFort I osteotomy. The movement (6 months minus baseline) of soft tissue landmarks was measured before and after 6 months of the maxillary LeFort I osteotomy. The 3D directional movement of each point was measured in the x(transverse), y(vertical), and z (antero-posterior)planes. The positive directional movement of each point in X axis means the point moved left after surgery, and negative directional movement in X axis means the the point moved right after surgery. The positive directional movement in Y axis means the point moved upward after surgery, and negative directional movement in Y axis means the the point moved downward after surgery. The positive directional movement in Z axis means the point moved anteriorly after surgery, and negative directional movement in Z axis means the the point moved posteriorly after surgery. | The hard tissue movements were assessed after surgery 4-6 weeks.The soft tissue movements were assessed after surgery 6 months. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 14 Nasolabial Linear Parameters | baseline characteristics: intercanthulus distance nasal linear parameters nasolabial linear parameters | up to post-operation 6 months |
| 1 Nasolabial Angular Parameters | 2D nasolabial angular parameter: Nasolabial angle (NLA) (The NLA was a two dimensional measurement and was measured at the midsagittal plane with Image J software®) | up to post-operation 6 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alar Base Suture; Nasolabial Change; 3D stereogrammetry
|
NCT00501059
|
A Study to Assess the Efficacy and Safety of Enteric-Coated Acetylsalicylic Acid in Patients at Moderate Risk of Cardiovascular Disease
|
The use of acetylsalicylic acid in the primary prevention of cardiovascular events has been extensively studied but to a lesser extent in patients with moderate levels of cardiovascular risk. The current study is designed to prove the efficacy and tolerability of 100 mg enteric-coated Aspirin versus placebo in the prevention of cardiovascular disease (CVD) events, which include fatal and nonfatal myocardial infarction, fatal and nonfatal stroke and CV death, in a population with no history of known CVD who are at moderate risk of major CHD events (approximately 10-20% 10 year CHD risk). This corresponds to a patient population mean 10-year CVD risk of approximately 30%. Subjects are treated in a standard care setting and may receive treatment for the underlying risk factors as defined by the treating physician. Outcome events will be adjudicated by an Endpoint Adjudication Committee and the study will be monitored by an independent Data Safety Monitoring Board.
|
Summary of substantial Protocol amendments~Amendment #2 from 09-APR-2008:~Systolic blood pressure (SBP) limit of 170 mmHg has been added to the exclusion criteria~Exclusion of patients currently taking anticoagulant medication~A longer interval between the daily dose of study drug and ibuprofen~Revised wording in moderate risk definitions for coronary heart disease (CHD) and cerebrovascular disease (CVD): To evaluate the clinical effects of a 100 mg/day enteric-coated acetylsalicylic acid versus placebo in the reduction of CVD events in patients at moderate risk of major CHD events (approximately 10 to 20% 10-year CHD risk; approximately 20 to 30% 10-year risk of CVD). This corresponds to a patient population mean 10-year CVD risk of approximately 30%.~Amendment #3 from 02-JAN-2009~• Increase in the number of allowed risk factors for males, age is no longer a risk factor~Amendment #4 from 02-OCT-2013~The primary endpoint is changed to include confirmed UA and TIA.~The estimated event rate is changed to 1.5% per year due to new information.~Effect size (risk reduction) changed from 14.9% to 17 to 18%.~Achieving 60,000 person-years instead of 1488 primary endpoint events~Additional treatment and follow-up for a maximum of another 12 months.~Change to reduced adverse event and concomitant therapy reporting
|
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel Group Study to Assess the Efficacy (Reduction of Cardiovascular Disease Events) and Safety of 100 mg Enteric-Coated Acetylsalicylic Acid in Patients at Moderate Risk of Cardiovascular Disease
|
Moderate Risk of CVD
|
* Drug: Aspirin (Acetylsalicylic acid, BAYE4465)
* Drug: Placebo
|
Inclusion Criteria:~Males aged 55 years and above with 2 to 4 risk factors. Male Risk Factors:~Elevated cholesterol (Tchol>200 mg/dL or LDL>130 mg/dL; as measured at screening) irrespective of current treatment~Current smoking: defined as any cigarette smoking in the past 12 months~Low HDL cholesterol (HDL<40 mg/dL; as measured at screening)~Elevated blood pressure (SBP>140 mmHg; as measured at screening)~Currently on any medication to treat high blood pressure~Positive family history of early CHD (a first-degree relative [father, mother, brother, sister, son, daughter] suffered a heart attack [myocardial infarction] before the age of 60 years)~Females aged 60 and above with 3 or more risk factors. Female Risk Factors:~Elevated cholesterol (Tchol>240 mg/dL or LDL>160 mg/dL; as measured at screening) irrespective of current treatment~Current smoking: defined as any cigarette smoking in the past 12 months~Low HDL cholesterol (HDL<40 mg/dL; as measured at screening)~Elevated blood pressure (SBP>140 mmHg; as measured at screening)~Currently on any medication to treat high blood pressure~Positive family history of early CHD (a first-degree relative [father, mother, brother, sister, son, daughter] suffered a heart attack [myocardial infarction] before the age of 60 years)~An understanding and willingness to comply with trial procedures and has given written informed consent to participate in the trial~Exclusion Criteria:~History of a documented vascular event, such as MI, stroke, coronary artery angioplasty or stenting, coronary artery bypass graft, relevant arrhythmias, or congestive heart failure or vascular intervention~Patients who are at higher than moderate risk on the basis of their diabetes status, other factors known to the investigator, or the currently used national risk score~Known contraindications to the study drug, e.g. hypersensitivity to acetylsalicylic acid~Recent (in the past year) history of gastrointestinal or genitourinary bleeding or other bleeding disorders~Active diagnosed and documented reflux esophagitis~Patients presenting with any medical condition, or psychiatric or substance abuse disorder, that, in the opinion of the investigator, is likely to affect the patient's ability to complete the study or precludes the patient's participation in the study~Lactating women or women of childbearing potential~Severe liver disease or damage based on the clinical judgment of the investigator~Severe renal disease or damage based on the clinical judgement of the investigator~A definite indication for acetylsalicylic acid therapy, other antiplatelet drug, or anticoagulant in the opinion of the physician~A history of asthma induced by administration of salicylates or substances with a similar action, notably NSAIDS~Chronic, frequent (> 5 days/month) use of NSAIDs (including aspirin, or aspirin containing products), COX-2 inhibitors or metamizole~Current participation in any other trials involving investigational products within 30 days prior to the Screening Visit~Current use of an anticoagulant medication~Sitting systolic blood pressure greater than 170 mmHg
|
55 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First Occurrence of the Composite Outcome of MI (Myocardial Infarction), Stroke, Cardiovascular Death, UA (Unstable Angina) or TIA (Transient Ischemic Attack) | The primary efficacy endpoint was a composite outcome consisting of the first occurrence of confirmed MI, stroke, cardiovascular death, UA, TIA. The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses. | Until follow-up (approximate 6 years) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First Occurrence of the Composite Outcome of Cardiovascular Death, MI, or Stroke (Ischemic, Hemorrhagic, or Unknown) | The time to Composite outcome consisting of the first occurrence of cardiovascular death, MI, or stroke (ischemic, hemorrhagic, or unknown) was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses. | Until follow-up (approximate 6 years) |
| Time to the First Occurrence of the Individual Components of the Primary: Non-fatal MI, Total MI, Non-fatal Stroke, Total Stroke, Cardiovascular Death, UA and TIA | The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses. | Until follow-up (approximately 6 years) |
| Time to All-cause Mortality, the First Occurrence of All Cancers Excluding Non-melanoma Skin Cancer (NMSC) and the First Occurrence of Colon Cancer | The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses. | Until follow-up (approximately 6 years) |
| Incidence of All-cause Mortality, All Cancers Excluding Non-melanoma Skin Cancer and Colon Cancer | | Until follow-up (approximately 6 years) |
| Incidence of Confirmed MI, Stroke, Cardiovascular Death, UA, and TIA Separately | The percentages of subjects with the efficacy endpoints of confirmed MI, stroke, cardiovascular death, UA and TIA are reported separately. *all other CV death without fatal MI and fatal stroke | Until follow-up (approximately 6 years) |
|
Primary prevention of coronary heart disease, Stroke and cardiovascular death, Aspirin
|
Aspirin, Antirheumatic Agents, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Inflammatory Agents, Fibrinolytic Agents, Fibrin Modulating Agents, Molecular Mechanisms of Pharmacological Action, Platelet Aggregation Inhibitors, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Antipyretics
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetylsalicylic acid (Aspirin, BAYE4465)<br>Participants received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily. | Drug: Aspirin (Acetylsalicylic acid, BAYE4465)<br>* 100mg enteric coated Aspirin, taken daily<br>|
| Placebo Comparator: Placebo<br>Participants received 1 tablets of matching placebo orally once daily. | Drug: Placebo<br>* Placebo, taken daily<br>|
|
A Study to Assess the Efficacy and Safety of Enteric-Coated Acetylsalicylic Acid in Patients at Moderate Risk of Cardiovascular Disease
Study Overview
=================
Brief Summary
-----------------
The use of acetylsalicylic acid in the primary prevention of cardiovascular events has been extensively studied but to a lesser extent in patients with moderate levels of cardiovascular risk. The current study is designed to prove the efficacy and tolerability of 100 mg enteric-coated Aspirin versus placebo in the prevention of cardiovascular disease (CVD) events, which include fatal and nonfatal myocardial infarction, fatal and nonfatal stroke and CV death, in a population with no history of known CVD who are at moderate risk of major CHD events (approximately 10-20% 10 year CHD risk). This corresponds to a patient population mean 10-year CVD risk of approximately 30%. Subjects are treated in a standard care setting and may receive treatment for the underlying risk factors as defined by the treating physician. Outcome events will be adjudicated by an Endpoint Adjudication Committee and the study will be monitored by an independent Data Safety Monitoring Board.
Detailed Description
-----------------
Summary of substantial Protocol amendments Amendment #2 from 09-APR-2008: Systolic blood pressure (SBP) limit of 170 mmHg has been added to the exclusion criteria Exclusion of patients currently taking anticoagulant medication A longer interval between the daily dose of study drug and ibuprofen Revised wording in moderate risk definitions for coronary heart disease (CHD) and cerebrovascular disease (CVD): To evaluate the clinical effects of a 100 mg/day enteric-coated acetylsalicylic acid versus placebo in the reduction of CVD events in patients at moderate risk of major CHD events (approximately 10 to 20% 10-year CHD risk; approximately 20 to 30% 10-year risk of CVD). This corresponds to a patient population mean 10-year CVD risk of approximately 30%. Amendment #3 from 02-JAN-2009 • Increase in the number of allowed risk factors for males, age is no longer a risk factor Amendment #4 from 02-OCT-2013 The primary endpoint is changed to include confirmed UA and TIA. The estimated event rate is changed to 1.5% per year due to new information. Effect size (risk reduction) changed from 14.9% to 17 to 18%. Achieving 60,000 person-years instead of 1488 primary endpoint events Additional treatment and follow-up for a maximum of another 12 months. Change to reduced adverse event and concomitant therapy reporting
Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel Group Study to Assess the Efficacy (Reduction of Cardiovascular Disease Events) and Safety of 100 mg Enteric-Coated Acetylsalicylic Acid in Patients at Moderate Risk of Cardiovascular Disease
Conditions
-----------------
Moderate Risk of CVD
Intervention / Treatment
-----------------
* Drug: Aspirin (Acetylsalicylic acid, BAYE4465)
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males aged 55 years and above with 2 to 4 risk factors. Male Risk Factors: Elevated cholesterol (Tchol>200 mg/dL or LDL>130 mg/dL; as measured at screening) irrespective of current treatment Current smoking: defined as any cigarette smoking in the past 12 months Low HDL cholesterol (HDL<40 mg/dL; as measured at screening) Elevated blood pressure (SBP>140 mmHg; as measured at screening) Currently on any medication to treat high blood pressure Positive family history of early CHD (a first-degree relative [father, mother, brother, sister, son, daughter] suffered a heart attack [myocardial infarction] before the age of 60 years) Females aged 60 and above with 3 or more risk factors. Female Risk Factors: Elevated cholesterol (Tchol>240 mg/dL or LDL>160 mg/dL; as measured at screening) irrespective of current treatment Current smoking: defined as any cigarette smoking in the past 12 months Low HDL cholesterol (HDL<40 mg/dL; as measured at screening) Elevated blood pressure (SBP>140 mmHg; as measured at screening) Currently on any medication to treat high blood pressure Positive family history of early CHD (a first-degree relative [father, mother, brother, sister, son, daughter] suffered a heart attack [myocardial infarction] before the age of 60 years) An understanding and willingness to comply with trial procedures and has given written informed consent to participate in the trial Exclusion Criteria: History of a documented vascular event, such as MI, stroke, coronary artery angioplasty or stenting, coronary artery bypass graft, relevant arrhythmias, or congestive heart failure or vascular intervention Patients who are at higher than moderate risk on the basis of their diabetes status, other factors known to the investigator, or the currently used national risk score Known contraindications to the study drug, e.g. hypersensitivity to acetylsalicylic acid Recent (in the past year) history of gastrointestinal or genitourinary bleeding or other bleeding disorders Active diagnosed and documented reflux esophagitis Patients presenting with any medical condition, or psychiatric or substance abuse disorder, that, in the opinion of the investigator, is likely to affect the patient's ability to complete the study or precludes the patient's participation in the study Lactating women or women of childbearing potential Severe liver disease or damage based on the clinical judgment of the investigator Severe renal disease or damage based on the clinical judgement of the investigator A definite indication for acetylsalicylic acid therapy, other antiplatelet drug, or anticoagulant in the opinion of the physician A history of asthma induced by administration of salicylates or substances with a similar action, notably NSAIDS Chronic, frequent (> 5 days/month) use of NSAIDs (including aspirin, or aspirin containing products), COX-2 inhibitors or metamizole Current participation in any other trials involving investigational products within 30 days prior to the Screening Visit Current use of an anticoagulant medication Sitting systolic blood pressure greater than 170 mmHg
Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetylsalicylic acid (Aspirin, BAYE4465)<br>Participants received 1 tablet of enteric-coated acetylsalicylic acid [100 milligram (mg)] orally once daily. | Drug: Aspirin (Acetylsalicylic acid, BAYE4465)<br>* 100mg enteric coated Aspirin, taken daily<br>|
| Placebo Comparator: Placebo<br>Participants received 1 tablets of matching placebo orally once daily. | Drug: Placebo<br>* Placebo, taken daily<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First Occurrence of the Composite Outcome of MI (Myocardial Infarction), Stroke, Cardiovascular Death, UA (Unstable Angina) or TIA (Transient Ischemic Attack) | The primary efficacy endpoint was a composite outcome consisting of the first occurrence of confirmed MI, stroke, cardiovascular death, UA, TIA. The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses. | Until follow-up (approximate 6 years) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First Occurrence of the Composite Outcome of Cardiovascular Death, MI, or Stroke (Ischemic, Hemorrhagic, or Unknown) | The time to Composite outcome consisting of the first occurrence of cardiovascular death, MI, or stroke (ischemic, hemorrhagic, or unknown) was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses. | Until follow-up (approximate 6 years) |
| Time to the First Occurrence of the Individual Components of the Primary: Non-fatal MI, Total MI, Non-fatal Stroke, Total Stroke, Cardiovascular Death, UA and TIA | The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses. | Until follow-up (approximately 6 years) |
| Time to All-cause Mortality, the First Occurrence of All Cancers Excluding Non-melanoma Skin Cancer (NMSC) and the First Occurrence of Colon Cancer | The time to event was defined as the number of days from the date of randomization to the date of the event confirmed by adjudication. The numbers of days for milestones when 1%, 2%, 3% and 4% of the subjects have reached endpoint events were estimated from Kaplan-Meier-Analyses. | Until follow-up (approximately 6 years) |
| Incidence of All-cause Mortality, All Cancers Excluding Non-melanoma Skin Cancer and Colon Cancer | | Until follow-up (approximately 6 years) |
| Incidence of Confirmed MI, Stroke, Cardiovascular Death, UA, and TIA Separately | The percentages of subjects with the efficacy endpoints of confirmed MI, stroke, cardiovascular death, UA and TIA are reported separately. *all other CV death without fatal MI and fatal stroke | Until follow-up (approximately 6 years) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Primary prevention of coronary heart disease, Stroke and cardiovascular death, Aspirin
|
NCT03597178
|
Contact Lens Insertion and Removal in a Senior Subject Demographic
|
This will be a pilot, one-visit, open-label, non-dispensing study. Subjects will be given instructions and then attempt to insert and remove a contact lens in each eye.
|
Contact Lens Insertion and Removal in a Senior Subject Demographic
|
Visual Acuity
|
* Device: senofilcon A
|
Inclusion Criteria:~Potential subjects must satisfy all of the following criteria to be enrolled in the study:~The subject must read, understand, and sign the STATEMENT OF INFORMED CONSENT and receive a fully executed copy of the form.~Appear able and willing to adhere to the instructions set forth in this clinical protocol.~Must be at least 60 years of age at the time of screening.~The subject must have normal eyes (i.e., no ocular medications or infections of any type).~The subject must have best corrected visual acuity (BCVA) of 20/30 or better in each eye.~Exclusion Criteria:~Potential subjects who meet any of the following criteria will be excluded from participating in the study:~A habitual and adapted wearer of contact lenses (have worn a contact lens at least one time in the past 5 years).~Currently pregnant or lactating (subjects who become pregnant during the study will be discontinued).~Any systemic disease, autoimmune disease, or use of medication that may interfere with contact lens wear.~Any ocular infection.~Any corneal distortion resulting from previous hard or rigid gas permeable contact lens wear.~Participation in any contact lens or lens care product clinical trial within 14 days prior to study enrollment.~History of binocular vision abnormality or strabismus.~Any infectious disease (e.g., hepatitis, tuberculosis) or a contagious immunosuppressive disease (e.g., HIV, by self-report).~Suspicion of or recent history of alcohol or substance abuse.~History of serious mental illness.~History of seizures.~Employee of investigational clinic (e.g., Investigator, Coordinator, Technician)~Any ocular allergies, infections or other ocular abnormalities that are known to interfere with contact lens wear and/or participation in the study. This may include, but not be limited to entropion, ectropion, extrusions, chalazia, recurrent styes, glaucoma, history of recurrent corneal erosions, aphakia, or corneal distortion~Any Grade 3 or greater slit lamp findings (e.g., edema, corneal neovascularization, corneal staining, tarsal abnormalities, conjunctival injection) on the FDA classification scale~Any previous history or signs of a contact lens-related corneal inflammatory event (e.g., past peripheral ulcer or round peripheral scar), or any other ocular abnormality that may contraindicate contact lens wear.
|
60 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Success Rate of Insertion and Removal of a Contact Lens | The subject attempted to insert a contact lens in each eye. The subject were allowed to voluntarily end the contact lens insertion activity at any time prior to the 20-minute time point. The time of insertion for each eye or the time of stopping the insertion process for each eye was recorded. Similarly, the time of removal for each lens or the time of stopping the removal process for each lens was recorded. | Lens insertion and Removal, up to 2-Hours |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: senofilcon A<br>Subjects that are of at least 60 years of age and non-habitual contact lens wearers will receive instructions to insert and remove a contact lens from each eye. | Device: senofilcon A<br>* ACUVUE OASYS® 1-DAY with HydraLuxe™ Technology<br>|
|
Contact Lens Insertion and Removal in a Senior Subject Demographic
Study Overview
=================
Brief Summary
-----------------
This will be a pilot, one-visit, open-label, non-dispensing study. Subjects will be given instructions and then attempt to insert and remove a contact lens in each eye.
Official Title
-----------------
Contact Lens Insertion and Removal in a Senior Subject Demographic
Conditions
-----------------
Visual Acuity
Intervention / Treatment
-----------------
* Device: senofilcon A
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Potential subjects must satisfy all of the following criteria to be enrolled in the study: The subject must read, understand, and sign the STATEMENT OF INFORMED CONSENT and receive a fully executed copy of the form. Appear able and willing to adhere to the instructions set forth in this clinical protocol. Must be at least 60 years of age at the time of screening. The subject must have normal eyes (i.e., no ocular medications or infections of any type). The subject must have best corrected visual acuity (BCVA) of 20/30 or better in each eye. Exclusion Criteria: Potential subjects who meet any of the following criteria will be excluded from participating in the study: A habitual and adapted wearer of contact lenses (have worn a contact lens at least one time in the past 5 years). Currently pregnant or lactating (subjects who become pregnant during the study will be discontinued). Any systemic disease, autoimmune disease, or use of medication that may interfere with contact lens wear. Any ocular infection. Any corneal distortion resulting from previous hard or rigid gas permeable contact lens wear. Participation in any contact lens or lens care product clinical trial within 14 days prior to study enrollment. History of binocular vision abnormality or strabismus. Any infectious disease (e.g., hepatitis, tuberculosis) or a contagious immunosuppressive disease (e.g., HIV, by self-report). Suspicion of or recent history of alcohol or substance abuse. History of serious mental illness. History of seizures. Employee of investigational clinic (e.g., Investigator, Coordinator, Technician) Any ocular allergies, infections or other ocular abnormalities that are known to interfere with contact lens wear and/or participation in the study. This may include, but not be limited to entropion, ectropion, extrusions, chalazia, recurrent styes, glaucoma, history of recurrent corneal erosions, aphakia, or corneal distortion Any Grade 3 or greater slit lamp findings (e.g., edema, corneal neovascularization, corneal staining, tarsal abnormalities, conjunctival injection) on the FDA classification scale Any previous history or signs of a contact lens-related corneal inflammatory event (e.g., past peripheral ulcer or round peripheral scar), or any other ocular abnormality that may contraindicate contact lens wear.
Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: senofilcon A<br>Subjects that are of at least 60 years of age and non-habitual contact lens wearers will receive instructions to insert and remove a contact lens from each eye. | Device: senofilcon A<br>* ACUVUE OASYS® 1-DAY with HydraLuxe™ Technology<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Success Rate of Insertion and Removal of a Contact Lens | The subject attempted to insert a contact lens in each eye. The subject were allowed to voluntarily end the contact lens insertion activity at any time prior to the 20-minute time point. The time of insertion for each eye or the time of stopping the insertion process for each eye was recorded. Similarly, the time of removal for each lens or the time of stopping the removal process for each lens was recorded. | Lens insertion and Removal, up to 2-Hours |
|
||||
NCT03142828
|
Implant Healing Abutment and Chlorhexidine
|
The work hyposesis is based on the application of a chlorhexidine gel against the non-application on the healing abutments in patients who have received a submerged titanium implant to check its effect on healing and prevention of bacterial plaque accumulation during a period of 1 month.
|
Once the implants are integrated, and given the consent, the patients will be operated to connect the healing abutments as they come from the manufacturer (Mozo Grau, Ticare®). Patients will follow the study protocol in 2 arms.~The random distribution is made prior to assignment following the internet program https://www.random.org
|
Effect of the Application of Chlorhexidine in the Pillars of Implant Healing to Prevent Plate Accumulation. Controlled Random Blind Clinical Study.
|
Periimplantitis
|
* Drug: Chlorhexidine
* Other: Placebo
|
Inclusion Criteria:~Good systemic health status (ASA I or II).~No current pain.~No use of painkillers or Anti-inflammatory drugs in the prior weeks.~Older than 18 years.~Oral hygiene index of ≤ 2 (Löe and Silness).~A minimum of 2 mm of adhered gum.~A minimum of 8 mm of vertical bone.~A minimum of 7 mm of vestibule-lingual bone.~Scheduled to receive a unitary implant.~Willing to participate in this controlled study.~Exclusion Criteria:~Pregnant or nursing women.~Use of any type of medication that might affect the perception of pain.~An history of alcohol or drug abuse.~A requirement for guided regeneration or sinus lifting procedures.~Failure to comply with the study protocol.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: After the first week, the healling abutment will be randomly distributed in a test group with application of chlorhexidine gel or a control group without the application of the chlorhexidine gel.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of inflammation | Degree of inflammation was measured using a 4-point Likert scaleInflammation 0 = non-inflamed gingiva with pale pink color. Inflammation 1 = erythematous gingiva without bleeding on manipulation. Inflammation 2 = gingiva with slight bleeding during manipulation during unscrewing or screwing of the abutment. Inflammation 3 = gingiva with heavy bleeding during manipulation during unscrewing or screwing of the abutment. | 1 month after second surgery |
|
chlorhexidine, dental implant, in-situ drug delivery,
|
Chlorhexidine, Anti-Infective Agents, Local, Anti-Infective Agents, Disinfectants
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Test (clorhexidine gel)<br>The healing abutments were covered by a chlorhexidine gel after the first week of the second surgery (2-stage implants). | Drug: Chlorhexidine<br>* Healing abutment with Clorhexidine<br>* Other names: CHX;|
| Placebo Comparator: Placebo<br>The healing abutments were covered without any antiseptic gel after the first week of the second surgery (2-stage implants). | Other: Placebo<br>* Healing abutment without any antiseptic<br>|
|
Implant Healing Abutment and Chlorhexidine
Study Overview
=================
Brief Summary
-----------------
The work hyposesis is based on the application of a chlorhexidine gel against the non-application on the healing abutments in patients who have received a submerged titanium implant to check its effect on healing and prevention of bacterial plaque accumulation during a period of 1 month.
Detailed Description
-----------------
Once the implants are integrated, and given the consent, the patients will be operated to connect the healing abutments as they come from the manufacturer (Mozo Grau, Ticare®). Patients will follow the study protocol in 2 arms. The random distribution is made prior to assignment following the internet program https://www.random.org
Official Title
-----------------
Effect of the Application of Chlorhexidine in the Pillars of Implant Healing to Prevent Plate Accumulation. Controlled Random Blind Clinical Study.
Conditions
-----------------
Periimplantitis
Intervention / Treatment
-----------------
* Drug: Chlorhexidine
* Other: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Good systemic health status (ASA I or II). No current pain. No use of painkillers or Anti-inflammatory drugs in the prior weeks. Older than 18 years. Oral hygiene index of ≤ 2 (Löe and Silness). A minimum of 2 mm of adhered gum. A minimum of 8 mm of vertical bone. A minimum of 7 mm of vestibule-lingual bone. Scheduled to receive a unitary implant. Willing to participate in this controlled study. Exclusion Criteria: Pregnant or nursing women. Use of any type of medication that might affect the perception of pain. An history of alcohol or drug abuse. A requirement for guided regeneration or sinus lifting procedures. Failure to comply with the study protocol.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: After the first week, the healling abutment will be randomly distributed in a test group with application of chlorhexidine gel or a control group without the application of the chlorhexidine gel.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Test (clorhexidine gel)<br>The healing abutments were covered by a chlorhexidine gel after the first week of the second surgery (2-stage implants). | Drug: Chlorhexidine<br>* Healing abutment with Clorhexidine<br>* Other names: CHX;|
| Placebo Comparator: Placebo<br>The healing abutments were covered without any antiseptic gel after the first week of the second surgery (2-stage implants). | Other: Placebo<br>* Healing abutment without any antiseptic<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of inflammation | Degree of inflammation was measured using a 4-point Likert scaleInflammation 0 = non-inflamed gingiva with pale pink color. Inflammation 1 = erythematous gingiva without bleeding on manipulation. Inflammation 2 = gingiva with slight bleeding during manipulation during unscrewing or screwing of the abutment. Inflammation 3 = gingiva with heavy bleeding during manipulation during unscrewing or screwing of the abutment. | 1 month after second surgery |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chlorhexidine, dental implant, in-situ drug delivery,
|
|
NCT03073954
|
Working Memory Training in COPD Patients: the Cogtrain-Trial
|
General cognitive impairment is highly prevalent in chronic obstructive pulmonary disease (COPD) patients. Domain-specific cognitive impairments include deficits in domains such as cognitive flexibility, verbal memory, working memory, planning, and psychomotor speed; which in general are associated with poor health behaviours, such as infrequent exercising and poor diet. Additional cognitive training may reverse these effects. Recent evidence suggests that working memory training is linked to self-control and, indirectly, to improved lifestyle behaviour including increased physical activity. The investigators hypothesise that enhancing cognitive performance through administering specific working memory training not only improves cognitive function but that it facilitates better adherence to a more active lifestyle and a healthier diet in COPD patients.
|
The Feasibility of Working Memory Training in COPD Patients and the Efficacy on Cognitive Performance, Self-Control and Stress Response
|
COPD, Cognitive Impairment
|
* Other: Working memory training
* Behavioral: Standardised healthy lifestyle coaching
|
Inclusion Criteria:~primary diagnosis of COPD based on the Global Initiative for Chronic obstructive Lung Disease (GOLD) guidelines~Patients also need to provide written informed consent~Be motivated as evaluated by the self-determination questionnaire~Exclusion Criteria:~Disease and or disability limiting the ability to undergo a neuropsychological testing battery and/or to follow a working memory training (e.g., blindness)~Neurological disorders (e.g., Alzheimer's Disease or cerebrovascular disease)~Insufficient mastery of the Dutch language~Individuals who during the study period are or will be participating in a PR programme
|
18 Years
| null |
All
|
No
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of the cognitive training in COPD patients as measured through training compliance. | The compliance as well as the acceptability of working memory training in the COPD patient population will be investigated | 6 months |
| Change in cognitive performance before and after working memory training as assessed through a cognitive test performance battery. | Improvement in cognitive flexibility, planning, and working memory. | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-control (impulsivity) | This will be measured using the stop signal task. | 6 months |
| Chronic stress levels as measured through hair levels of cortisol | An objective measure of stress levels experienced over the last 3 months will be measured using cortisol extracted from a hair sample. | 6 months |
| Stress levels as measured through the salivary cortisol awakening response | An objective measure of stress will be measured using salivary cortisol awakening response | 6 months |
| Stress perception as assessed through a perceived stress scale. | A subjective measure of chronic stress will be measured using the perceived stress scale score. | 6 months |
| Acute stress as assessed through the socially evaluated cold pressor test | Acute stress will be measured using the socially evaluated cold pressor test, heart rate is also monitored. | 6 months |
| Daily physical activity level | Physical activity data will be collected by an accelerometer using step counts. | 6 months |
| Mental health, depressive symptoms assessed via the BDI-II | Mental health with respect to depression will be evaluated using the Beck Depression Inventory-second edition (BDI-II) | 6 months |
| Mental health, anxiety symptoms assessed via the GAD-7 | Mental health with respect to anxiety will be evaluated using the Generalised Anxiety Disorder 7 (GAD-7) | 6 months |
| Physical performance assessed through the 6 minute walk test | Changes in physical performance will be assessed using the 6-minute walking test (6MWT).Two six-minute walk tests (6MWT) will be performed according to ERS/ATS guidelines to measure functional exercise capacity. The best 6MWT will be expressed in percentage of predicted values. | 6 months |
| Self-determination questionnaire | Motivation will be prior to the enrolment of participants in this study in order to include patients who are motivated to initiate and continue our working memory training. The self-made questionnaire evaluates patient's reasons for participating in the study in order to assess their intrinsic motivation. | 6 months |
| Short Performance Battery | The SPPB consists of three types of physical manoeuvres: the balance tests, the gait speed test, and the chair stand test. The results of the different tests result in a score which will be used for analysis. | 6 months |
| Changes in dietary intake over the intervention period | Changes in dietary intake over the intervention period will be assessed using a food frequency questionnaire. | 6 months |
| Medication adherence | Medication adherence will be measured using a sem | 6 months |
| Regulation of Eating Behavior Scale (REBS) | Changes in eating behavior motivation will be investigated using the REBS. | 6 months |
| Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2) Regulation | Changes in exercise motivation will be investigated using the BREQ-2 | 6 months |
| COPD Assessment test (CAT) | Impact of the intervention on quality of life will be done using the brief CAT questionnaire. | 6 months |
| Anthropometry | Alterations in Anthropometical measures will be evaluated using waist circumference, biometric impedance, and body weight (BMI). | 6 months |
| Manipulation Check | Participants will be asked to recall key health messages from their personalized healthy lifestyle advice sessions. Responses will be scored as follows: 0 points - field blank or no recall of the message content; 1 point - key points not directly related to the message themes; 2 points - key points directly related to the message themes. | 6 months |
|
Health Behavior, Executive function, Working-memory training, Feasibility, Impulsivity
|
Cognitive Dysfunction, Cognition Disorders, Neurocognitive Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Working memory training<br>Working memory training that increases with difficulty if participants answer two subsequent questions correctly, and standardised healthy lifestyle coaching. | Other: Working memory training<br>* The working memory intervention training programme consists of a domain-general cognitive working memory training programme. One training session will take 20 to 30 minutes, and participants will have to complete approximately 40 cognitive training sessions.~The sham treatment is the same as the intervention training however it does not increase in difficulty. Participants are presented with the same task at the same level of difficulty over and over again. Thus a training effect is not expected.<br>Behavioral: Standardised healthy lifestyle coaching<br>* Participants will receive standardised healthy living coaching focusing on healthy diet and daily physical activity.<br>|
| Sham Comparator: Sham working memory training<br>Working memory training that does not increase in difficulty, and standardised healthy lifestyle coaching. | Other: Working memory training<br>* The working memory intervention training programme consists of a domain-general cognitive working memory training programme. One training session will take 20 to 30 minutes, and participants will have to complete approximately 40 cognitive training sessions.~The sham treatment is the same as the intervention training however it does not increase in difficulty. Participants are presented with the same task at the same level of difficulty over and over again. Thus a training effect is not expected.<br>Behavioral: Standardised healthy lifestyle coaching<br>* Participants will receive standardised healthy living coaching focusing on healthy diet and daily physical activity.<br>|
|
Working Memory Training in COPD Patients: the Cogtrain-Trial
Study Overview
=================
Brief Summary
-----------------
General cognitive impairment is highly prevalent in chronic obstructive pulmonary disease (COPD) patients. Domain-specific cognitive impairments include deficits in domains such as cognitive flexibility, verbal memory, working memory, planning, and psychomotor speed; which in general are associated with poor health behaviours, such as infrequent exercising and poor diet. Additional cognitive training may reverse these effects. Recent evidence suggests that working memory training is linked to self-control and, indirectly, to improved lifestyle behaviour including increased physical activity. The investigators hypothesise that enhancing cognitive performance through administering specific working memory training not only improves cognitive function but that it facilitates better adherence to a more active lifestyle and a healthier diet in COPD patients.
Official Title
-----------------
The Feasibility of Working Memory Training in COPD Patients and the Efficacy on Cognitive Performance, Self-Control and Stress Response
Conditions
-----------------
COPD, Cognitive Impairment
Intervention / Treatment
-----------------
* Other: Working memory training
* Behavioral: Standardised healthy lifestyle coaching
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: primary diagnosis of COPD based on the Global Initiative for Chronic obstructive Lung Disease (GOLD) guidelines Patients also need to provide written informed consent Be motivated as evaluated by the self-determination questionnaire Exclusion Criteria: Disease and or disability limiting the ability to undergo a neuropsychological testing battery and/or to follow a working memory training (e.g., blindness) Neurological disorders (e.g., Alzheimer's Disease or cerebrovascular disease) Insufficient mastery of the Dutch language Individuals who during the study period are or will be participating in a PR programme
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Working memory training<br>Working memory training that increases with difficulty if participants answer two subsequent questions correctly, and standardised healthy lifestyle coaching. | Other: Working memory training<br>* The working memory intervention training programme consists of a domain-general cognitive working memory training programme. One training session will take 20 to 30 minutes, and participants will have to complete approximately 40 cognitive training sessions. The sham treatment is the same as the intervention training however it does not increase in difficulty. Participants are presented with the same task at the same level of difficulty over and over again. Thus a training effect is not expected.<br>Behavioral: Standardised healthy lifestyle coaching<br>* Participants will receive standardised healthy living coaching focusing on healthy diet and daily physical activity.<br>|
| Sham Comparator: Sham working memory training<br>Working memory training that does not increase in difficulty, and standardised healthy lifestyle coaching. | Other: Working memory training<br>* The working memory intervention training programme consists of a domain-general cognitive working memory training programme. One training session will take 20 to 30 minutes, and participants will have to complete approximately 40 cognitive training sessions. The sham treatment is the same as the intervention training however it does not increase in difficulty. Participants are presented with the same task at the same level of difficulty over and over again. Thus a training effect is not expected.<br>Behavioral: Standardised healthy lifestyle coaching<br>* Participants will receive standardised healthy living coaching focusing on healthy diet and daily physical activity.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of the cognitive training in COPD patients as measured through training compliance. | The compliance as well as the acceptability of working memory training in the COPD patient population will be investigated | 6 months |
| Change in cognitive performance before and after working memory training as assessed through a cognitive test performance battery. | Improvement in cognitive flexibility, planning, and working memory. | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-control (impulsivity) | This will be measured using the stop signal task. | 6 months |
| Chronic stress levels as measured through hair levels of cortisol | An objective measure of stress levels experienced over the last 3 months will be measured using cortisol extracted from a hair sample. | 6 months |
| Stress levels as measured through the salivary cortisol awakening response | An objective measure of stress will be measured using salivary cortisol awakening response | 6 months |
| Stress perception as assessed through a perceived stress scale. | A subjective measure of chronic stress will be measured using the perceived stress scale score. | 6 months |
| Acute stress as assessed through the socially evaluated cold pressor test | Acute stress will be measured using the socially evaluated cold pressor test, heart rate is also monitored. | 6 months |
| Daily physical activity level | Physical activity data will be collected by an accelerometer using step counts. | 6 months |
| Mental health, depressive symptoms assessed via the BDI-II | Mental health with respect to depression will be evaluated using the Beck Depression Inventory-second edition (BDI-II) | 6 months |
| Mental health, anxiety symptoms assessed via the GAD-7 | Mental health with respect to anxiety will be evaluated using the Generalised Anxiety Disorder 7 (GAD-7) | 6 months |
| Physical performance assessed through the 6 minute walk test | Changes in physical performance will be assessed using the 6-minute walking test (6MWT).Two six-minute walk tests (6MWT) will be performed according to ERS/ATS guidelines to measure functional exercise capacity. The best 6MWT will be expressed in percentage of predicted values. | 6 months |
| Self-determination questionnaire | Motivation will be prior to the enrolment of participants in this study in order to include patients who are motivated to initiate and continue our working memory training. The self-made questionnaire evaluates patient's reasons for participating in the study in order to assess their intrinsic motivation. | 6 months |
| Short Performance Battery | The SPPB consists of three types of physical manoeuvres: the balance tests, the gait speed test, and the chair stand test. The results of the different tests result in a score which will be used for analysis. | 6 months |
| Changes in dietary intake over the intervention period | Changes in dietary intake over the intervention period will be assessed using a food frequency questionnaire. | 6 months |
| Medication adherence | Medication adherence will be measured using a sem | 6 months |
| Regulation of Eating Behavior Scale (REBS) | Changes in eating behavior motivation will be investigated using the REBS. | 6 months |
| Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2) Regulation | Changes in exercise motivation will be investigated using the BREQ-2 | 6 months |
| COPD Assessment test (CAT) | Impact of the intervention on quality of life will be done using the brief CAT questionnaire. | 6 months |
| Anthropometry | Alterations in Anthropometical measures will be evaluated using waist circumference, biometric impedance, and body weight (BMI). | 6 months |
| Manipulation Check | Participants will be asked to recall key health messages from their personalized healthy lifestyle advice sessions. Responses will be scored as follows: 0 points - field blank or no recall of the message content; 1 point - key points not directly related to the message themes; 2 points - key points directly related to the message themes. | 6 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Health Behavior, Executive function, Working-memory training, Feasibility, Impulsivity
|
|
NCT01086215
|
Registry of AngioJet Use in the Peripheral Vascular System
|
The Registry involves the collection of information for research and educational purposes only on the use of AngioJet in the peripheral vascular system.
|
The PEARL II Registry is a prospective, multi-center, observational registry including 500 patients who meet eligibility from up to 50 sites worldwide. Patient participation will be 12 months including post procedure follow-up contact at 3, 6 and 12 months. The study duration is estimated at 36 months.~A patient's treatment is determined by the treating physician based on the clinical situation and local practices. In contrast to a randomized, controlled trial, there are no pre-defined experimental interventions.
|
PEARL II: PEripheral Use of AngioJet® Rheolytic Thrombectomy With a Variety of Catheter Lengths
|
Peripheral Vascular Disease, Embolism and Thrombosis, Venous Thrombosis
|
Inclusion Criteria:~Patient has been treated in the peripheral vascular system with any of the AngioJet System catheters.~Patient has provided appropriate consent/authorization per the site's institutional policy and procedure.~Exclusion Criteria:~Patient has previously been enrolled in either the PEARL Registry or the PEARL II Registry in the last 12months.
| null | null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Degree of Occlusion From Baseline to Final Angiogram/Venogram. | From the Index Procedure's Baseline (pre-endovascular treatment) and Final (post-endovascular treatment) angiograms/venograms, each vessel was assigned a value by the treating physician.~complete occlusion (>90% occlusion);~substantial occlusion (50-90% occlusion OR <50% occlusion and >3cm in length);~partial occlusion (<50% occlusion AND <3cm in length)~patent (without visable thrombus or occlusion) The levels of change (improvement) were calculated by subtracting the baseline assigned angiographic/venographic value from the final value. | Day 1 |
| Rethrombosis | The number of patients affected by rethrombosis of the treated vessels (first episode) throughout a 12 Month Follow-Up. | 3 Month , 6 Month and 12 Month Follow Up |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concomitant Treatments Used With the AngioJet® System | The # of patients exposed to each treatment option at least once in the given thrombotic condition during the Index Procedure | Day 1 |
|
Thrombosis, Embolism, Vascular Diseases, Venous Thrombosis, Peripheral Vascular Diseases, Peripheral Arterial Disease, Embolism and Thrombosis, Cardiovascular Diseases, Atherosclerosis, Arteriosclerosis, Arterial Occlusive Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Limb Ischemia<br>Patients presenting with limb ischemia for treatment | |
| Deep Vein Thrombosis<br>Patients presenting with deep vein thrombosis for treatment | |
| Hemodialysis Access<br>Patients presenting with thrombosed hemodialysis access for treatment | |
| Other Thrombotic Conditions<br>Patients presenting with a thrombotic condition other than limb ischemia, deep vein thrombosis or thrombosed hemodialysis access for treatment | |
|
Registry of AngioJet Use in the Peripheral Vascular System
Study Overview
=================
Brief Summary
-----------------
The Registry involves the collection of information for research and educational purposes only on the use of AngioJet in the peripheral vascular system.
Detailed Description
-----------------
The PEARL II Registry is a prospective, multi-center, observational registry including 500 patients who meet eligibility from up to 50 sites worldwide. Patient participation will be 12 months including post procedure follow-up contact at 3, 6 and 12 months. The study duration is estimated at 36 months. A patient's treatment is determined by the treating physician based on the clinical situation and local practices. In contrast to a randomized, controlled trial, there are no pre-defined experimental interventions.
Official Title
-----------------
PEARL II: PEripheral Use of AngioJet® Rheolytic Thrombectomy With a Variety of Catheter Lengths
Conditions
-----------------
Peripheral Vascular Disease, Embolism and Thrombosis, Venous Thrombosis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient has been treated in the peripheral vascular system with any of the AngioJet System catheters. Patient has provided appropriate consent/authorization per the site's institutional policy and procedure. Exclusion Criteria: Patient has previously been enrolled in either the PEARL Registry or the PEARL II Registry in the last 12months.
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Limb Ischemia<br>Patients presenting with limb ischemia for treatment | |
| Deep Vein Thrombosis<br>Patients presenting with deep vein thrombosis for treatment | |
| Hemodialysis Access<br>Patients presenting with thrombosed hemodialysis access for treatment | |
| Other Thrombotic Conditions<br>Patients presenting with a thrombotic condition other than limb ischemia, deep vein thrombosis or thrombosed hemodialysis access for treatment | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Degree of Occlusion From Baseline to Final Angiogram/Venogram. | From the Index Procedure's Baseline (pre-endovascular treatment) and Final (post-endovascular treatment) angiograms/venograms, each vessel was assigned a value by the treating physician. complete occlusion (>90% occlusion); substantial occlusion (50-90% occlusion OR <50% occlusion and >3cm in length); partial occlusion (<50% occlusion AND <3cm in length) patent (without visable thrombus or occlusion) The levels of change (improvement) were calculated by subtracting the baseline assigned angiographic/venographic value from the final value. | Day 1 |
| Rethrombosis | The number of patients affected by rethrombosis of the treated vessels (first episode) throughout a 12 Month Follow-Up. | 3 Month , 6 Month and 12 Month Follow Up |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concomitant Treatments Used With the AngioJet® System | The # of patients exposed to each treatment option at least once in the given thrombotic condition during the Index Procedure | Day 1 |
|
|||
NCT05318209
|
Effect of Closed-chain Shoulder Girdle Scapular Depression Exercise on Shoulder Impingement Syndrome
|
forty patients will be assigned randomly into 2 equal groups Study group (n=23) will receive closed-chain shoulder girdle scapular depression exercise in addition to Stretching for posterior capsule & pectoralis minor, Eccentric exercise for external rotators and Strength exercises for serrates anterior and low intensity ultrasound Control group B (n=23) will receive shoulder girdle depression against manual resistance exercise in addition to stretching for posterior capsule & pectoralis minor, eccentric exercise for external rotators and Strength exercises for serrates anterior and low intensity ultrasound .~The exercise program will consist of 3 sessions / week for 5 weeks
|
BACKGROUND:~Patients with shoulder impingment syndrome report disability, especially during overhead movements, which may hinder activities of daily living .~Muscular strengthening training influences the resting position and scapular movement pattern of subjects with shoulder impingement syndrome and improve function of the affected shoulder.~Therefore, the focus of treatment for the syndrome is on performing exercises, including stretching, strengthening, and neuromuscular control exercises.~Although multiple types of exercise, such as scapular stability exercises, strengthening of the rotator cuff through range, and flexibility exercises for the anterior and posterior shoulder exercise is effective in the management of patients with shoulder impingement syndrome, there is not enough evidence to say whether one mode of exercise is superior to another.~RESEARCH QUESTION:~Are there any difference between closed-chain shoulder girdle scapular depression exercise and shoulder girdle depression against manual resistance exercise on patients with shoulder impingement syndrome~METHODS:~forty patients will be assigned randomly into 2 equal groups Study group (n=23) will receive closed-chain shoulder girdle scapular depression exercise in addition to Stretching for posterior capsule & pectoralis minor, Eccentric exercise for external rotators and Strength exercises for serrates anterior and low intensity ultrasound Control group B (n=23) will receive shoulder girdle depression against manual resistance exercise in addition to stretching for posterior capsule & pectoralis minor, eccentric exercise for external rotators and Strength exercises for serrates anterior and low intensity ultrasound .~The exercise program will consist of 3 sessions / week for 5 weeks
|
Comparison Between Closed-chain Shoulder Girdle Scapular Depression Exercise and Shoulder Girdle Depression Against Manual Resistance on Patients With Shoulder Impingement Syndrome
|
Shoulder Impingement Syndrome
|
* Other: Exercise
|
Inclusion Criteria:~Patients aged from 25 to 45 years old.~Patients with shoulder impingement stage I &II as judged by criteria of neer classification.~Patients diagnosed by orthopedic surgeon with shoulder impingement, the diagnosis will be confirmed by positive Neer and Hawkins tests.~Exclusion Criteria:~History of cardiac diseases or dyspnea on exertion~Patients with cervical radiculopathy.~Patients with shoulder instability.~Patients with frozen shoulder.~Acute shoulder trauma.
|
25 Years
|
45 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain will be measured by visual analogue scale | 10cm visual analogue scale (0= no pain, and 10= maximum pain) will be used to determine overall shoulder pain | 10 minutes |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Range of motion (flexion and abduction) will be measured by Electronic goniometer | Electronic Goniometer will be used to measure shoulder range of motion (Flexion and abduction) | 20 minutes |
| Function | shoulder function will be measured by western Ontario Rotator Cuff Questionnaire (WORC). | 30 minutes |
|
Shoulder Impingement Syndrome, Syndrome, Rotator Cuff Injuries, Depression, Disease, Pathologic Processes, Behavioral Symptoms, Rupture, Wounds and Injuries, Shoulder Injuries, Tendon Injuries, Joint Diseases, Musculoskeletal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study grou[p<br>Closed-chain shoulder girdle scapular depression exercise | Other: Exercise<br>* Closed-chain Shoulder Girdle Scapular Depression Exercise<br>|
| Active Comparator: control group<br>Shoulder girdle depression against manual resistance exercise | Other: Exercise<br>* Closed-chain Shoulder Girdle Scapular Depression Exercise<br>|
|
Effect of Closed-chain Shoulder Girdle Scapular Depression Exercise on Shoulder Impingement Syndrome
Study Overview
=================
Brief Summary
-----------------
forty patients will be assigned randomly into 2 equal groups Study group (n=23) will receive closed-chain shoulder girdle scapular depression exercise in addition to Stretching for posterior capsule & pectoralis minor, Eccentric exercise for external rotators and Strength exercises for serrates anterior and low intensity ultrasound Control group B (n=23) will receive shoulder girdle depression against manual resistance exercise in addition to stretching for posterior capsule & pectoralis minor, eccentric exercise for external rotators and Strength exercises for serrates anterior and low intensity ultrasound . The exercise program will consist of 3 sessions / week for 5 weeks
Detailed Description
-----------------
BACKGROUND: Patients with shoulder impingment syndrome report disability, especially during overhead movements, which may hinder activities of daily living . Muscular strengthening training influences the resting position and scapular movement pattern of subjects with shoulder impingement syndrome and improve function of the affected shoulder. Therefore, the focus of treatment for the syndrome is on performing exercises, including stretching, strengthening, and neuromuscular control exercises. Although multiple types of exercise, such as scapular stability exercises, strengthening of the rotator cuff through range, and flexibility exercises for the anterior and posterior shoulder exercise is effective in the management of patients with shoulder impingement syndrome, there is not enough evidence to say whether one mode of exercise is superior to another. RESEARCH QUESTION: Are there any difference between closed-chain shoulder girdle scapular depression exercise and shoulder girdle depression against manual resistance exercise on patients with shoulder impingement syndrome METHODS: forty patients will be assigned randomly into 2 equal groups Study group (n=23) will receive closed-chain shoulder girdle scapular depression exercise in addition to Stretching for posterior capsule & pectoralis minor, Eccentric exercise for external rotators and Strength exercises for serrates anterior and low intensity ultrasound Control group B (n=23) will receive shoulder girdle depression against manual resistance exercise in addition to stretching for posterior capsule & pectoralis minor, eccentric exercise for external rotators and Strength exercises for serrates anterior and low intensity ultrasound . The exercise program will consist of 3 sessions / week for 5 weeks
Official Title
-----------------
Comparison Between Closed-chain Shoulder Girdle Scapular Depression Exercise and Shoulder Girdle Depression Against Manual Resistance on Patients With Shoulder Impingement Syndrome
Conditions
-----------------
Shoulder Impingement Syndrome
Intervention / Treatment
-----------------
* Other: Exercise
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged from 25 to 45 years old. Patients with shoulder impingement stage I &II as judged by criteria of neer classification. Patients diagnosed by orthopedic surgeon with shoulder impingement, the diagnosis will be confirmed by positive Neer and Hawkins tests. Exclusion Criteria: History of cardiac diseases or dyspnea on exertion Patients with cervical radiculopathy. Patients with shoulder instability. Patients with frozen shoulder. Acute shoulder trauma.
Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 45 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study grou[p<br>Closed-chain shoulder girdle scapular depression exercise | Other: Exercise<br>* Closed-chain Shoulder Girdle Scapular Depression Exercise<br>|
| Active Comparator: control group<br>Shoulder girdle depression against manual resistance exercise | Other: Exercise<br>* Closed-chain Shoulder Girdle Scapular Depression Exercise<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain will be measured by visual analogue scale | 10cm visual analogue scale (0= no pain, and 10= maximum pain) will be used to determine overall shoulder pain | 10 minutes |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Range of motion (flexion and abduction) will be measured by Electronic goniometer | Electronic Goniometer will be used to measure shoulder range of motion (Flexion and abduction) | 20 minutes |
| Function | shoulder function will be measured by western Ontario Rotator Cuff Questionnaire (WORC). | 30 minutes |
|
|
NCT04144114
|
The Effect of ProHydrolase® on the Amino Acid, Intramuscular Anabolic Signaling, and Endocrine Response to Resistance Exercise in Trained Males
|
To examine the amino acid absorption following acute resistance exercise between three supplemental treatments: 1) Whey Protein + ProHydrolase (WPH) 2) Whey Protein (W) and 3) Non-Caloric Placebo (PL). To examine three supplemental treatments (WPH, W, PL) in conjunction with acute resistance exercise on the mTORC1 complex pathway. To examine three supplemental treatments (WPH, W, PL) in conjunction with acute resistance exercise on circulating concentrations of endocrine biomarkers.
|
The Effect of ProHydrolase® on the Amino Acid, Intramuscular Anabolic Signaling, and Endocrine Response to Resistance Exercise in Trained Males
|
Amino Acids
|
* Dietary Supplement: ProHydrolase®
* Dietary Supplement: Whey protein
* Dietary Supplement: Placebo
|
Inclusion Criteria:~• At least one-year of resistance training experience~Free of any physical limitations (determined by health and activity questionnaire).~Between the ages of 18 and 35.~Ability to leg press a weight equivalent to 1.5 times their body mass~Exclusion Criteria:~• Inability to perform physical exercise (determined by health and activity questionnaire)~Taking any other nutritional supplement or performance enhancing drug (determined from health and activity questionnaire).~Physical injury preventing the athlete from participating in offseason training~Any chronic illness that causes continuous medical care
|
18 Years
|
35 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amino acid absorption | To examine the amino acid absorption following acute resistance exercise between three supplemental treatments: 1) Whey Protein + ProHydrolase (WPH) 2) Whey Protein (W) and 3) Non-Caloric Placebo (PL) | 4 weeks |
| mTORC1 pathway | To examine three supplemental treatments (WPH, W, PL) in conjunction with acute resistance exercise on the mTORC1 complex pathway | 4 weeks |
| Endocrine markers | To examine three supplemental treatments (WPH, W, PL) in conjunction with acute resistance exercise on circulating concentrations of endocrine biomarkers. | 4 weeks |
|
Amino Acids, Intramuscular Anabolic Signaling, Endocrine Response, Resistance Training
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whey + ProHydrolase®<br>Subjects received 250mg of ProHydrolase® along with 25g of whey protein mixed in a drink every visit for 4 weeks | Dietary Supplement: ProHydrolase®<br>* Subjects received 250mg of ProHydrolase® with 25g whey protein mixed together in a drink<br>|
| Active Comparator: Whey<br>Subjects received 25g whey protein in a drink every visit for 4 weeks | Dietary Supplement: Whey protein<br>* Subjects received 25g of whey protein powder mixed to together in a drink<br>|
| Placebo Comparator: Placebo<br>Subjects received 25g maltodextrin in a drink every visit for 4 weeks | Dietary Supplement: Placebo<br>* Placebo<br>|
|
The Effect of ProHydrolase® on the Amino Acid, Intramuscular Anabolic Signaling, and Endocrine Response to Resistance Exercise in Trained Males
Study Overview
=================
Brief Summary
-----------------
To examine the amino acid absorption following acute resistance exercise between three supplemental treatments: 1) Whey Protein + ProHydrolase (WPH) 2) Whey Protein (W) and 3) Non-Caloric Placebo (PL). To examine three supplemental treatments (WPH, W, PL) in conjunction with acute resistance exercise on the mTORC1 complex pathway. To examine three supplemental treatments (WPH, W, PL) in conjunction with acute resistance exercise on circulating concentrations of endocrine biomarkers.
Official Title
-----------------
The Effect of ProHydrolase® on the Amino Acid, Intramuscular Anabolic Signaling, and Endocrine Response to Resistance Exercise in Trained Males
Conditions
-----------------
Amino Acids
Intervention / Treatment
-----------------
* Dietary Supplement: ProHydrolase®
* Dietary Supplement: Whey protein
* Dietary Supplement: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: • At least one-year of resistance training experience Free of any physical limitations (determined by health and activity questionnaire). Between the ages of 18 and 35. Ability to leg press a weight equivalent to 1.5 times their body mass Exclusion Criteria: • Inability to perform physical exercise (determined by health and activity questionnaire) Taking any other nutritional supplement or performance enhancing drug (determined from health and activity questionnaire). Physical injury preventing the athlete from participating in offseason training Any chronic illness that causes continuous medical care
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whey + ProHydrolase®<br>Subjects received 250mg of ProHydrolase® along with 25g of whey protein mixed in a drink every visit for 4 weeks | Dietary Supplement: ProHydrolase®<br>* Subjects received 250mg of ProHydrolase® with 25g whey protein mixed together in a drink<br>|
| Active Comparator: Whey<br>Subjects received 25g whey protein in a drink every visit for 4 weeks | Dietary Supplement: Whey protein<br>* Subjects received 25g of whey protein powder mixed to together in a drink<br>|
| Placebo Comparator: Placebo<br>Subjects received 25g maltodextrin in a drink every visit for 4 weeks | Dietary Supplement: Placebo<br>* Placebo<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amino acid absorption | To examine the amino acid absorption following acute resistance exercise between three supplemental treatments: 1) Whey Protein + ProHydrolase (WPH) 2) Whey Protein (W) and 3) Non-Caloric Placebo (PL) | 4 weeks |
| mTORC1 pathway | To examine three supplemental treatments (WPH, W, PL) in conjunction with acute resistance exercise on the mTORC1 complex pathway | 4 weeks |
| Endocrine markers | To examine three supplemental treatments (WPH, W, PL) in conjunction with acute resistance exercise on circulating concentrations of endocrine biomarkers. | 4 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Amino Acids, Intramuscular Anabolic Signaling, Endocrine Response, Resistance Training
|
|||
NCT04296149
|
Beta- Probe and Surgery in GEP NET: Evaluation of a New Probe
|
Radioguided surgery (RGS) with beta- radioisotopes is a novel approach focused on developing a new probe which, detecting electrons and operating with low background, provides a clearer delineation of the margins of lesions with low radiation exposition for surgeons.~To validate this procedure, ex vivo specimens of tumours expressing somatostatin receptors, as small-intestine neuroendocrine (SI-NET), will be tested
|
Small Intestinal neuroendocrine patients, with a positive Ga-68-DOTATOC PET/CT, will receive a small amount of beta- radiopharmaceutical (Y-90-DOTATOC), and then operated, as clinical indicated.~Tissue samples will be tested ex-vivo with a beta-probe prototype
|
Studio Esplorativo Monocentrico Non Controllato, in Aperto, Volto a Sviluppare e Valutare l'Applicazione di Una Tecnica Innovativa di Rimozione Radioguidata Dei Tumori Neuroendocrini Gastro-entero-pancreatici
|
Neuroendocrine Tumors
|
* Drug: Y90-DOTA-Tyr3-Octreotide
|
Inclusion Criteria:~SI NET patients, Ga-68-DOTATOC PET/CT positive, proposed for surgery~Exclusion Criteria:~negative PET/CT; pregnancy
|
18 Years
| null |
All
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of sensitivity of a beta- probe | after receiving a small amount of radioactivity, patients will be operated and an evaluation of radioactivity on surgical specimens will be evaluated | 2 years |
|
beta- probe, radioguided surgery
|
Octreotide, Edotreotide, Gastrointestinal Agents, Antineoplastic Agents, Hormonal, Antineoplastic Agents, Radiopharmaceuticals, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Y-90-DOTATOC<br>Patients affected by Small Intestine neuroendocrine tumors | Drug: Y90-DOTA-Tyr3-Octreotide<br>* Patients enrolled for surgery will receive a small amount of Y-90-DOTATOC, in order to check beta- radioactivity by the probe<br>* Other names: Beta- emetting radioisotope;|
|
Beta- Probe and Surgery in GEP NET: Evaluation of a New Probe
Study Overview
=================
Brief Summary
-----------------
Radioguided surgery (RGS) with beta- radioisotopes is a novel approach focused on developing a new probe which, detecting electrons and operating with low background, provides a clearer delineation of the margins of lesions with low radiation exposition for surgeons. To validate this procedure, ex vivo specimens of tumours expressing somatostatin receptors, as small-intestine neuroendocrine (SI-NET), will be tested
Detailed Description
-----------------
Small Intestinal neuroendocrine patients, with a positive Ga-68-DOTATOC PET/CT, will receive a small amount of beta- radiopharmaceutical (Y-90-DOTATOC), and then operated, as clinical indicated. Tissue samples will be tested ex-vivo with a beta-probe prototype
Official Title
-----------------
Studio Esplorativo Monocentrico Non Controllato, in Aperto, Volto a Sviluppare e Valutare l'Applicazione di Una Tecnica Innovativa di Rimozione Radioguidata Dei Tumori Neuroendocrini Gastro-entero-pancreatici
Conditions
-----------------
Neuroendocrine Tumors
Intervention / Treatment
-----------------
* Drug: Y90-DOTA-Tyr3-Octreotide
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: SI NET patients, Ga-68-DOTATOC PET/CT positive, proposed for surgery Exclusion Criteria: negative PET/CT; pregnancy
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Y-90-DOTATOC<br>Patients affected by Small Intestine neuroendocrine tumors | Drug: Y90-DOTA-Tyr3-Octreotide<br>* Patients enrolled for surgery will receive a small amount of Y-90-DOTATOC, in order to check beta- radioactivity by the probe<br>* Other names: Beta- emetting radioisotope;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of sensitivity of a beta- probe | after receiving a small amount of radioactivity, patients will be operated and an evaluation of radioactivity on surgical specimens will be evaluated | 2 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
beta- probe, radioguided surgery
|
|
NCT05065541
|
Positron Emission Tomography (PET) Imaging Study to Evaluate Enzyme Availability in the Central Nervous System Before and After CC-97489 Administration in Healthy Participants
|
The purpose of this study is to evaluate enzyme availability in the central nervous system before and after CC-97489 administration in healthy participants
|
A Phase 1, Open-label, Multi-part Positron Emission Tomography (PET) Imaging Study to Evaluate the Biodistribution and Radiation Dosimetry of the Monoacylglycerol Lipase (MGLL) PET Ligand [18F]T-401 and to Evaluate Fatty Acid Amide Hydrolase (FAAH) and MGLL Enzyme Availability in the Central Nervous System Using [11C]MK-3168 and [18F]T-401 PET Ligands Before and After Oral Administration of Single and Multiple Doses of CC-97489 in Healthy Adult Subjects
|
Healthy Volunteers
|
* Drug: CC-97489
* Drug: [18F]T-401
* Drug: [11C]MK-3168
|
Inclusion Criteria:~Has a Body Mass Index (BMI) of 18.0 to 33.0 kg/m^2, inclusive. BMI = weight (kg)/(height [m])^2~Must be healthy based on medical history, physical examination (PE), clinical laboratory test results, vital signs, and 12-lead electrocardiogram (ECG) at screening and check-in~Exclusion Criteria:~Has any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study~Is pregnant or breastfeeding~Is part of the study site staff personnel or a family member of the study site staff~Other protocol-defined inclusion/exclusion criteria apply
|
18 Years
|
55 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiation dosimetry calculated from PET-CT images | | 1 day |
| Calculated % Injected Dose in brain and other key organs and tissues | | 1 day |
| Calculated Standard Uptake Volume in brain and other key organs and tissues | | 1 day |
| Change from baseline in SUV in the brain based on PET scans | | Up to 14 days |
| Change from baseline in VT in the brain based on PET scans. | | Up to 14 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AEs | | Up to 28 days after the last dose |
| Incidence of serious adverse events (SAEs) | | Up to 28 days after the last dose |
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval | PR interval: The time from the onset of the P wave to the start of the QRS complex | Day 21 |
| Incidence of clinically significant changes in ECG parameters: QRS interval | QRS interval: A combination of the Q wave, R wave and S wave, the QRS complex represents ventricular depolarization. | Day 21 |
| Incidence of clinically significant changes in ECG parameters: QT interval | QT interval: Measured from the beginning of the QRS complex to the end of the T wave. | Day 21 |
| Incidence of clinically significant changes in ECG parameters: QTcF interval | QTcF interval: Corrected QT interval using Fridericia's formula (QTcF). | Day 21 |
| Incidence of clinically significant changes in vital signs: Body temperature | | Day 21 |
| Incidence of clinically significant changes in vital signs: Respiratory rate | | Day 21 |
| Incidence of clinically significant changes in vital signs: Blood pressure | | Day 21 |
| Incidence of clinically significant changes in vital signs: Heart rate | | Day 21 |
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests | | Up to Day 18 |
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests | | Up to Day 18 |
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests | | Up to Day 18 |
| Pharmacokinetics - Maximum observed plasma concentration (Cmax) | | Up to 19 days |
| Pharmacokinetics - Time to maximum observed plasma concentration (Tmax) | | Up to 19 days |
| Pharmacokinetics - Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-∞) | | Up to 19 days |
|
CC-97489, Healthy Adults, Phase 1, Positron Emission Tomography (PET) Imaging
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br> | Drug: [18F]T-401<br>* Specified dose on specified days<br>|
| Experimental: Part 2<br> | Drug: CC-97489<br>* Specified dose on specified days<br>Drug: [18F]T-401<br>* Specified dose on specified days<br>Drug: [11C]MK-3168<br>* Specified dose on specified days<br>|
| Experimental: Part 3<br> | Drug: CC-97489<br>* Specified dose on specified days<br>Drug: [18F]T-401<br>* Specified dose on specified days<br>|
|
Positron Emission Tomography (PET) Imaging Study to Evaluate Enzyme Availability in the Central Nervous System Before and After CC-97489 Administration in Healthy Participants
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate enzyme availability in the central nervous system before and after CC-97489 administration in healthy participants
Official Title
-----------------
A Phase 1, Open-label, Multi-part Positron Emission Tomography (PET) Imaging Study to Evaluate the Biodistribution and Radiation Dosimetry of the Monoacylglycerol Lipase (MGLL) PET Ligand [18F]T-401 and to Evaluate Fatty Acid Amide Hydrolase (FAAH) and MGLL Enzyme Availability in the Central Nervous System Using [11C]MK-3168 and [18F]T-401 PET Ligands Before and After Oral Administration of Single and Multiple Doses of CC-97489 in Healthy Adult Subjects
Conditions
-----------------
Healthy Volunteers
Intervention / Treatment
-----------------
* Drug: CC-97489
* Drug: [18F]T-401
* Drug: [11C]MK-3168
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Has a Body Mass Index (BMI) of 18.0 to 33.0 kg/m^2, inclusive. BMI = weight (kg)/(height [m])^2 Must be healthy based on medical history, physical examination (PE), clinical laboratory test results, vital signs, and 12-lead electrocardiogram (ECG) at screening and check-in Exclusion Criteria: Has any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study Is pregnant or breastfeeding Is part of the study site staff personnel or a family member of the study site staff Other protocol-defined inclusion/exclusion criteria apply
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br> | Drug: [18F]T-401<br>* Specified dose on specified days<br>|
| Experimental: Part 2<br> | Drug: CC-97489<br>* Specified dose on specified days<br>Drug: [18F]T-401<br>* Specified dose on specified days<br>Drug: [11C]MK-3168<br>* Specified dose on specified days<br>|
| Experimental: Part 3<br> | Drug: CC-97489<br>* Specified dose on specified days<br>Drug: [18F]T-401<br>* Specified dose on specified days<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiation dosimetry calculated from PET-CT images | | 1 day |
| Calculated % Injected Dose in brain and other key organs and tissues | | 1 day |
| Calculated Standard Uptake Volume in brain and other key organs and tissues | | 1 day |
| Change from baseline in SUV in the brain based on PET scans | | Up to 14 days |
| Change from baseline in VT in the brain based on PET scans. | | Up to 14 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AEs | | Up to 28 days after the last dose |
| Incidence of serious adverse events (SAEs) | | Up to 28 days after the last dose |
| Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval | PR interval: The time from the onset of the P wave to the start of the QRS complex | Day 21 |
| Incidence of clinically significant changes in ECG parameters: QRS interval | QRS interval: A combination of the Q wave, R wave and S wave, the QRS complex represents ventricular depolarization. | Day 21 |
| Incidence of clinically significant changes in ECG parameters: QT interval | QT interval: Measured from the beginning of the QRS complex to the end of the T wave. | Day 21 |
| Incidence of clinically significant changes in ECG parameters: QTcF interval | QTcF interval: Corrected QT interval using Fridericia's formula (QTcF). | Day 21 |
| Incidence of clinically significant changes in vital signs: Body temperature | | Day 21 |
| Incidence of clinically significant changes in vital signs: Respiratory rate | | Day 21 |
| Incidence of clinically significant changes in vital signs: Blood pressure | | Day 21 |
| Incidence of clinically significant changes in vital signs: Heart rate | | Day 21 |
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests | | Up to Day 18 |
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests | | Up to Day 18 |
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests | | Up to Day 18 |
| Pharmacokinetics - Maximum observed plasma concentration (Cmax) | | Up to 19 days |
| Pharmacokinetics - Time to maximum observed plasma concentration (Tmax) | | Up to 19 days |
| Pharmacokinetics - Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-∞) | | Up to 19 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CC-97489, Healthy Adults, Phase 1, Positron Emission Tomography (PET) Imaging
|
||
NCT03442153
|
Comparative Efficacy and Tolerability of No7 in Osteoarthritis of the Knee
|
This study evaluates the effect of dietary supplement Solgar No7 in 76 adult Osteoarthritis of the Knee Patients, while the other half will receive placebo.
|
Solgar No7 is a Dietary Supplement marketed in Israel on a regular basis with the approval of the Israeli Ministry of Health. The product is based on Herbal Extracts and Vitamins. The individual components of the product were effective in some studies in relieving pain and inflammation in such patients. This Study evaluates the effect of these components as a complex.
|
Comparative Efficacy and Tolerability of No7 in Osteoarthritis of the Knee: A Double Blind, Randomized, Placebo Controlled Clinical Study
|
Osteoarthritis, Knee
|
* Dietary Supplement: Solgar No7 Complex
* Dietary Supplement: placebo
|
Inclusion Criteria:~Osteoarthritis (at least 2-nd grade according to Kellgren Classification)~Ability to walk independently~Pain Intensity of 4 or more according to Visual Analogue Scale~NSAIDs usage of 5 times or more per month during 3 months before the intervention~Ability to understand the benefits and risks of the proposed treatment and can provide answers to the required questions and fill out a questionnaire in Hebrew~Early consent of participants not to start a new treatment for Osteoarthritis including medication, surgery, physiotherapy, laser therapy, etc. during the period of the study (3 months) - except for a clear medical need (should report to the investigators immediately)~Exclusion Criteria:~Inflammatory Arthropathy, Severe Rheumatoid Arthritis, Psoriatic Arthritis or Gout~History of injection of pharmacological material (steroids, anesthetic, hyaluronic acid or any other pharmacological substance) into the knee joint during the six months prior to the start of the study~Taking of biological drugs that may affect inflammatory conditions (such as anti-TNF- alpha, etc.) or oral PO steroids - even if given to another disease, for more than 5 days during 3 months prior to the start of the study~Chronic administration of any anti-inflammatory drug during the study period and / or at least one month prior to commencement of the study.~Chronic administration of medical cannabis~Use of analgetics in a formulation that provides a half-life of over 24 hours (eg, Butrans, Fentanyl)~Chronic use of vitamin K antagonists, Heparin, Enoxaparin~Injury to the knee during six months prior to the experiment~Expectations of surgical intervention, physiotherapy or other treatment of osteoarthritis before the end of the study period~Significant irregularities in renal or liver function, active malignant disease in the last 3 years, heart failure, uncontrolled hypertension, active peptic ulcer, hematologic diseases, severe neurological diseases, and mental illness with seizures in the last two years.~Peripheral neuropathy that treated by any drug~High alcohol consumption (over 2 standard doses per day)~Sensitivity to one of the ingredients and / or sensitivity to NSAIDs. It is Possible to include a patient who is sensitive to a specific drug from the family of NSAIDs, but can take other drugs from this family.~Any medical condition or treatment which, in the opinion of the investigators, may mask the results of the study and / or interfere with the research questions and / or terminate the research properly and / or endanger the participant in any way during the course of the study.
|
45 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The product in not drug or medical device (but a dietary supplement). There are 76 participants divided inti 2 groups : experimental group (38) and Placebo group (38). The period of the intervention: 90 days
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity | Self reported pain intensity in the scale 1-10 | Pain intensity Reported to the Doctor after one month of the treatment. Each item is scored 0-10 (0=no pain; 10=pain as bad as can be), yielding a total between 0 and 30. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee Stiffness | The stiffness of the knee according to the doctor evaluation | nee Stiffness checked by the Doctor after one month of treatment. Each item is scored 0-10 (0=no pain; 10=pain as bad as can be), yielding a total between 0 and 30 |
| Non Steroidal Anti Inflammatory Drugs Usage | Self reported Non Steroidal Anti Inflammatory Drugs Usage | Pain Medication Usage as Reported to the Doctor after one month of treatment. Each item is scored as a number of the dose units that were used during the all period (0=no medications, 1=only one dose of medication etc) |
| Adverse Reactions | Self reported Adverse Reactions | Adverse Reactions as Reported to the Doctor over the period of the treatment. Each item is scored as a number of the dose units that were used during the all period (0=no adverse reactions, 1=only one adverse reaction etc) |
|
Rheumatic Diseases, Osteoarthritis, Osteoarthritis, Knee, Arthritis, Joint Diseases, Musculoskeletal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Solgar No7<br>Aflapin 100 mg and Collagen UC2 40 mg by mouth every 24 hours for 90 days | Dietary Supplement: Solgar No7 Complex<br>* Solgar No7 Capsules<br>|
| Placebo Comparator: Placebo for Solgar No7<br>Placebo 1 Capsule by mouth, every 24 hours for 90 days | Dietary Supplement: placebo<br>* Placebo tablets Cellulose<br>* Other names: Placebo for Solgar No7;|
|
Comparative Efficacy and Tolerability of No7 in Osteoarthritis of the Knee
Study Overview
=================
Brief Summary
-----------------
This study evaluates the effect of dietary supplement Solgar No7 in 76 adult Osteoarthritis of the Knee Patients, while the other half will receive placebo.
Detailed Description
-----------------
Solgar No7 is a Dietary Supplement marketed in Israel on a regular basis with the approval of the Israeli Ministry of Health. The product is based on Herbal Extracts and Vitamins. The individual components of the product were effective in some studies in relieving pain and inflammation in such patients. This Study evaluates the effect of these components as a complex.
Official Title
-----------------
Comparative Efficacy and Tolerability of No7 in Osteoarthritis of the Knee: A Double Blind, Randomized, Placebo Controlled Clinical Study
Conditions
-----------------
Osteoarthritis, Knee
Intervention / Treatment
-----------------
* Dietary Supplement: Solgar No7 Complex
* Dietary Supplement: placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Osteoarthritis (at least 2-nd grade according to Kellgren Classification) Ability to walk independently Pain Intensity of 4 or more according to Visual Analogue Scale NSAIDs usage of 5 times or more per month during 3 months before the intervention Ability to understand the benefits and risks of the proposed treatment and can provide answers to the required questions and fill out a questionnaire in Hebrew Early consent of participants not to start a new treatment for Osteoarthritis including medication, surgery, physiotherapy, laser therapy, etc. during the period of the study (3 months) - except for a clear medical need (should report to the investigators immediately) Exclusion Criteria: Inflammatory Arthropathy, Severe Rheumatoid Arthritis, Psoriatic Arthritis or Gout History of injection of pharmacological material (steroids, anesthetic, hyaluronic acid or any other pharmacological substance) into the knee joint during the six months prior to the start of the study Taking of biological drugs that may affect inflammatory conditions (such as anti-TNF- alpha, etc.) or oral PO steroids - even if given to another disease, for more than 5 days during 3 months prior to the start of the study Chronic administration of any anti-inflammatory drug during the study period and / or at least one month prior to commencement of the study. Chronic administration of medical cannabis Use of analgetics in a formulation that provides a half-life of over 24 hours (eg, Butrans, Fentanyl) Chronic use of vitamin K antagonists, Heparin, Enoxaparin Injury to the knee during six months prior to the experiment Expectations of surgical intervention, physiotherapy or other treatment of osteoarthritis before the end of the study period Significant irregularities in renal or liver function, active malignant disease in the last 3 years, heart failure, uncontrolled hypertension, active peptic ulcer, hematologic diseases, severe neurological diseases, and mental illness with seizures in the last two years. Peripheral neuropathy that treated by any drug High alcohol consumption (over 2 standard doses per day) Sensitivity to one of the ingredients and / or sensitivity to NSAIDs. It is Possible to include a patient who is sensitive to a specific drug from the family of NSAIDs, but can take other drugs from this family. Any medical condition or treatment which, in the opinion of the investigators, may mask the results of the study and / or interfere with the research questions and / or terminate the research properly and / or endanger the participant in any way during the course of the study.
Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The product in not drug or medical device (but a dietary supplement). There are 76 participants divided inti 2 groups : experimental group (38) and Placebo group (38). The period of the intervention: 90 days
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Solgar No7<br>Aflapin 100 mg and Collagen UC2 40 mg by mouth every 24 hours for 90 days | Dietary Supplement: Solgar No7 Complex<br>* Solgar No7 Capsules<br>|
| Placebo Comparator: Placebo for Solgar No7<br>Placebo 1 Capsule by mouth, every 24 hours for 90 days | Dietary Supplement: placebo<br>* Placebo tablets Cellulose<br>* Other names: Placebo for Solgar No7;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity | Self reported pain intensity in the scale 1-10 | Pain intensity Reported to the Doctor after one month of the treatment. Each item is scored 0-10 (0=no pain; 10=pain as bad as can be), yielding a total between 0 and 30. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee Stiffness | The stiffness of the knee according to the doctor evaluation | nee Stiffness checked by the Doctor after one month of treatment. Each item is scored 0-10 (0=no pain; 10=pain as bad as can be), yielding a total between 0 and 30 |
| Non Steroidal Anti Inflammatory Drugs Usage | Self reported Non Steroidal Anti Inflammatory Drugs Usage | Pain Medication Usage as Reported to the Doctor after one month of treatment. Each item is scored as a number of the dose units that were used during the all period (0=no medications, 1=only one dose of medication etc) |
| Adverse Reactions | Self reported Adverse Reactions | Adverse Reactions as Reported to the Doctor over the period of the treatment. Each item is scored as a number of the dose units that were used during the all period (0=no adverse reactions, 1=only one adverse reaction etc) |
|
|
NCT00160446
|
A Study to Evaluate the Safety and Effectiveness of Three Asoprisnil Doses in the Treatment of Women With Endometriosis
|
The objective of this study is to determine the safety and effectiveness of three doses of asoprisnil, compared to placebo, in the treatment of women with endometriosis.
|
Endometriosis, the presence of endometrial tissue outside the uterus, is a progressive, estrogen-dependent disease that occurs in menstruating women of reproductive age. Although all major endometriosis therapies are effective for the treatment of pain, no single treatment is superior to others in terms of efficacy. The major drawbacks of the current medical therapies are severe side effects such as hot flushes and osteoporosis. The objective of this study is to determine the safety and efficacy of asoprisnil 5, 10, and 25 mg tablets, compared to placebo, administered daily for 12 weeks to women with endometriosis, by assessing whether asoprisnil administration diminishes the pelvic pain, dysmenorrhea, dyspareunia, excessive bleeding, and analgesic use associated with this disease and lessens the subjects' perceived pain symptoms. Otherwise healthy women with surgically confirmed endometriosis will be enrolled.
|
A Phase II Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of J867 Administered in Patients With Endometriosis
|
Endometriosis
|
* Drug: Asoprisnil
* Drug: Asoprisnil
* Drug: Asoprisnil
* Drug: Placebo
|
Inclusion Criteria:~Surgically confirmed endometriosis~History of menstrual cycles between 26 and 32 days~Otherwise in good health~Age 18-40 years, inclusive~Subject had pain graded at Screening and Day 1 according to a scale suggested by Biberoglu and Berhman5 in at least one of the following categories:~moderate or severe pelvic pain not related to menstruation, OR~moderate or severe dysmenorrhea, OR~moderate or severe pelvic tenderness elicited on pelvic examination accompanied by non-menstrual pelvic pain.~Subject agrees to double barrier method of contraception~Exclusion Criteria:~Any abnormal lab or procedure result the study-doctor considers important~History of undiagnosed uterine bleeding or gynecological disorder~Severe reaction(s) to hormone therapy~History of osteoporosis or other metabolic bone disease~Subject currently breast feeding
|
18 Years
|
40 Years
|
Female
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain (dysmenorrhea, dyspareunia, pelvic pain) measured by daily diary | | Mean change from baseline to Months 1, 2, 3 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global efficacy question | | Final visit |
| Pain (dysmenorrhea, dyspareunia, pelvic pain) pelvic tenderness and induration evaluated during office visits using modified Biberoglu and Behrman grading scale | | Each monthly visit |
|
Pelvic pain, Dysmenorrhea, Dyspareunia, Infertility, Asoprisnil
|
Endometriosis, Genital Diseases, Female, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Genital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Asoprisnil<br>* 5mg Tablet, oral Daily for 12 weeks<br>|
| Experimental: 2<br> | Drug: Asoprisnil<br>* 10 mg Tablet, oral Daily for 12 weeks<br>|
| Experimental: 3<br> | Drug: Asoprisnil<br>* 25 mg Tablet, oral Daily for 12 weeks<br>|
| Placebo Comparator: 4<br> | Drug: Placebo<br>* Tablet, oral Daily for 12 weeks<br>|
|
A Study to Evaluate the Safety and Effectiveness of Three Asoprisnil Doses in the Treatment of Women With Endometriosis
Study Overview
=================
Brief Summary
-----------------
The objective of this study is to determine the safety and effectiveness of three doses of asoprisnil, compared to placebo, in the treatment of women with endometriosis.
Detailed Description
-----------------
Endometriosis, the presence of endometrial tissue outside the uterus, is a progressive, estrogen-dependent disease that occurs in menstruating women of reproductive age. Although all major endometriosis therapies are effective for the treatment of pain, no single treatment is superior to others in terms of efficacy. The major drawbacks of the current medical therapies are severe side effects such as hot flushes and osteoporosis. The objective of this study is to determine the safety and efficacy of asoprisnil 5, 10, and 25 mg tablets, compared to placebo, administered daily for 12 weeks to women with endometriosis, by assessing whether asoprisnil administration diminishes the pelvic pain, dysmenorrhea, dyspareunia, excessive bleeding, and analgesic use associated with this disease and lessens the subjects' perceived pain symptoms. Otherwise healthy women with surgically confirmed endometriosis will be enrolled.
Official Title
-----------------
A Phase II Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of J867 Administered in Patients With Endometriosis
Conditions
-----------------
Endometriosis
Intervention / Treatment
-----------------
* Drug: Asoprisnil
* Drug: Asoprisnil
* Drug: Asoprisnil
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Surgically confirmed endometriosis History of menstrual cycles between 26 and 32 days Otherwise in good health Age 18-40 years, inclusive Subject had pain graded at Screening and Day 1 according to a scale suggested by Biberoglu and Berhman5 in at least one of the following categories: moderate or severe pelvic pain not related to menstruation, OR moderate or severe dysmenorrhea, OR moderate or severe pelvic tenderness elicited on pelvic examination accompanied by non-menstrual pelvic pain. Subject agrees to double barrier method of contraception Exclusion Criteria: Any abnormal lab or procedure result the study-doctor considers important History of undiagnosed uterine bleeding or gynecological disorder Severe reaction(s) to hormone therapy History of osteoporosis or other metabolic bone disease Subject currently breast feeding
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Asoprisnil<br>* 5mg Tablet, oral Daily for 12 weeks<br>|
| Experimental: 2<br> | Drug: Asoprisnil<br>* 10 mg Tablet, oral Daily for 12 weeks<br>|
| Experimental: 3<br> | Drug: Asoprisnil<br>* 25 mg Tablet, oral Daily for 12 weeks<br>|
| Placebo Comparator: 4<br> | Drug: Placebo<br>* Tablet, oral Daily for 12 weeks<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain (dysmenorrhea, dyspareunia, pelvic pain) measured by daily diary | | Mean change from baseline to Months 1, 2, 3 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global efficacy question | | Final visit |
| Pain (dysmenorrhea, dyspareunia, pelvic pain) pelvic tenderness and induration evaluated during office visits using modified Biberoglu and Behrman grading scale | | Each monthly visit |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pelvic pain, Dysmenorrhea, Dyspareunia, Infertility, Asoprisnil
|
NCT00235898
|
Clinical Trial in Patients With Metastatic Colorectal Cancer
|
The objective of this trial is to compare efficacy and safety of CoFactor and 5-fluorouracil (5-FU) versus leucovorin and 5-FU in treatment of metastatic colorectal cancer.
|
A Multi-Center, Open Label, Parallel Group, Randomised, Phase IIB Clinical Trial to Evaluate the Safety and Efficacy of CoFactor and 5-FU Versus Leucovorin and 5-FU in Subjects With Metastatic Colorectal Carcinoma
|
Colon Cancer, Rectal Cancer
|
* Drug: CoFactor
* Drug: 5-FU
* Drug: Leucovorin
|
Inclusion Criteria:~Have surgically incurable, confirmed metastatic colon or rectal adenocarcinoma.~Be male or non-pregnant, non-lactating female subjects ≥ 18 years of age.~If female, and of childbearing potential, agree to use adequate contraception (as deemed by the investigator) throughout their participation in this study and for 30 days after discontinuation of study medication.~If, female of childbearing potential, have a negative pregnancy test prior to the start of the study.~Have a life expectancy of at least 6 months.~Have radiologically or clinically measurable disease for response assessment. Presence of ascites or pleural effusion(s) are not acceptable as single sites of response assessment, but may be present if dimensional or other discrete measurable disease is present for evaluation.~Have an ECOG Performance Level of 0-2 (or Karnofsky of 100-70). A lower ECOG or Karnofsky is acceptable only if clearly due to non-oncologic conditions (e.g., prior paraplegia from polio).~Have had no prior chemotherapy for established, metastatic disease. (Subjects may have received adjuvant chemotherapy with fluoropyrimidine therapy).~Have at least 6 months elapsed since prior adjuvant 5-FU or CPT-11 therapy, or Mitomycin C or nitrosourea therapy.~Have had at least an 8 week interval since any prior radiation therapy or 4 weeks since any major surgery.~Have recovered from any toxicities resulting from prior therapies (except for alopecia).~Adequate renal, bone marrow, liver function defined as serum creatinine less than 1.5 times the upper limit of normal, serum bilirubin less than 2 times the upper limit of normal, ANC greater than 1.5 x 109/L, Platelet count greater than 90 x 109/L, SGOT (AST) and SGPT (ALT) less than 3 times the upper limit of normal.~Exclusion Criteria:~Failure by the subject or the subject's legal representative to sign the Informed Consent.~An inability to obtain Informed Consent because of psychiatric or complex medical problems.~Have concurrent infection including diagnoses of FUO or evidence of possible central line sepsis (subjects must be afebrile at the start of therapy).~Have unstable oncologic emergency syndromes: superior vena cava (SVC) syndrome, rising bilirubin needing stent placement, spinal cord compression, progressive brain metastases, active bleeding, hypercalcemia, etc.~Have unstable medical conditions such as acute coronary syndrome, cardio-vascular accident within the previous 12 months (such as transient ischemic attacks, accelerated hypertension), etc.~Have cerebellar neurologic syndromes such as Parkinson's disease, multiple sclerosis, and amyotonia.~Have a known intolerance to fluoropyrimidine (5-FU, Capecitabine, Floxuridine, UFT) therapy (dihydropyrimidine dehydrogenase deficiency).~Patients with vomiting, diarrhea, or nausea of grade greater than 1.~Received any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment with study drug.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Leucovorin, Fluorouracil, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Antimetabolites, Antineoplastic, Antineoplastic Agents, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs, Antidotes, Protective Agents, Vitamin B Complex, Vitamins, Micronutrients
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>CoFactor, 5-FU | Drug: CoFactor<br> <br> * Other names: ANX-510;Drug: 5-FU<br> <br> * Other names: 5-Fluorouracil;|
| Active Comparator: 2<br>Leucovorin, 5-FU | Drug: 5-FU<br> <br> * Other names: 5-Fluorouracil;Drug: Leucovorin<br> <br> |
|
Clinical Trial in Patients With Metastatic Colorectal Cancer
Study Overview
=================
Brief Summary
-----------------
The objective of this trial is to compare efficacy and safety of CoFactor and 5-fluorouracil (5-FU) versus leucovorin and 5-FU in treatment of metastatic colorectal cancer.
Official Title
-----------------
A Multi-Center, Open Label, Parallel Group, Randomised, Phase IIB Clinical Trial to Evaluate the Safety and Efficacy of CoFactor and 5-FU Versus Leucovorin and 5-FU in Subjects With Metastatic Colorectal Carcinoma
Conditions
-----------------
Colon Cancer, Rectal Cancer
Intervention / Treatment
-----------------
* Drug: CoFactor
* Drug: 5-FU
* Drug: Leucovorin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have surgically incurable, confirmed metastatic colon or rectal adenocarcinoma. Be male or non-pregnant, non-lactating female subjects ≥ 18 years of age. If female, and of childbearing potential, agree to use adequate contraception (as deemed by the investigator) throughout their participation in this study and for 30 days after discontinuation of study medication. If, female of childbearing potential, have a negative pregnancy test prior to the start of the study. Have a life expectancy of at least 6 months. Have radiologically or clinically measurable disease for response assessment. Presence of ascites or pleural effusion(s) are not acceptable as single sites of response assessment, but may be present if dimensional or other discrete measurable disease is present for evaluation. Have an ECOG Performance Level of 0-2 (or Karnofsky of 100-70). A lower ECOG or Karnofsky is acceptable only if clearly due to non-oncologic conditions (e.g., prior paraplegia from polio). Have had no prior chemotherapy for established, metastatic disease. (Subjects may have received adjuvant chemotherapy with fluoropyrimidine therapy). Have at least 6 months elapsed since prior adjuvant 5-FU or CPT-11 therapy, or Mitomycin C or nitrosourea therapy. Have had at least an 8 week interval since any prior radiation therapy or 4 weeks since any major surgery. Have recovered from any toxicities resulting from prior therapies (except for alopecia). Adequate renal, bone marrow, liver function defined as serum creatinine less than 1.5 times the upper limit of normal, serum bilirubin less than 2 times the upper limit of normal, ANC greater than 1.5 x 109/L, Platelet count greater than 90 x 109/L, SGOT (AST) and SGPT (ALT) less than 3 times the upper limit of normal. Exclusion Criteria: Failure by the subject or the subject's legal representative to sign the Informed Consent. An inability to obtain Informed Consent because of psychiatric or complex medical problems. Have concurrent infection including diagnoses of FUO or evidence of possible central line sepsis (subjects must be afebrile at the start of therapy). Have unstable oncologic emergency syndromes: superior vena cava (SVC) syndrome, rising bilirubin needing stent placement, spinal cord compression, progressive brain metastases, active bleeding, hypercalcemia, etc. Have unstable medical conditions such as acute coronary syndrome, cardio-vascular accident within the previous 12 months (such as transient ischemic attacks, accelerated hypertension), etc. Have cerebellar neurologic syndromes such as Parkinson's disease, multiple sclerosis, and amyotonia. Have a known intolerance to fluoropyrimidine (5-FU, Capecitabine, Floxuridine, UFT) therapy (dihydropyrimidine dehydrogenase deficiency). Patients with vomiting, diarrhea, or nausea of grade greater than 1. Received any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment with study drug.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>CoFactor, 5-FU | Drug: CoFactor<br> <br> * Other names: ANX-510;Drug: 5-FU<br> <br> * Other names: 5-Fluorouracil;|
| Active Comparator: 2<br>Leucovorin, 5-FU | Drug: 5-FU<br> <br> * Other names: 5-Fluorouracil;Drug: Leucovorin<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
|||
NCT04597476
|
A Randomized, Double-blind Study to Evaluate the Clinical Effect and Safety of Fucoidan in Patients With Squamous Cell Carcinomas of the Head and Neck
|
This phase II study is a randomized, double-blind study that seeks to evaluate the clinical effects and safety of fucoidan in the treatment of cancer patients with stage III/IV head and neck squamous cell carcinoma.~Patients will be centrally randomized in a 1:1 ratio to receive either Fucoidan or placebo (potato starch) Eligible subjects will receive fucoidan twice daily (BID) in combination with chemotherapy and radiation therapy over a 24-week treatment period.~Clinical effects and safety parameters for all subjects who complete the treatment period will be followed for an additional 72 weeks after the treatment period.
|
This phase II study is a randomized, double-blind study that seeks to evaluate the clinical effects and safety of fucoidan in the treatment of cancer patients with stage III/IV head and neck squamous cell carcinoma.~Patients will be centrally randomized in a 1:1 ratio to receive either Fucoidan or placebo (potato starch) Eligible subjects will receive fucoidan twice daily (BID) in combination with chemotherapy and radiation therapy over a 24-week treatment period.~Clinical effects and safety parameters for all subjects who complete the treatment period will be followed for an additional 72 weeks after the treatment period.~The total length of the study for each subject will be approximately 100 weeks, comprising the following time periods: screening period (28 days), treatment period (24 weeks), and follow-up period (72 weeks).
|
A Randomized, Double-blind Study to Evaluate the Clinical Effect and Safety of Fucoidan in Patients With Squamous Cell Carcinomas of the Head and Neck
|
Squamous Cell Carcinomas of the Head and Neck
|
* Dietary Supplement: Fucoidan
* Other: Placebo( Potato starch)
|
Inclusion Criteria:~The patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) withoutdistant metastasis who had not received any treatment to head and neck cancer can be enrolled in this study.~Completed a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the head and neck (including the primary tumor and neck nodes) within 6 weeks prior to enrollment.~Adequate renal function, with serum creatinine ≤ 1.5 mg/dL. Patients with serum creatinine > 1.5 mg/dL may be eligible if calculated creatinine clearance ≥ 55 mL/min as based on the results of the Cockcroft-Gault Equation or 24-hour urine collection.~Age ≥ 20 years and ≤ 75 years.~Eastern Cooperative Oncology Group (ECOG) Performance Status = 0-1.~Expected lifespan > 6 months.~Adequate bone marrow function, as defined by absolute neutrophil count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL.~Adequate hepatic function, with total bilirubin ≤ 1.5 × upper normal limit (UNL; patients with hyperbilirubinemia caused by Gilbert's syndrome may be eligible if total bilirubin ≤ 2.5 × UNL), aspartate aminotransferase (AST) ≤ 2.5 × UNL, alanine aminotransferase (ALT) ≤ 2.5 × UNL, and alkaline phosphatase (ALP) ≤ 2.5 × UNL.~Men and women of childbearing potential must consent to the use of effective contraception while on treatment period.~Patients must be able to understand and be willing to sign a written informed consent document.~Patients must be able to comply with the study protocol.~Exclusion Criteria:~Diagnosed as nasopharyngeal cancer.~Body mass index (BMI) < 18.5.~Significant history of cardiac disease (i.e. uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias, etc.).~Patients with a history of any other malignancy (except squamous or basal cell skin cancer or cervical carcinoma in situ) are ineligible, unless the patient has been continuously disease-free for at least 5 years.~Previously received chemotherapy, radiation therapy, or immunotherapy for head and neck cancer.~Dysphagia patients who do not consent to nasogastric (NG), orogastric (OG), or percutaneous endoscopic gastrostomy (PEG) feeding.~History or clinical evidence of any hyperthyroidism, cirrhosis, hepatic failure, human immunodeficiency virus (HIV) infection, renal failure (as determined by a serum creatinine > 250 µmol/L or > 2.83 mg/dL at screening), active tuberculosis (as confirmed by sputum or other microbiological methods within the last five years), or active hepatitis B/C.~Any other clinical disorders or unsuitable conditions that render the patient ineligible for this study, as determined by the principal investigator(s).~Treatment with any investigational product or health supplement within 28 days prior to enrollment.~Pregnant or breastfeeding women.~Non-compliance with the requirement for contraception or other aspects of the study protocol.~Inability to understand and provide informed consent regarding participation in this study.
|
20 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Fucoidan Group: Fucoidan 4.4 g, PO, bid for 24 weeks Placebo Group: Potato starch 4.4 g, PO, bid for 24 weeks
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate disease-free survival (DFS) of patients treated with a combination of fucoidan, chemotherapy, and radiation therapy | To evaluate disease-free survival (DFS) of patients treated with a combination of fucoidan, chemotherapy, and radiation therapy | From date of randomization and assessed up to 96 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate pain in patients treated with a combination of fucoidan, chemotherapy, and radiation therapy | To evaluate pain in patients treated with a combination of fucoidan, chemotherapy, and radiation therapy by a numerical rating scale (NRS: 0-10) | From date of randomization to the end of treatment period, up to 24 weeks |
| To evaluate the disease control rate (DCR) of patients treated with a combination of fucoidan, chemotherapy, and radiation therapy | To evaluate the disease control rate (DCR) of patients treated with a combination of fucoidan, chemotherapy, and radiation therapy | From date of randomization and assessed up to 96 weeks |
|
Fucoidan, Anti-Ulcer Agents, Gastrointestinal Agents, Anticoagulants, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fucoidan Group<br>Fucoidan powder at 4.4 g per sachet (dose) for oral administration. Fucoidan 4.4 g, PO, bid for 24 weeks | Dietary Supplement: Fucoidan<br>* Fucoidan refers to a class of fucose-enriched sulfated polysaccharides with an average molecular weight of 20,000 Daltons (Da), which can be found in many varieties of edible brown seaweeds and algae . In cell culture studies and animal studies, fucoidan has been shown to possess a range of biological activities, including anti-cancer, anti-inflammatory, and immunoregulatory effects . A recent in vitro study conducted in head and neck squamous cell carcinoma (HNSCC) cell lines (H103, FaDu, and KB) showed that fucoidan could induce cell cycle arrest and possibly apoptosis in a dose-dependent manner, while also enhancing response to cisplatin treatment . In addition, fucoidan has also been shown to inhibit the proliferation of nasopharyngeal carcinoma cells and MC3 human mucoepidermoid carcinoma (MEC) cells .<br>|
| Placebo Comparator: Potato starch<br>Potato starch at 4.4 g per sachet (dose) for oral administration. Potato starch 4.4 g, PO, bid for 24 weeks | Other: Placebo( Potato starch)<br>* Potato starch 4.4gram<br>|
|
A Randomized, Double-blind Study to Evaluate the Clinical Effect and Safety of Fucoidan in Patients With Squamous Cell Carcinomas of the Head and Neck
Study Overview
=================
Brief Summary
-----------------
This phase II study is a randomized, double-blind study that seeks to evaluate the clinical effects and safety of fucoidan in the treatment of cancer patients with stage III/IV head and neck squamous cell carcinoma. Patients will be centrally randomized in a 1:1 ratio to receive either Fucoidan or placebo (potato starch) Eligible subjects will receive fucoidan twice daily (BID) in combination with chemotherapy and radiation therapy over a 24-week treatment period. Clinical effects and safety parameters for all subjects who complete the treatment period will be followed for an additional 72 weeks after the treatment period.
Detailed Description
-----------------
This phase II study is a randomized, double-blind study that seeks to evaluate the clinical effects and safety of fucoidan in the treatment of cancer patients with stage III/IV head and neck squamous cell carcinoma. Patients will be centrally randomized in a 1:1 ratio to receive either Fucoidan or placebo (potato starch) Eligible subjects will receive fucoidan twice daily (BID) in combination with chemotherapy and radiation therapy over a 24-week treatment period. Clinical effects and safety parameters for all subjects who complete the treatment period will be followed for an additional 72 weeks after the treatment period. The total length of the study for each subject will be approximately 100 weeks, comprising the following time periods: screening period (28 days), treatment period (24 weeks), and follow-up period (72 weeks).
Official Title
-----------------
A Randomized, Double-blind Study to Evaluate the Clinical Effect and Safety of Fucoidan in Patients With Squamous Cell Carcinomas of the Head and Neck
Conditions
-----------------
Squamous Cell Carcinomas of the Head and Neck
Intervention / Treatment
-----------------
* Dietary Supplement: Fucoidan
* Other: Placebo( Potato starch)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) withoutdistant metastasis who had not received any treatment to head and neck cancer can be enrolled in this study. Completed a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the head and neck (including the primary tumor and neck nodes) within 6 weeks prior to enrollment. Adequate renal function, with serum creatinine ≤ 1.5 mg/dL. Patients with serum creatinine > 1.5 mg/dL may be eligible if calculated creatinine clearance ≥ 55 mL/min as based on the results of the Cockcroft-Gault Equation or 24-hour urine collection. Age ≥ 20 years and ≤ 75 years. Eastern Cooperative Oncology Group (ECOG) Performance Status = 0-1. Expected lifespan > 6 months. Adequate bone marrow function, as defined by absolute neutrophil count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL. Adequate hepatic function, with total bilirubin ≤ 1.5 × upper normal limit (UNL; patients with hyperbilirubinemia caused by Gilbert's syndrome may be eligible if total bilirubin ≤ 2.5 × UNL), aspartate aminotransferase (AST) ≤ 2.5 × UNL, alanine aminotransferase (ALT) ≤ 2.5 × UNL, and alkaline phosphatase (ALP) ≤ 2.5 × UNL. Men and women of childbearing potential must consent to the use of effective contraception while on treatment period. Patients must be able to understand and be willing to sign a written informed consent document. Patients must be able to comply with the study protocol. Exclusion Criteria: Diagnosed as nasopharyngeal cancer. Body mass index (BMI) < 18.5. Significant history of cardiac disease (i.e. uncontrolled hypertension, unstable angina, congestive heart failure, or uncontrolled arrhythmias, etc.). Patients with a history of any other malignancy (except squamous or basal cell skin cancer or cervical carcinoma in situ) are ineligible, unless the patient has been continuously disease-free for at least 5 years. Previously received chemotherapy, radiation therapy, or immunotherapy for head and neck cancer. Dysphagia patients who do not consent to nasogastric (NG), orogastric (OG), or percutaneous endoscopic gastrostomy (PEG) feeding. History or clinical evidence of any hyperthyroidism, cirrhosis, hepatic failure, human immunodeficiency virus (HIV) infection, renal failure (as determined by a serum creatinine > 250 µmol/L or > 2.83 mg/dL at screening), active tuberculosis (as confirmed by sputum or other microbiological methods within the last five years), or active hepatitis B/C. Any other clinical disorders or unsuitable conditions that render the patient ineligible for this study, as determined by the principal investigator(s). Treatment with any investigational product or health supplement within 28 days prior to enrollment. Pregnant or breastfeeding women. Non-compliance with the requirement for contraception or other aspects of the study protocol. Inability to understand and provide informed consent regarding participation in this study.
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Fucoidan Group: Fucoidan 4.4 g, PO, bid for 24 weeks Placebo Group: Potato starch 4.4 g, PO, bid for 24 weeks
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fucoidan Group<br>Fucoidan powder at 4.4 g per sachet (dose) for oral administration. Fucoidan 4.4 g, PO, bid for 24 weeks | Dietary Supplement: Fucoidan<br>* Fucoidan refers to a class of fucose-enriched sulfated polysaccharides with an average molecular weight of 20,000 Daltons (Da), which can be found in many varieties of edible brown seaweeds and algae . In cell culture studies and animal studies, fucoidan has been shown to possess a range of biological activities, including anti-cancer, anti-inflammatory, and immunoregulatory effects . A recent in vitro study conducted in head and neck squamous cell carcinoma (HNSCC) cell lines (H103, FaDu, and KB) showed that fucoidan could induce cell cycle arrest and possibly apoptosis in a dose-dependent manner, while also enhancing response to cisplatin treatment . In addition, fucoidan has also been shown to inhibit the proliferation of nasopharyngeal carcinoma cells and MC3 human mucoepidermoid carcinoma (MEC) cells .<br>|
| Placebo Comparator: Potato starch<br>Potato starch at 4.4 g per sachet (dose) for oral administration. Potato starch 4.4 g, PO, bid for 24 weeks | Other: Placebo( Potato starch)<br>* Potato starch 4.4gram<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate disease-free survival (DFS) of patients treated with a combination of fucoidan, chemotherapy, and radiation therapy | To evaluate disease-free survival (DFS) of patients treated with a combination of fucoidan, chemotherapy, and radiation therapy | From date of randomization and assessed up to 96 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate pain in patients treated with a combination of fucoidan, chemotherapy, and radiation therapy | To evaluate pain in patients treated with a combination of fucoidan, chemotherapy, and radiation therapy by a numerical rating scale (NRS: 0-10) | From date of randomization to the end of treatment period, up to 24 weeks |
| To evaluate the disease control rate (DCR) of patients treated with a combination of fucoidan, chemotherapy, and radiation therapy | To evaluate the disease control rate (DCR) of patients treated with a combination of fucoidan, chemotherapy, and radiation therapy | From date of randomization and assessed up to 96 weeks |
|
|
NCT03649165
|
A Study to Evaluate Bioavailability and Food Effect of Selumetinib (AZD6244) in Healthy Male Participants
|
This study will evaluate bioavailability and food effect of selumetinib (AZD6244) in healthy male participants. A total of 24 healthy male participants will be included to ensure at least 20 evaluable participants. The study is divided in 2 study parts; the same participants will participate in both parts of the study. Part 1 of the study is to investigate the pharmacokinetics (PK) of the selumetinib granule compared to the PK of selumetinib capsule, when administered with water under the fasted conditions. Part 2 of the study is to investigate the PK of selumetinib granule and capsule under fed conditions. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration.
|
This study will be a 2-part, open-label, single-center relative bioavailability and food effect randomized crossover study of new granule and capsule formulations of selumetinib. A total of 24 healthy male participants aged between 18 to 45 years (inclusive), will be included to ensure at least 20 evaluable participants. The study is divided in 2 study parts; the same participants will participate in both parts of the study.~Part 1 of the study is designed to investigate the PK of the selumetinib granule compared to the PK of selumetinib capsule, when administered with water under the fasted conditions. Part 2 of the study is designed to investigate the PK of selumetinib granule and capsule under fed conditions. Participants will consume a low-fat, low-calorie meal. Thirty minutes after the start of the meal, selumetinib will be administered to the participants. In all treatment periods, participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration where it will act as a marker for gastric emptying. The study will also assess the palatability of the selumetinib granule in both parts of the study.~Each participant will receive the following treatments:~Treatment A: 25 mg granule, fasted state~Treatment B: 50 mg capsule, fasted state~Treatment C: 25 mg granule, fed state~Treatment D: 50 mg capsule, fed state Participant will be randomly assigned to 1 of 4 treatment sequences. In all cases the treatments in Part 1 will be administered before the treatments in Part 2. The study will comprise of a screening period of maximum 28 days. Four treatment periods during which participants will be resident from the day before dosing (Day -1) until at least 48 hours after dosing; discharged on the morning of Day 3. A follow-up visit, will be within 7 to 10 days after the last dose of investigational medicinal product (IMP). There will be a minimum washout period of at least 5 days between each IMP administration. Each participant will be involved in the study for approximately 8 to 9 weeks.
|
A Phase I, Open-label, Single-center Relative Bioavailability and Food Effect Randomized Crossover Study of New Granule and Capsule Formulations of Selumetinib (AZD6244) in Healthy Male Subjects
|
Neurofibromatosis Type 1 (NF1)-Related Plexiform Neurofibromas (PNs), Healthy Participants
|
* Drug: Treatment A
* Drug: Treatment B
* Drug: Treatment C
* Drug: Treatment D
* Drug: Acetaminophen
|
Inclusion Criteria~Provision of signed and dated, written informed consent before any study-specific procedures.~Healthy male participants aged 18 to 45 years (inclusive) with suitable veins for cannulation or repeated venipuncture.~Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg.~Participants is able to consume a low-fat meal within a 30-minute period.~Participants has a creatinine clearance (CRCL) greater than 50 mL/min using Cockcroft-Gault formula.~Participants is willing to comply with contraception requirements as described below:~Male participants with sexual partners who can become pregnant (i.e., women of childbearing potential) must use 2 highly-effective methods of contraception, one of which must be a barrier method (condom with spermicide) from the time of the first administration of the IMP until 12 weeks after the last administration of the IMP to avoid pregnancy and/or potential adverse effects on the developing embryo.~Participants with sexual partners who are pregnant must use an effective method of contraception (barrier method) from the time of the first administration of the IMP until 12 weeks after the last administration of the IMP.~Participants must avoid sperm donation during the study and for 12 weeks after the last administration of the IMP.~Reliable methods of contraception must be used consistently and correctly.~Reliable methods of contraception for participants include: Use of barrier methods (condom and spermicide) for the duration of the study until 12 weeks after the last administration of the IMP.~Acceptable methods for participants partners include:~Use of implants, injectables and combined oral contraceptives (must be used in combination with a barrier method of contraception)~Use of intrauterine devices (must be used in combination with a barrier method of contraception)~Exclusion Criteria :~Participants of Japanese, non-Japanese Asian or Indian ethnicity.~Participants has any one parent or grandparent (maternal or paternal) that was Japanese or non-Japanese Asian (e.g., China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia) or Indian.~History or presence of central serous retinopathy or retinal vein thrombosis, IOP greater than 21 mmHg or uncontrolled glaucoma.~History of any clinically significant disease or disorder which, in the opinion of the PI, may put the participant at risk because of participation in the study, influence the result of the study or influence the participants ability to participate in the study.~Participant has ophthalmologic conditions as follows:~Current or past history of central serous retinopathy/retinal pigment epithelial detachment or retinal vein occlusion.~Intra-ocular pressure > 21 mmHg or uncontrolled glaucoma (irrespective of IOP).~Participant has any cardiac conditions as follows:~Uncontrolled hypertension (BP ≥ 150/95 mmHg despite medical therapy).~Acute coronary syndrome within 6 months before starting treatment.~Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy.~Symptomatic heart failure New York Heart Association (NYHA) Class II-IV, prior or current cardiomyopathy, or severe valvular heart disease.~Prior or current cardiomyopathy including but not limited to the following: 1) Known hypertrophic cardiomyopathy.~2) Known arrhythmogenic right ventricular cardiomyopathy. 3) Previous moderate or severe impairment of LVEF < 45% on echocardiography even if full recovery has occurred.~Left ventricular ejection fraction below the lower limit of normal (LLN) or < 55% measured by ECHO at the Screening Visit.~Severe valvular heart disease.~Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on ECG at rest.~QTcF > 450 ms or other factors that increase the risk of QT prolongation.~Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.~Any clinically relevant abnormal findings in physical examination, hematology, clinical chemistry, urinalysis, vital signs or ECG at the Screening Visit, which in the opinion of the PI, may put the participant at risk because of his participation in the study. Test may be repeated twice at the discretion of the Investigator if abnormal.~Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.~A suspected/manifested infection according to the International Air Transport Association (IATA) Categories A and B infectious substances.~History of, or current alcohol or drug abuse, as judged by the principal investigator (PI).~Participation in another clinical study (investigational product administered within 30 days before the Screening Visit, or participation in a method development study [no drug] 30 days before the Screening Visit). Participation is defined as the completion of a treatment related visit.~Planned in-patient surgery, dental procedure or hospitalization during the study.~Plasma donation within 30 days of the Screening Visit or any blood donation/loss more than 500 mL during the 90 days before the Screening Visit.~A definite or suspected personal history of intolerance or hypersensitivity to drugs and/or their excipients, judged to be clinically relevant by the PI.~Known severe hypersensitivity to selumetinib or acetaminophen or any excipient of these medicinal products or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib.~Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 90 days before the Screening Visit.~Positive screen for drugs of abuse, alcohol or cotinine at the Screening Visit or on each admission to the Clinical Unit or positive screen for alcohol on each admission to the Clinical Unit.~Use of drugs with enzyme-inducing properties such as St John's Wort within 4 weeks before the first administration of IMP.~Use of any prescribed medicine and over-the-counter (OTC) drugs (including herbal remedies, vitamins and minerals) within 2 weeks or 5 times the half-life, whichever is the longer, of the respective drug before Day -1 or Treatment Period 1. No medications known to prolong the QT/QTc interval are allowed.~Excessive intake of caffeine-containing drinks or food e.g., coffee, tea, chocolate, Red Bull or cola (more than 6 units of caffeine per day). One caffeine unit is contained in the following items: 1 (6 oz) cup of coffee, 2 (12 oz) cans of cola, 1 (12 oz) cup of tea, ½ (4 oz) cup of energy drink (e.g., Red Bull) or 3 oz of chocolate.~Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI.~Involvement of any AstraZeneca, PAREXEL or Clinical Unit employee or their close relatives.~Participants who have previously been randomized to treatment in the current study.~Judgment by the PI that the participant should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.~Vulnerable participants , e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
|
18 Years
|
45 Years
|
Male
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Dose normalized area under plasma concentration-time curve from time zero to infinity (AUC/D) | To compare the AUC/D of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Dose normalized area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast/D) | To compare the AUClast/D of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Dose normalized maximum observed plasma concentration (Cmax/D) | To compare the Cmax/D of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Fraction of administered selumetinib granule dose systemically available relative to the capsule reference (Frel) | To compare the Frel. of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Area under plasma concentration time curve from time zero to infinity (AUC) | To compare AUC of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) | To compare AUClast of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Area under the plasma concentration-time curve from zero to 12 hours post-dose [AUC(0-12)] | To compare AUC (0-12) of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Maximum observed plasma concentration (Cmax) | To compare Cmax of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Ratio of AUC in fed state to AUC in the fasted state (FRAUC) | To compare FRAUC of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Ratio of Cmax in fed state to Cmax in the fasted state (FRCmax) | To compare FRCmax of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) | To compare t½λz of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Time to reach maximum observed plasma concentration (tmax) | To compare tmax of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Terminal elimination rate constant (λz) | To compare λz of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib plasma PK parameters: Apparent total body clearance of drug from plasma after extravascular administration (parent drug only) (CL/F) | To compare CL/F of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib plasma PK parameters: Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) | To compare Vz/F of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: AUC | To compare AUC of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: AUClast | To compare AUClast of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: AUC(0-12) | To compare AUC (0-12) of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Cmax | To compare Cmax of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: FRAUC | To compare FRAUC of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: FRCmax | To compare FRCmax of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: t½λz | To compare t½λz of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: tmax | To compare tmax of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: λz | To compare λz of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib plasma PK parameters: CL/F | To compare CL/F of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib plasma PK parameters: Vz/F | To compare Vz/F of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Taste questionnaire | To assess palatability of selumetinib granule formulation. The standardized questionnaire will be administered to participants within 10 minutes following intake of selumetinib granule. Questionnaire about taste include sweet, salty, sour, bitter, metallic, and hot/spicy. Where 0 indicates not at all and 10 indicates extremely. | At Days -1 to 3 (within 10 minutes following intake of selumetinib granule) |
| Number of participants with adverse events (AEs) | To assess the safety and tolerability of single doses of selumetinib in healthy participants. | From the time of informed consent, throughout the treatment periods up to and including the Follow-up Visit (7 to 10 days after last dose) |
| Vital signs (systolic blood pressure [BP]) | To assess systolic BP as a variable of safety and tolerability of single doses of selumetinib in healthy participants. Participants should be supine and at rest for at least 5 minutes before the measurements. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Vital signs (diastolic BP) | To assess diastolic BP as a variable of safety and tolerability of single doses of selumetinib in healthy participants. Participants should be supine and at rest for at least 5 minutes before the measurements. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Pulse rate | To assess pulse rate as a variable of safety and tolerability of single doses of selumetinib in healthy participants.~Participants should be supine and at rest for at least 5 minutes before the measurements. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| 12-lead electrocardiogram (ECG) | To assess 12-lead ECG as variable of safety and tolerability of single doses of selumetinib in healthy participants. Participants should be supine and at rest 10 minutes before recording the ECG. | From baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Number of participants with abnormal findings in physical examination | To assess physical examination as a variable safety and tolerability of single doses of selumetinib in healthy participants. | From baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Ophthalmic examinations | To assess ophthalmic examination as a variable of safety and tolerability of single doses of selumetinib in healthy participants. Ophthalmic examination included best corrected visual acuity, intra-ocular pressure and slit-lamp fundoscopy. | At screening Visit or on Day -1 of Treatment Period 1 |
| Laboratory assessments: hematology - Hemoglobin (Hb) | To assess Hb as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: hematology - erythrocyte count | To assess erythrocyte count as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: hematology: Platelet count | To assess platelet count as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: hematology: leucocyte differential count (absolute count) | To assess leucocyte differential count as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: hematology: leucocyte cell count | To assess leucocyte cell count as variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments:hematology - differential count | To assess differential count of neutrophils, lymphocytes, monocyets, eosinophils and basophils) as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry - electrolytes | To assess serum level of sodium, potassium, magnesium and phosphate as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry - urea nitrogen | To assess urea nitrogen as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry - creatinine | To assess creatinine as variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: albumin | To assess albumin as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: Total Calcium | To assess total calcium as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: Total protein | To assess total protein as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: Total bilirubin | To assess total bilirubin as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: Creatine phosphokinase (CPK) | To assess CPK as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: Troponin (isoform as per institutional norm) | To assess troponin as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry - Liver enzymes | To assess serum of Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Gamma glutamyl transpeptidase (GGT) as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Clinical urinalysis - glucose | To assess urine glucose as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Clinical Urinalysis - protein | To assess urine protein as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Clinical Urinalysis - blood | To assess urine blood as a variable of safety and tolerability of single doses of selumetinib in healthy participants.~If urinalysis is positive for blood, a microscopy test will be performed to assess RBC, white blood cell [WBC], casts [cellular, granular, hyaline]). | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
|
MEK Inhibitor, Selumetinib capsule, Selumetinib granule, PK, Bioavailibilty, Crossover study, Open-label, Food effect
|
Acetaminophen, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Antipyretics
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence 1<br>Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3, and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration where it will act as a marker for gastric emptying. | Drug: Treatment A<br>* During Part 1 of the study, participants will receive single doses of selumetinib 25 mg granule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment B<br>* During Part 1 of the study, participants will receive single doses of selumetinib 50 mg capsule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment C<br>* During Part 2 of the study, participants will receive single doses of selumetinib 25 mg granule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Treatment D<br>* During Part 2 of the study, participants will receive single doses of selumetinib 50 mg capsule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Acetaminophen<br>* Participants will receive a single 500mg dose of acetaminophen at the same time.<br>|
| Experimental: Treatment Sequence 2<br>Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3 and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration where it will act as a marker for gastric emptying. | Drug: Treatment A<br>* During Part 1 of the study, participants will receive single doses of selumetinib 25 mg granule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment B<br>* During Part 1 of the study, participants will receive single doses of selumetinib 50 mg capsule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment C<br>* During Part 2 of the study, participants will receive single doses of selumetinib 25 mg granule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Treatment D<br>* During Part 2 of the study, participants will receive single doses of selumetinib 50 mg capsule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Acetaminophen<br>* Participants will receive a single 500mg dose of acetaminophen at the same time.<br>|
| Experimental: Treatment Sequence 3<br>Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration where it will act as a marker for gastric emptying. | Drug: Treatment A<br>* During Part 1 of the study, participants will receive single doses of selumetinib 25 mg granule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment B<br>* During Part 1 of the study, participants will receive single doses of selumetinib 50 mg capsule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment C<br>* During Part 2 of the study, participants will receive single doses of selumetinib 25 mg granule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Treatment D<br>* During Part 2 of the study, participants will receive single doses of selumetinib 50 mg capsule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Acetaminophen<br>* Participants will receive a single 500mg dose of acetaminophen at the same time.<br>|
| Experimental: Treatment Sequence 4<br>Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration where it will act as a marker for gastric emptying. | Drug: Treatment A<br>* During Part 1 of the study, participants will receive single doses of selumetinib 25 mg granule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment B<br>* During Part 1 of the study, participants will receive single doses of selumetinib 50 mg capsule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment C<br>* During Part 2 of the study, participants will receive single doses of selumetinib 25 mg granule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Treatment D<br>* During Part 2 of the study, participants will receive single doses of selumetinib 50 mg capsule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Acetaminophen<br>* Participants will receive a single 500mg dose of acetaminophen at the same time.<br>|
|
A Study to Evaluate Bioavailability and Food Effect of Selumetinib (AZD6244) in Healthy Male Participants
Study Overview
=================
Brief Summary
-----------------
This study will evaluate bioavailability and food effect of selumetinib (AZD6244) in healthy male participants. A total of 24 healthy male participants will be included to ensure at least 20 evaluable participants. The study is divided in 2 study parts; the same participants will participate in both parts of the study. Part 1 of the study is to investigate the pharmacokinetics (PK) of the selumetinib granule compared to the PK of selumetinib capsule, when administered with water under the fasted conditions. Part 2 of the study is to investigate the PK of selumetinib granule and capsule under fed conditions. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration.
Detailed Description
-----------------
This study will be a 2-part, open-label, single-center relative bioavailability and food effect randomized crossover study of new granule and capsule formulations of selumetinib. A total of 24 healthy male participants aged between 18 to 45 years (inclusive), will be included to ensure at least 20 evaluable participants. The study is divided in 2 study parts; the same participants will participate in both parts of the study. Part 1 of the study is designed to investigate the PK of the selumetinib granule compared to the PK of selumetinib capsule, when administered with water under the fasted conditions. Part 2 of the study is designed to investigate the PK of selumetinib granule and capsule under fed conditions. Participants will consume a low-fat, low-calorie meal. Thirty minutes after the start of the meal, selumetinib will be administered to the participants. In all treatment periods, participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration where it will act as a marker for gastric emptying. The study will also assess the palatability of the selumetinib granule in both parts of the study. Each participant will receive the following treatments: Treatment A: 25 mg granule, fasted state Treatment B: 50 mg capsule, fasted state Treatment C: 25 mg granule, fed state Treatment D: 50 mg capsule, fed state Participant will be randomly assigned to 1 of 4 treatment sequences. In all cases the treatments in Part 1 will be administered before the treatments in Part 2. The study will comprise of a screening period of maximum 28 days. Four treatment periods during which participants will be resident from the day before dosing (Day -1) until at least 48 hours after dosing; discharged on the morning of Day 3. A follow-up visit, will be within 7 to 10 days after the last dose of investigational medicinal product (IMP). There will be a minimum washout period of at least 5 days between each IMP administration. Each participant will be involved in the study for approximately 8 to 9 weeks.
Official Title
-----------------
A Phase I, Open-label, Single-center Relative Bioavailability and Food Effect Randomized Crossover Study of New Granule and Capsule Formulations of Selumetinib (AZD6244) in Healthy Male Subjects
Conditions
-----------------
Neurofibromatosis Type 1 (NF1)-Related Plexiform Neurofibromas (PNs), Healthy Participants
Intervention / Treatment
-----------------
* Drug: Treatment A
* Drug: Treatment B
* Drug: Treatment C
* Drug: Treatment D
* Drug: Acetaminophen
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Provision of signed and dated, written informed consent before any study-specific procedures. Healthy male participants aged 18 to 45 years (inclusive) with suitable veins for cannulation or repeated venipuncture. Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg. Participants is able to consume a low-fat meal within a 30-minute period. Participants has a creatinine clearance (CRCL) greater than 50 mL/min using Cockcroft-Gault formula. Participants is willing to comply with contraception requirements as described below: Male participants with sexual partners who can become pregnant (i.e., women of childbearing potential) must use 2 highly-effective methods of contraception, one of which must be a barrier method (condom with spermicide) from the time of the first administration of the IMP until 12 weeks after the last administration of the IMP to avoid pregnancy and/or potential adverse effects on the developing embryo. Participants with sexual partners who are pregnant must use an effective method of contraception (barrier method) from the time of the first administration of the IMP until 12 weeks after the last administration of the IMP. Participants must avoid sperm donation during the study and for 12 weeks after the last administration of the IMP. Reliable methods of contraception must be used consistently and correctly. Reliable methods of contraception for participants include: Use of barrier methods (condom and spermicide) for the duration of the study until 12 weeks after the last administration of the IMP. Acceptable methods for participants partners include: Use of implants, injectables and combined oral contraceptives (must be used in combination with a barrier method of contraception) Use of intrauterine devices (must be used in combination with a barrier method of contraception) Exclusion Criteria : Participants of Japanese, non-Japanese Asian or Indian ethnicity. Participants has any one parent or grandparent (maternal or paternal) that was Japanese or non-Japanese Asian (e.g., China, Taiwan, Korea, Philippines, Thailand, Vietnam and Malaysia) or Indian. History or presence of central serous retinopathy or retinal vein thrombosis, IOP greater than 21 mmHg or uncontrolled glaucoma. History of any clinically significant disease or disorder which, in the opinion of the PI, may put the participant at risk because of participation in the study, influence the result of the study or influence the participants ability to participate in the study. Participant has ophthalmologic conditions as follows: Current or past history of central serous retinopathy/retinal pigment epithelial detachment or retinal vein occlusion. Intra-ocular pressure > 21 mmHg or uncontrolled glaucoma (irrespective of IOP). Participant has any cardiac conditions as follows: Uncontrolled hypertension (BP ≥ 150/95 mmHg despite medical therapy). Acute coronary syndrome within 6 months before starting treatment. Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy. Symptomatic heart failure New York Heart Association (NYHA) Class II-IV, prior or current cardiomyopathy, or severe valvular heart disease. Prior or current cardiomyopathy including but not limited to the following: 1) Known hypertrophic cardiomyopathy. 2) Known arrhythmogenic right ventricular cardiomyopathy. 3) Previous moderate or severe impairment of LVEF < 45% on echocardiography even if full recovery has occurred. Left ventricular ejection fraction below the lower limit of normal (LLN) or < 55% measured by ECHO at the Screening Visit. Severe valvular heart disease. Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on ECG at rest. QTcF > 450 ms or other factors that increase the risk of QT prolongation. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP. Any clinically relevant abnormal findings in physical examination, hematology, clinical chemistry, urinalysis, vital signs or ECG at the Screening Visit, which in the opinion of the PI, may put the participant at risk because of his participation in the study. Test may be repeated twice at the discretion of the Investigator if abnormal. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody. A suspected/manifested infection according to the International Air Transport Association (IATA) Categories A and B infectious substances. History of, or current alcohol or drug abuse, as judged by the principal investigator (PI). Participation in another clinical study (investigational product administered within 30 days before the Screening Visit, or participation in a method development study [no drug] 30 days before the Screening Visit). Participation is defined as the completion of a treatment related visit. Planned in-patient surgery, dental procedure or hospitalization during the study. Plasma donation within 30 days of the Screening Visit or any blood donation/loss more than 500 mL during the 90 days before the Screening Visit. A definite or suspected personal history of intolerance or hypersensitivity to drugs and/or their excipients, judged to be clinically relevant by the PI. Known severe hypersensitivity to selumetinib or acetaminophen or any excipient of these medicinal products or history of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 90 days before the Screening Visit. Positive screen for drugs of abuse, alcohol or cotinine at the Screening Visit or on each admission to the Clinical Unit or positive screen for alcohol on each admission to the Clinical Unit. Use of drugs with enzyme-inducing properties such as St John's Wort within 4 weeks before the first administration of IMP. Use of any prescribed medicine and over-the-counter (OTC) drugs (including herbal remedies, vitamins and minerals) within 2 weeks or 5 times the half-life, whichever is the longer, of the respective drug before Day -1 or Treatment Period 1. No medications known to prolong the QT/QTc interval are allowed. Excessive intake of caffeine-containing drinks or food e.g., coffee, tea, chocolate, Red Bull or cola (more than 6 units of caffeine per day). One caffeine unit is contained in the following items: 1 (6 oz) cup of coffee, 2 (12 oz) cans of cola, 1 (12 oz) cup of tea, ½ (4 oz) cup of energy drink (e.g., Red Bull) or 3 oz of chocolate. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI. Involvement of any AstraZeneca, PAREXEL or Clinical Unit employee or their close relatives. Participants who have previously been randomized to treatment in the current study. Judgment by the PI that the participant should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements. Vulnerable participants , e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence 1<br>Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3, and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration where it will act as a marker for gastric emptying. | Drug: Treatment A<br>* During Part 1 of the study, participants will receive single doses of selumetinib 25 mg granule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment B<br>* During Part 1 of the study, participants will receive single doses of selumetinib 50 mg capsule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment C<br>* During Part 2 of the study, participants will receive single doses of selumetinib 25 mg granule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Treatment D<br>* During Part 2 of the study, participants will receive single doses of selumetinib 50 mg capsule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Acetaminophen<br>* Participants will receive a single 500mg dose of acetaminophen at the same time.<br>|
| Experimental: Treatment Sequence 2<br>Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 3 and Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 4. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration where it will act as a marker for gastric emptying. | Drug: Treatment A<br>* During Part 1 of the study, participants will receive single doses of selumetinib 25 mg granule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment B<br>* During Part 1 of the study, participants will receive single doses of selumetinib 50 mg capsule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment C<br>* During Part 2 of the study, participants will receive single doses of selumetinib 25 mg granule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Treatment D<br>* During Part 2 of the study, participants will receive single doses of selumetinib 50 mg capsule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Acetaminophen<br>* Participants will receive a single 500mg dose of acetaminophen at the same time.<br>|
| Experimental: Treatment Sequence 3<br>Participants will receive Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 1, Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration where it will act as a marker for gastric emptying. | Drug: Treatment A<br>* During Part 1 of the study, participants will receive single doses of selumetinib 25 mg granule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment B<br>* During Part 1 of the study, participants will receive single doses of selumetinib 50 mg capsule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment C<br>* During Part 2 of the study, participants will receive single doses of selumetinib 25 mg granule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Treatment D<br>* During Part 2 of the study, participants will receive single doses of selumetinib 50 mg capsule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Acetaminophen<br>* Participants will receive a single 500mg dose of acetaminophen at the same time.<br>|
| Experimental: Treatment Sequence 4<br>Participants will receive Treatment B (selumetinib 50 mg capsule, fasted state) in Part 1, Period 1, Treatment A (selumetinib 25 mg granule, fasted state) in Part 1, Period 2, Treatment D (selumetinib 50 mg capsule, fed state) in Part 2, Period 3 and Treatment C (selumetinib 25 mg granule, fed state) in Part 2, Period 4. Participants will also receive a single 500 mg dose of acetaminophen at the same time as selumetinib administration where it will act as a marker for gastric emptying. | Drug: Treatment A<br>* During Part 1 of the study, participants will receive single doses of selumetinib 25 mg granule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment B<br>* During Part 1 of the study, participants will receive single doses of selumetinib 50 mg capsule under fasted conditions. The dose will be administered after an overnight fast of at least 10 hours. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose.<br>Drug: Treatment C<br>* During Part 2 of the study, participants will receive single doses of selumetinib 25 mg granule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Treatment D<br>* During Part 2 of the study, participants will receive single doses of selumetinib 50 mg capsule under fed conditions. Following an overnight fast of at least 10 hours, participants will start consumption of the recommended meal within 30 minutes before administration of the IMP. Participants will be required to consume the entire meal in 30 minutes or less; however, the IMP should be administered 30 minutes after start of the meal. The IMP will be administered with approximately 240 mL of water. No food will be allowed for at least 4 hours post-dose, where after a meal may be provided.<br>Drug: Acetaminophen<br>* Participants will receive a single 500mg dose of acetaminophen at the same time.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Dose normalized area under plasma concentration-time curve from time zero to infinity (AUC/D) | To compare the AUC/D of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Dose normalized area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast/D) | To compare the AUClast/D of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Dose normalized maximum observed plasma concentration (Cmax/D) | To compare the Cmax/D of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Fraction of administered selumetinib granule dose systemically available relative to the capsule reference (Frel) | To compare the Frel. of the new selumetinib granule formulation with selumetinib capsule formulation in fasted state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Area under plasma concentration time curve from time zero to infinity (AUC) | To compare AUC of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose(Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Area under the plasma concentration time curve from time zero to time of last quantifiable concentration (AUClast) | To compare AUClast of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Area under the plasma concentration-time curve from zero to 12 hours post-dose [AUC(0-12)] | To compare AUC (0-12) of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Maximum observed plasma concentration (Cmax) | To compare Cmax of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Ratio of AUC in fed state to AUC in the fasted state (FRAUC) | To compare FRAUC of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Ratio of Cmax in fed state to Cmax in the fasted state (FRCmax) | To compare FRCmax of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) | To compare t½λz of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Time to reach maximum observed plasma concentration (tmax) | To compare tmax of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Terminal elimination rate constant (λz) | To compare λz of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib plasma PK parameters: Apparent total body clearance of drug from plasma after extravascular administration (parent drug only) (CL/F) | To compare CL/F of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib plasma PK parameters: Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) | To compare Vz/F of selumetinib capsule fasted versus capsule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: AUC | To compare AUC of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: AUClast | To compare AUClast of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: AUC(0-12) | To compare AUC (0-12) of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: Cmax | To compare Cmax of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: FRAUC | To compare FRAUC of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: FRCmax | To compare FRCmax of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: t½λz | To compare t½λz of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: tmax | To compare tmax of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib and N-desmethyl selumetinib plasma PK parameter: λz | To compare λz of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib plasma PK parameters: CL/F | To compare CL/F of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Selumetinib plasma PK parameters: Vz/F | To compare Vz/F of selumetinib granule fasted versus granule low-fat fed state. | At pre-dose, and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36 and 48 hours post-dose (Days -1 to 3) |
| Taste questionnaire | To assess palatability of selumetinib granule formulation. The standardized questionnaire will be administered to participants within 10 minutes following intake of selumetinib granule. Questionnaire about taste include sweet, salty, sour, bitter, metallic, and hot/spicy. Where 0 indicates not at all and 10 indicates extremely. | At Days -1 to 3 (within 10 minutes following intake of selumetinib granule) |
| Number of participants with adverse events (AEs) | To assess the safety and tolerability of single doses of selumetinib in healthy participants. | From the time of informed consent, throughout the treatment periods up to and including the Follow-up Visit (7 to 10 days after last dose) |
| Vital signs (systolic blood pressure [BP]) | To assess systolic BP as a variable of safety and tolerability of single doses of selumetinib in healthy participants. Participants should be supine and at rest for at least 5 minutes before the measurements. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Vital signs (diastolic BP) | To assess diastolic BP as a variable of safety and tolerability of single doses of selumetinib in healthy participants. Participants should be supine and at rest for at least 5 minutes before the measurements. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Pulse rate | To assess pulse rate as a variable of safety and tolerability of single doses of selumetinib in healthy participants. Participants should be supine and at rest for at least 5 minutes before the measurements. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| 12-lead electrocardiogram (ECG) | To assess 12-lead ECG as variable of safety and tolerability of single doses of selumetinib in healthy participants. Participants should be supine and at rest 10 minutes before recording the ECG. | From baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Number of participants with abnormal findings in physical examination | To assess physical examination as a variable safety and tolerability of single doses of selumetinib in healthy participants. | From baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Ophthalmic examinations | To assess ophthalmic examination as a variable of safety and tolerability of single doses of selumetinib in healthy participants. Ophthalmic examination included best corrected visual acuity, intra-ocular pressure and slit-lamp fundoscopy. | At screening Visit or on Day -1 of Treatment Period 1 |
| Laboratory assessments: hematology - Hemoglobin (Hb) | To assess Hb as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: hematology - erythrocyte count | To assess erythrocyte count as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: hematology: Platelet count | To assess platelet count as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: hematology: leucocyte differential count (absolute count) | To assess leucocyte differential count as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: hematology: leucocyte cell count | To assess leucocyte cell count as variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments:hematology - differential count | To assess differential count of neutrophils, lymphocytes, monocyets, eosinophils and basophils) as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry - electrolytes | To assess serum level of sodium, potassium, magnesium and phosphate as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry - urea nitrogen | To assess urea nitrogen as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry - creatinine | To assess creatinine as variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: albumin | To assess albumin as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: Total Calcium | To assess total calcium as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: Total protein | To assess total protein as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: Total bilirubin | To assess total bilirubin as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: Creatine phosphokinase (CPK) | To assess CPK as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry: Troponin (isoform as per institutional norm) | To assess troponin as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Serum clinical chemistry - Liver enzymes | To assess serum of Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Gamma glutamyl transpeptidase (GGT) as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Clinical urinalysis - glucose | To assess urine glucose as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Clinical Urinalysis - protein | To assess urine protein as a variable of safety and tolerability of single doses of selumetinib in healthy participants. | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
| Laboratory assessments: Clinical Urinalysis - blood | To assess urine blood as a variable of safety and tolerability of single doses of selumetinib in healthy participants. If urinalysis is positive for blood, a microscopy test will be performed to assess RBC, white blood cell [WBC], casts [cellular, granular, hyaline]). | Change from baseline up to follow-up/early termination visit (7 to 10 days after last dose) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MEK Inhibitor, Selumetinib capsule, Selumetinib granule, PK, Bioavailibilty, Crossover study, Open-label, Food effect
|
NCT02683304
|
S100B in the Care of Non-traumatic Headaches in the Emergency Department
|
The main objective of this pilot study is to make a first assessment of the discriminating ability of a dosage of S100B protein for differential diagnosis between primary headaches and secondary headaches.~For this, the investigators will compare serum S100B protein between two groups of headache patients presenting at the emergency department: 1 group of primary headache patients and 1 group of secondary headache patients.~If the difference between the two groups proves potentially discriminating, the investigators will seek to determine the discriminating ability of the S100B protein by calculating the area under the ROC curve.~The reference diagnostic will be set at one month across the entire clinical picture and imaging by an expert committee composed of a neurologist, a radiologist and an emergency physician.
|
The secondary objectives of this study are:~A. To seek an association between S100B protein levels and the onset of pain depending on whether it is more or less than 3 hours.~B. To assess the association between S100B protein levels and mortality at day 28.~C. To evaluate the association between S100B protein levels and hospital care: average length of stay in the emergency department, lumbar puncture, brain imaging, average length of hospital stay.~D. To evaluate the prognostic value of determination of S100B protein on the occurrence of a secondary headache at 1 month.
|
S100B Protein Measures in the Care of Non-traumatic Headaches in the Emergency Department
|
Headache
|
* Biological: Plasma S100B levels at inclusion
* Device: Magnetic resonance imaging
|
Inclusion Criteria:~The patient must have given his/her informed and signed consent~The patient must be insured or beneficiary of a health insurance plan~The patient has nontraumatic headache pain with a visual analog scale > 3~Exclusion Criteria:~The patient is participating in another study~The patient is in an exclusion period determined by a previous study~The patient is under judicial protection, under tutorship or curatorship~The patient refuses to sign the consent~It is impossible to correctly inform the patient~The patient is pregnant, parturient, or breastfeeding~The patient has a contraindication for magnetic resonance imaging~Patients suffering from the following diseases: Alzheimer's disease, multiple sclerosis, Creutzfeldt-Jakob disease, melanoma, trisomy 21.
|
18 Years
|
59 Years
|
All
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| S100B protein level (ng/ml) | | Day 0 |
| The presence/absence of a clinically significant anomaly on the MRI scan | | Days 2-4 |
| Final diagnostic as established by an expert committee | The diagnostic posed is either primary headache or secondary headache | Month 1 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality (yes/no) | Mortality refers to whether or not the subject is still alive. | Month 1 |
| Length of stay in the emergency department (days) | | Month 1 |
| Length of stay in the hospital (days) | | Month 1 |
| White blood cell count in cerebral spinal fluid | | Month 1 |
| Red blood cell count in cerebral spinal fluid | | Month 1 |
| Cerebral spinal fluid glucose level | | Month 1 |
| Cerebral spinal fluid protein level | | Month 1 |
| Cerebral spinal fluid chloride level | | Month 1 |
| Presence/absence of enterovirus in cerebral spinal fluid | Based on qualitative result from ELISA laboratory exam. | Month 1 |
| Presence/absence of herpes virus in cerebral spinal fluid | Based on qualitative result from ELISA laboratory exam. | Month 1 |
| Presence/absence of cerebral imaging indicating an ischemic or hemorrhagic stroke, subarachnoid hemorrhage, an expansive process, cerebral trombophlebitis cerebral or other abnormalities suggestive of a secondary cause of headache. | | Month 1 |
| Secondary headache onset: yes/no | Was there secondary headache onset by month 1? | Month 1 |
|
Emergencies, Headache, Disease Attributes, Pathologic Processes, Pain, Neurologic Manifestations
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The study population<br>The study population consists of consecutive headache patients (visual analogue scale > 3) presenting at the emergency department of the Nîmes University Hospital | Biological: Plasma S100B levels at inclusion<br>* Patients will have blood drawn to measure plasma S100B levels at inclusion.<br>Device: Magnetic resonance imaging<br>* If not performed under emergency conditions, patients will have an MRI on days 2-4.<br>|
|
S100B in the Care of Non-traumatic Headaches in the Emergency Department
Study Overview
=================
Brief Summary
-----------------
The main objective of this pilot study is to make a first assessment of the discriminating ability of a dosage of S100B protein for differential diagnosis between primary headaches and secondary headaches. For this, the investigators will compare serum S100B protein between two groups of headache patients presenting at the emergency department: 1 group of primary headache patients and 1 group of secondary headache patients. If the difference between the two groups proves potentially discriminating, the investigators will seek to determine the discriminating ability of the S100B protein by calculating the area under the ROC curve. The reference diagnostic will be set at one month across the entire clinical picture and imaging by an expert committee composed of a neurologist, a radiologist and an emergency physician.
Detailed Description
-----------------
The secondary objectives of this study are: A. To seek an association between S100B protein levels and the onset of pain depending on whether it is more or less than 3 hours. B. To assess the association between S100B protein levels and mortality at day 28. C. To evaluate the association between S100B protein levels and hospital care: average length of stay in the emergency department, lumbar puncture, brain imaging, average length of hospital stay. D. To evaluate the prognostic value of determination of S100B protein on the occurrence of a secondary headache at 1 month.
Official Title
-----------------
S100B Protein Measures in the Care of Non-traumatic Headaches in the Emergency Department
Conditions
-----------------
Headache
Intervention / Treatment
-----------------
* Biological: Plasma S100B levels at inclusion
* Device: Magnetic resonance imaging
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The patient must have given his/her informed and signed consent The patient must be insured or beneficiary of a health insurance plan The patient has nontraumatic headache pain with a visual analog scale > 3 Exclusion Criteria: The patient is participating in another study The patient is in an exclusion period determined by a previous study The patient is under judicial protection, under tutorship or curatorship The patient refuses to sign the consent It is impossible to correctly inform the patient The patient is pregnant, parturient, or breastfeeding The patient has a contraindication for magnetic resonance imaging Patients suffering from the following diseases: Alzheimer's disease, multiple sclerosis, Creutzfeldt-Jakob disease, melanoma, trisomy 21.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 59 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The study population<br>The study population consists of consecutive headache patients (visual analogue scale > 3) presenting at the emergency department of the Nîmes University Hospital | Biological: Plasma S100B levels at inclusion<br>* Patients will have blood drawn to measure plasma S100B levels at inclusion.<br>Device: Magnetic resonance imaging<br>* If not performed under emergency conditions, patients will have an MRI on days 2-4.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| S100B protein level (ng/ml) | | Day 0 |
| The presence/absence of a clinically significant anomaly on the MRI scan | | Days 2-4 |
| Final diagnostic as established by an expert committee | The diagnostic posed is either primary headache or secondary headache | Month 1 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality (yes/no) | Mortality refers to whether or not the subject is still alive. | Month 1 |
| Length of stay in the emergency department (days) | | Month 1 |
| Length of stay in the hospital (days) | | Month 1 |
| White blood cell count in cerebral spinal fluid | | Month 1 |
| Red blood cell count in cerebral spinal fluid | | Month 1 |
| Cerebral spinal fluid glucose level | | Month 1 |
| Cerebral spinal fluid protein level | | Month 1 |
| Cerebral spinal fluid chloride level | | Month 1 |
| Presence/absence of enterovirus in cerebral spinal fluid | Based on qualitative result from ELISA laboratory exam. | Month 1 |
| Presence/absence of herpes virus in cerebral spinal fluid | Based on qualitative result from ELISA laboratory exam. | Month 1 |
| Presence/absence of cerebral imaging indicating an ischemic or hemorrhagic stroke, subarachnoid hemorrhage, an expansive process, cerebral trombophlebitis cerebral or other abnormalities suggestive of a secondary cause of headache. | | Month 1 |
| Secondary headache onset: yes/no | Was there secondary headache onset by month 1? | Month 1 |
|
|
NCT03016429
|
Safety and Clinical Outcomes of Magnetic Resonance Imaging in Patients With Cardiac Implantable Electrical Devices
|
This protocol outlines a prospective study evaluating safety and clinical outcomes of magnetic resonance imaging (MRI) examinations performed on patients with cardiac implantable electrical devices (CIEDs) including pacemakers (PMs) and implantable cardioverter-defibrillators (ICDs). This prospective study aims to improve the evidence base regarding this common clinical scenario. Specifically, the investigators aim to address whether results of MRI in PM/ICD patients affect physician decision making related to clinical management strategy and planning treatment interventions. Further, this study will evaluate whether the results of MRI in these patients affects patient outcomes related to survival and adverse events during or after MRI scanning.
|
MRI is the preferred imaging modality for both acute and elective evaluation of many conditions. For example, for many diseases of the central nervous system, no other imaging modality provides the requisite soft tissue resolution to support critical care elements such as neurosurgical planning or assessment of intracranial malignancies.~Historically, MRIs were considered contraindicated for patients with CIEDs including PMs and ICDs. However, studies have demonstrated very high utilization of MRIs among patients eligible for CIEDs. In many cases, alternative imaging is either insufficient or, as with CT-myelography, poses substantial risks or procedural hurdles that may be less favorable than the potential risks of an MRI.~In recent years, a growing literature has suggested that MRIs can be performed safely in the setting of CIEDs if certain precautions are taken. Additionally, guidance documents have been released by professional societies including the American Heart Association (AHA) and the American College of Radiology (ACR) outlining recommended safety measures that can be taken to minimize risk and maximize benefit for patients in need of imaging. However, there are fewer data on performing MRIs in pacemaker-dependent patients with ICDs, who were excluded from the largest published study as well as the MagnaSafe Registry. Thus, demonstrating the safety and clinical utility of performing MRIs in this context is of high importance.~In response to urgent clinical considerations, Beth Israel Deaconess Medical Center has established a clinical protocol to provide safe MRIs in cases of compelling clinical indications, with close supervision and oversight from Radiology and Cardiac Electrophysiology staff. Thus, the investigators now propose a prospective study to evaluate safety and clinical outcomes for patients treated under this clinical protocol.~Specifically, this study proposes to perform a prospective clinical trial in patients with CIEDs that have a clinical need for MRI as outpatients to determine:~Safety according to the incidence rates of acute major and minor adverse events according to pre-specified definitions.~Clinical outcomes and scan utility affecting patients' survival and quality of life and treatment, including acute and longitudinal changes in device parameters, the need for system revision, and proportion of MRI findings influencing clinical management including medical or surgical interventions, and diagnostic or prognostic changes.
|
Safety and Clinical Outcomes of Magnetic Resonance Imaging in Patients With Cardiac Implantable Electrical Devices
|
Cardiac Disease
|
Inclusion Criteria:~Patients have a medically/clinically indicated need for an MRI~Patients with a non-MRI conditional pacemaker and/or ICD implanted after the year 2000~Patients are willing and able to sign consent and HIPAA authorization or an authorized representative of the patient is willing to sign consent for the patient~*The following factors are considered relative contraindications to the clinical protocol at BIDMC, and will similarly be considered exclusion criteria for the study. Exceptions on a case-by-case basis for circumstances of dire, life-threatening need may be considered.~Leads implanted <6 weeks prior to the MRI~Presence of any capped/abandoned leads~Presence of nontransvenous epicardial leads~Exclusion Criteria:~Other contraindications to MRI (e.g. other non-MRI-conditional implants)~Pacemaker or ICD implanted prior to the year 2000~Leads and/or generator implanted within 6 weeks of the proposed MRI~CIED that is FDA approved as MRI conditional~Pregnant women
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients with Any of the Following Major Adverse Events | Acute loss of pacing peri-MRI (defined in scanner, or after scan prior to discharge)~Inappropriate shock or ATP therapy peri-MRI~Any death peri-MRI adjudicated to be related to the scan | Change from baseline at 1 week and 6 months |
| Number of Patients with Any of the Following Minor Adverse Events | Clinically significant (symptoms or hemodynamic compromise) inappropriate pacing (e.g. undersensing or inappropriate asynchronous pacing)~Any clinically significant arrhythmias peri-MRI~Power-on-reset events~Acute variation in pre/post MRI capture thresholds ≥ 50%~Acute variation in pre/post MRI lead impedance ≥ 30%~Acute variation in pre/post MRI P/R wave amplitude ≥ 50% | Change from baseline at 1 week and 6 months |
|
pacemaker, defibrillator, magnetic resonance imaging, cardiac implantable electronic device
|
Heart Diseases, Cardiovascular Diseases
|
Safety and Clinical Outcomes of Magnetic Resonance Imaging in Patients With Cardiac Implantable Electrical Devices
Study Overview
=================
Brief Summary
-----------------
This protocol outlines a prospective study evaluating safety and clinical outcomes of magnetic resonance imaging (MRI) examinations performed on patients with cardiac implantable electrical devices (CIEDs) including pacemakers (PMs) and implantable cardioverter-defibrillators (ICDs). This prospective study aims to improve the evidence base regarding this common clinical scenario. Specifically, the investigators aim to address whether results of MRI in PM/ICD patients affect physician decision making related to clinical management strategy and planning treatment interventions. Further, this study will evaluate whether the results of MRI in these patients affects patient outcomes related to survival and adverse events during or after MRI scanning.
Detailed Description
-----------------
MRI is the preferred imaging modality for both acute and elective evaluation of many conditions. For example, for many diseases of the central nervous system, no other imaging modality provides the requisite soft tissue resolution to support critical care elements such as neurosurgical planning or assessment of intracranial malignancies. Historically, MRIs were considered contraindicated for patients with CIEDs including PMs and ICDs. However, studies have demonstrated very high utilization of MRIs among patients eligible for CIEDs. In many cases, alternative imaging is either insufficient or, as with CT-myelography, poses substantial risks or procedural hurdles that may be less favorable than the potential risks of an MRI. In recent years, a growing literature has suggested that MRIs can be performed safely in the setting of CIEDs if certain precautions are taken. Additionally, guidance documents have been released by professional societies including the American Heart Association (AHA) and the American College of Radiology (ACR) outlining recommended safety measures that can be taken to minimize risk and maximize benefit for patients in need of imaging. However, there are fewer data on performing MRIs in pacemaker-dependent patients with ICDs, who were excluded from the largest published study as well as the MagnaSafe Registry. Thus, demonstrating the safety and clinical utility of performing MRIs in this context is of high importance. In response to urgent clinical considerations, Beth Israel Deaconess Medical Center has established a clinical protocol to provide safe MRIs in cases of compelling clinical indications, with close supervision and oversight from Radiology and Cardiac Electrophysiology staff. Thus, the investigators now propose a prospective study to evaluate safety and clinical outcomes for patients treated under this clinical protocol. Specifically, this study proposes to perform a prospective clinical trial in patients with CIEDs that have a clinical need for MRI as outpatients to determine: Safety according to the incidence rates of acute major and minor adverse events according to pre-specified definitions. Clinical outcomes and scan utility affecting patients' survival and quality of life and treatment, including acute and longitudinal changes in device parameters, the need for system revision, and proportion of MRI findings influencing clinical management including medical or surgical interventions, and diagnostic or prognostic changes.
Official Title
-----------------
Safety and Clinical Outcomes of Magnetic Resonance Imaging in Patients With Cardiac Implantable Electrical Devices
Conditions
-----------------
Cardiac Disease
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients have a medically/clinically indicated need for an MRI Patients with a non-MRI conditional pacemaker and/or ICD implanted after the year 2000 Patients are willing and able to sign consent and HIPAA authorization or an authorized representative of the patient is willing to sign consent for the patient *The following factors are considered relative contraindications to the clinical protocol at BIDMC, and will similarly be considered exclusion criteria for the study. Exceptions on a case-by-case basis for circumstances of dire, life-threatening need may be considered. Leads implanted <6 weeks prior to the MRI Presence of any capped/abandoned leads Presence of nontransvenous epicardial leads Exclusion Criteria: Other contraindications to MRI (e.g. other non-MRI-conditional implants) Pacemaker or ICD implanted prior to the year 2000 Leads and/or generator implanted within 6 weeks of the proposed MRI CIED that is FDA approved as MRI conditional Pregnant women
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients with Any of the Following Major Adverse Events | Acute loss of pacing peri-MRI (defined in scanner, or after scan prior to discharge) Inappropriate shock or ATP therapy peri-MRI Any death peri-MRI adjudicated to be related to the scan | Change from baseline at 1 week and 6 months |
| Number of Patients with Any of the Following Minor Adverse Events | Clinically significant (symptoms or hemodynamic compromise) inappropriate pacing (e.g. undersensing or inappropriate asynchronous pacing) Any clinically significant arrhythmias peri-MRI Power-on-reset events Acute variation in pre/post MRI capture thresholds ≥ 50% Acute variation in pre/post MRI lead impedance ≥ 30% Acute variation in pre/post MRI P/R wave amplitude ≥ 50% | Change from baseline at 1 week and 6 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pacemaker, defibrillator, magnetic resonance imaging, cardiac implantable electronic device
|
||||
NCT01046435
|
Effects of Periodontal Therapy on Systemic Inflammation
|
The purpose of this study is to determine if treating periodontal infections (gum disease) will reduce markers of systemic inflammation in patients at risk of cardiovascular diseases.
|
Aims: To determine the effects of periodontal treatment on systemic markers of inflammation in subjects with risk of coronary heart disease.~Methods: The current study is a randomized, double blind clinical trial, with two treatment groups.~Eligible participants will be allocated by restricted randomization using the minimization method to the treatment group or to the control group. The treatment group will receive periodontal therapy consisting of instructions of plaque control, supra and subgingival scaling and root planing, oral systemic metronidazole (250 mg) plus amoxicillin (500 mg) tid for 7 days. The control group will receive plaque control instructions, supragingival scaling and two placebos. The study plan to enroll 160 participants, 80 in ech arm, over a 6-month period. Follow-up clinic visits will be scheduled to occur every 3 months after finishing treatment. Baseline and follow-up clinic visits will include periodontal examination, blood collection and medical and dental histories. The following biochemical markers will be determined at baseline and at 3, 6, 9 and 12 months posttherapy: total, LDL and HDL lipoprotein cholesterol and triglycerides, glycemia, high sensitivity C-reactive protein, fibrinogen, erythrocyte sedimentation rate and white blood cells count. In diabetic patients, glycosylated hemoglobin will be also assessed.~The study will be conducted in a public health center in Santiago, Chile. To be eligible for the study, participants have to be older than 35 years and fulfill the medical and periodontal criteria. For the medical criteria participants have to have dyslipidemia, and at least one of the following coronary heart disease risk factors: obesity, smoking, diabetes, hypertension.~The periodontal inclusion criteria are: no history of periodontal treatment, the presence of at least 14 natural teeth, with at least 4 teeth with interproximal sites with probing depth equal or higher than 4 mm and concomitant attachment loss equal or higher than 3 mm, and >30 % of sites with bleeding on probing.~The outcomes measures will be levels of serum C-reactive protein, fibrinogen, erythrosedimentation rate, white blood cell count.The outcomes will be measured at 0, 3,6,9, and 6 months after periodontal therapy.
|
Effects of Periodontal Therapy on Markers of Systemic Inflammation in Subjects at Cardiovascular Disease Risk
|
Periodontal Disease, Cardiovascular Disease, Type 2 Diabetes, Obesity, Metabolic Syndrome
|
* Procedure: metronidazole and amoxicillin
* Procedure: Two placebos
|
Inclusion Criteria:~Clinically diagnosis of marginal periodontitis~No history of periodontal treatment~At least 14 natural teeth present~Dyslipidemia~And at least one of the following factors:~obesity~diabetes~smoking, hypertension~Exclusion Criteria:~Rheumatoid arthritis~Any type of cancer in the previous 2 years~Pregnancy and lactation~Indication of the use of antibiotic for invasive procedures~Use of antibiotics in previous three months.
|
35 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum levels of C-reactive protein, fibrinogen,erythrosedimentation rate and white blood cell count | | 0, 3, 6, 9 and 12 months after therapy |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical periodontal parameters: probing depth, bleeding on probing, clinical attachment level | | 0, 3, 6, 9 and 12 months after therapy |
|
periodontitis, cardiovascular disease, diabetes
|
Amoxicillin, Metronidazole, Anti-Bacterial Agents, Anti-Infective Agents, Antiprotozoal Agents, Antiparasitic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Supragingival scaling plus placebo<br>Plaque control instructions, supra gingival scaling and two placebos | Procedure: metronidazole and amoxicillin<br>* Metronidazole 250 mg three times a day per 7 days<br>* Other names: Non-surgical periodontal therapy;Procedure: Two placebos<br>* Two placebos 3 times a day for 7 days<br>* Other names: Community periodontal treatment;|
| Experimental: Root planing plus antibiotics<br>Plaque control instructions, subgingival scaling,root planing, metronidazole 250 mg and amoxicillin 500 mg. three times a day for 7 days | Procedure: metronidazole and amoxicillin<br>* Metronidazole 250 mg three times a day per 7 days<br>* Other names: Non-surgical periodontal therapy;Procedure: Two placebos<br>* Two placebos 3 times a day for 7 days<br>* Other names: Community periodontal treatment;|
|
Effects of Periodontal Therapy on Systemic Inflammation
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if treating periodontal infections (gum disease) will reduce markers of systemic inflammation in patients at risk of cardiovascular diseases.
Detailed Description
-----------------
Aims: To determine the effects of periodontal treatment on systemic markers of inflammation in subjects with risk of coronary heart disease. Methods: The current study is a randomized, double blind clinical trial, with two treatment groups. Eligible participants will be allocated by restricted randomization using the minimization method to the treatment group or to the control group. The treatment group will receive periodontal therapy consisting of instructions of plaque control, supra and subgingival scaling and root planing, oral systemic metronidazole (250 mg) plus amoxicillin (500 mg) tid for 7 days. The control group will receive plaque control instructions, supragingival scaling and two placebos. The study plan to enroll 160 participants, 80 in ech arm, over a 6-month period. Follow-up clinic visits will be scheduled to occur every 3 months after finishing treatment. Baseline and follow-up clinic visits will include periodontal examination, blood collection and medical and dental histories. The following biochemical markers will be determined at baseline and at 3, 6, 9 and 12 months posttherapy: total, LDL and HDL lipoprotein cholesterol and triglycerides, glycemia, high sensitivity C-reactive protein, fibrinogen, erythrocyte sedimentation rate and white blood cells count. In diabetic patients, glycosylated hemoglobin will be also assessed. The study will be conducted in a public health center in Santiago, Chile. To be eligible for the study, participants have to be older than 35 years and fulfill the medical and periodontal criteria. For the medical criteria participants have to have dyslipidemia, and at least one of the following coronary heart disease risk factors: obesity, smoking, diabetes, hypertension. The periodontal inclusion criteria are: no history of periodontal treatment, the presence of at least 14 natural teeth, with at least 4 teeth with interproximal sites with probing depth equal or higher than 4 mm and concomitant attachment loss equal or higher than 3 mm, and >30 % of sites with bleeding on probing. The outcomes measures will be levels of serum C-reactive protein, fibrinogen, erythrosedimentation rate, white blood cell count.The outcomes will be measured at 0, 3,6,9, and 6 months after periodontal therapy.
Official Title
-----------------
Effects of Periodontal Therapy on Markers of Systemic Inflammation in Subjects at Cardiovascular Disease Risk
Conditions
-----------------
Periodontal Disease, Cardiovascular Disease, Type 2 Diabetes, Obesity, Metabolic Syndrome
Intervention / Treatment
-----------------
* Procedure: metronidazole and amoxicillin
* Procedure: Two placebos
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinically diagnosis of marginal periodontitis No history of periodontal treatment At least 14 natural teeth present Dyslipidemia And at least one of the following factors: obesity diabetes smoking, hypertension Exclusion Criteria: Rheumatoid arthritis Any type of cancer in the previous 2 years Pregnancy and lactation Indication of the use of antibiotic for invasive procedures Use of antibiotics in previous three months.
Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Supragingival scaling plus placebo<br>Plaque control instructions, supra gingival scaling and two placebos | Procedure: metronidazole and amoxicillin<br>* Metronidazole 250 mg three times a day per 7 days<br>* Other names: Non-surgical periodontal therapy;Procedure: Two placebos<br>* Two placebos 3 times a day for 7 days<br>* Other names: Community periodontal treatment;|
| Experimental: Root planing plus antibiotics<br>Plaque control instructions, subgingival scaling,root planing, metronidazole 250 mg and amoxicillin 500 mg. three times a day for 7 days | Procedure: metronidazole and amoxicillin<br>* Metronidazole 250 mg three times a day per 7 days<br>* Other names: Non-surgical periodontal therapy;Procedure: Two placebos<br>* Two placebos 3 times a day for 7 days<br>* Other names: Community periodontal treatment;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum levels of C-reactive protein, fibrinogen,erythrosedimentation rate and white blood cell count | | 0, 3, 6, 9 and 12 months after therapy |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical periodontal parameters: probing depth, bleeding on probing, clinical attachment level | | 0, 3, 6, 9 and 12 months after therapy |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
periodontitis, cardiovascular disease, diabetes
|
NCT04284631
|
Prognostic Value of Her2neu and EGFR in Primary Ovarian High Grade Serous Carcinoma.
|
To assess alterations of EGFR& Her2neu expression in primary ovarian high grade serous carcinoma and its correlation with other clinicopathological parameters
|
Ovarian cancer (OC) is the seventh most common cancer and the fifth cause of cancer death in women worldwide. The most frequent type is surface epithelial tumors. It is frequently diagnosed at advanced stages. So, it is referred to as silent killer.~Serous carcinoma is the most common and aggressive type of epithelial ovarian cancer . Serous carcinomas are currently separated into two completely different subtypes either histologically or biologically, lowg rade and high grade, based on both degree of nuclear atypia and the number of mitoses.~Current therapy is based on few traditional prognostic factors, such as tumor stage and postoperative tumor residual mass. Identification of new molecular markers could help in significant modification of treatmant improving clinical prognosis The ErbB family of tyrosine kinase receptors (epidermal growth factor (EGF) receptors) plays a role in the tumorigenesis of several types of solid tumors. The abnormal activation of these receptors has been associated with various pathological processes especially cellular transformation .~EGFR is involved in various stages of cancer growth, such as tumor initiation, angiogenesis and metastasis. Also, it participates by various pathways as a proto-oncogene in several types of cancers such as gastrointestinal and breast ones. So, it is an attractive target for oncogenic therapy HER2 protooncogene is involved in the development of many types of human cancer and is used as therapeutic target. Although the association between HER2 expression and ovarian cancer has been widely studied, the results are still controversial Therefore, in the present study we will analyze the expression of both EGFR& Her2neu in an OC tissue microarray (TMA) by immunohistochemistry, and results were be correlated to other clinicopathological parameters and prognosis.~Aim of the study:~General aim: To assess alterations of EGFR& Her2neu expression in primary ovarian high grade serous carcinoma and its correlation with other clinicopathological parameters.~Specific objectives:~To measure the frequency of EGFR& Her2neu immunohistochemical expression in ovarian high grade serous carcinoma.~To correlate between expression of EGFR& Her2neu expression and other clinicopathological parameters of ovarian high grade serous carcinoma~To correlate between expression of EGFR& Her2neu expression and prognosis of ovarian high grade serous carcinoma~Materials:~This cross-sectional study will be done on 54 specimens of ovarian primary high grade serous carcinoma cases who attended to Oncology Centre, Mansoura University, Mansoura, Egypt since 2012 to the end of 5 years follow up of the last patient The cases will be chosen randomly.~Methods:~All clinicopathological data of these cases will be collected such as Tumor size, LN metastases (N), metastasis (M), ascites, residual tumor, peritoneal deposits, recurrence, TNM staging & (FIGO) staging system.~Prepare hematoxylin & eosin slides to diagnose and assess other histopathological parameters such as histological type~Immunohistochemistry:~Sections 4μm thickness from newly formed tissue microarray blocks will be cut on coated slides then immunohistochemical staining using antibody against EGFR& Her2neu will be done.~Statistical analysis:~SPSS software version 20 (SPSS Inc., Chicago, IL) will be used for analysis. For nominal variables, proportions and X2 tests will be applied, whereas for interval variables means, standard deviations (SD), and T test and ANOVA tests will be applied where appropriate. Kaplan-Meier method will be used for survival analysis. Chi-square test was used to estimate the relation between qualitative variables. Mann-Whitney test (non-parametric t test) was used for not normally distributed quantitative data, for comparison between two groups while, comparison between three groups was done using Kruskal-Wallis test (non-parametric ANOVA).
|
Prognostic Value of Her2neu and EGFR in Primary Ovarian High Grade Serous Carcinoma.
|
Ovarian Cancer
|
Inclusion Criteria:~Patients with primary ovarian cancer~Exclusion Criteria:~patients with secondary ovarian cancer
| null | null |
Female
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EGFR& Her2neu expression to the grade of ovarian serous carcinoma | EGFR& Her2neu expression in primary ovarian high grade serous carcinoma | 2 years |
| EGFR& Her2neu expression in primary ovarian serous carcinoma to prognosis | Expression of EGFR & Her2neu in primary ovarian cancer to cancer free period | 5 years |
|
Cystadenocarcinoma, Serous, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Cystadenocarcinoma, Adenocarcinoma, Neoplasms, Cystic, Mucinous, and Serous, Carcinoma
|
Prognostic Value of Her2neu and EGFR in Primary Ovarian High Grade Serous Carcinoma.
Study Overview
=================
Brief Summary
-----------------
To assess alterations of EGFR& Her2neu expression in primary ovarian high grade serous carcinoma and its correlation with other clinicopathological parameters
Detailed Description
-----------------
Ovarian cancer (OC) is the seventh most common cancer and the fifth cause of cancer death in women worldwide. The most frequent type is surface epithelial tumors. It is frequently diagnosed at advanced stages. So, it is referred to as silent killer. Serous carcinoma is the most common and aggressive type of epithelial ovarian cancer . Serous carcinomas are currently separated into two completely different subtypes either histologically or biologically, lowg rade and high grade, based on both degree of nuclear atypia and the number of mitoses. Current therapy is based on few traditional prognostic factors, such as tumor stage and postoperative tumor residual mass. Identification of new molecular markers could help in significant modification of treatmant improving clinical prognosis The ErbB family of tyrosine kinase receptors (epidermal growth factor (EGF) receptors) plays a role in the tumorigenesis of several types of solid tumors. The abnormal activation of these receptors has been associated with various pathological processes especially cellular transformation . EGFR is involved in various stages of cancer growth, such as tumor initiation, angiogenesis and metastasis. Also, it participates by various pathways as a proto-oncogene in several types of cancers such as gastrointestinal and breast ones. So, it is an attractive target for oncogenic therapy HER2 protooncogene is involved in the development of many types of human cancer and is used as therapeutic target. Although the association between HER2 expression and ovarian cancer has been widely studied, the results are still controversial Therefore, in the present study we will analyze the expression of both EGFR& Her2neu in an OC tissue microarray (TMA) by immunohistochemistry, and results were be correlated to other clinicopathological parameters and prognosis. Aim of the study: General aim: To assess alterations of EGFR& Her2neu expression in primary ovarian high grade serous carcinoma and its correlation with other clinicopathological parameters. Specific objectives: To measure the frequency of EGFR& Her2neu immunohistochemical expression in ovarian high grade serous carcinoma. To correlate between expression of EGFR& Her2neu expression and other clinicopathological parameters of ovarian high grade serous carcinoma To correlate between expression of EGFR& Her2neu expression and prognosis of ovarian high grade serous carcinoma Materials: This cross-sectional study will be done on 54 specimens of ovarian primary high grade serous carcinoma cases who attended to Oncology Centre, Mansoura University, Mansoura, Egypt since 2012 to the end of 5 years follow up of the last patient The cases will be chosen randomly. Methods: All clinicopathological data of these cases will be collected such as Tumor size, LN metastases (N), metastasis (M), ascites, residual tumor, peritoneal deposits, recurrence, TNM staging & (FIGO) staging system. Prepare hematoxylin & eosin slides to diagnose and assess other histopathological parameters such as histological type Immunohistochemistry: Sections 4μm thickness from newly formed tissue microarray blocks will be cut on coated slides then immunohistochemical staining using antibody against EGFR& Her2neu will be done. Statistical analysis: SPSS software version 20 (SPSS Inc., Chicago, IL) will be used for analysis. For nominal variables, proportions and X2 tests will be applied, whereas for interval variables means, standard deviations (SD), and T test and ANOVA tests will be applied where appropriate. Kaplan-Meier method will be used for survival analysis. Chi-square test was used to estimate the relation between qualitative variables. Mann-Whitney test (non-parametric t test) was used for not normally distributed quantitative data, for comparison between two groups while, comparison between three groups was done using Kruskal-Wallis test (non-parametric ANOVA).
Official Title
-----------------
Prognostic Value of Her2neu and EGFR in Primary Ovarian High Grade Serous Carcinoma.
Conditions
-----------------
Ovarian Cancer
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with primary ovarian cancer Exclusion Criteria: patients with secondary ovarian cancer
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EGFR& Her2neu expression to the grade of ovarian serous carcinoma | EGFR& Her2neu expression in primary ovarian high grade serous carcinoma | 2 years |
| EGFR& Her2neu expression in primary ovarian serous carcinoma to prognosis | Expression of EGFR & Her2neu in primary ovarian cancer to cancer free period | 5 years |
|
|||||
NCT01362283
|
Epidemiologic Study to Evaluate the Proportion of Cardiovascular Disease Risk Factors in Korean Hypertensive Patients
|
The purpose of this study is investigating the proportion of Cardiovascular disease risk factors of hypertensive patients.
|
Primary endpoint: To evaluate the Proportion of patients with Cardiovascular disease high risk factors~Secondary endpoint: To evaluate the Proportion of patients with Cardiovascular disease risk factors, To evaluate the Proportion of patients with Cardiovascular disease, To evaluate Target blood pressure achievement rate according to the proportion of Cardiovascular disease risks
|
A Multi-center, Observational, Cross-sectional Study to Evaluate CVD Risk Factors in Korean Hypertensive Patients
|
Hypertension
|
* Other: Blood Sampling
|
Inclusion Criteria:~Essential hypertensive patient no less than 18 yeas old~Patient who gave informed consent form~Exclusion Criteria:~Patient was diagnosed as secondary hypertension~Patient who have white-coat hypertension
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with cardiovascular disease high risk factors | Between patients with essential hypertension | 6years, average duration of hypertension |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with Cardiovascular disease risk factors | Between patients with essential hypertension | 6years, average duration of hypertension |
| Proportion of patients with Cardiovascular disease | Between patients with essential hypertension | 6years, average duration of hypertension |
| Target Blood Pressure achievement rate according to the proportion of Cardiovascular disease risks | Between patients with essential hypertension | 6years, average duration of hypertension |
|
Hypertension, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hypertension<br>Subject who meet eligible criteria | Other: Blood Sampling<br>* Blood sampling for Fasting Plasma Glucose, Hemoglobin A1C, Cholesterols, Blood Urea Nitrogen, Creatinine<br>* Other names: Blood sampling for cardiovascular disease risk;|
|
Epidemiologic Study to Evaluate the Proportion of Cardiovascular Disease Risk Factors in Korean Hypertensive Patients
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is investigating the proportion of Cardiovascular disease risk factors of hypertensive patients.
Detailed Description
-----------------
Primary endpoint: To evaluate the Proportion of patients with Cardiovascular disease high risk factors Secondary endpoint: To evaluate the Proportion of patients with Cardiovascular disease risk factors, To evaluate the Proportion of patients with Cardiovascular disease, To evaluate Target blood pressure achievement rate according to the proportion of Cardiovascular disease risks
Official Title
-----------------
A Multi-center, Observational, Cross-sectional Study to Evaluate CVD Risk Factors in Korean Hypertensive Patients
Conditions
-----------------
Hypertension
Intervention / Treatment
-----------------
* Other: Blood Sampling
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Essential hypertensive patient no less than 18 yeas old Patient who gave informed consent form Exclusion Criteria: Patient was diagnosed as secondary hypertension Patient who have white-coat hypertension
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hypertension<br>Subject who meet eligible criteria | Other: Blood Sampling<br>* Blood sampling for Fasting Plasma Glucose, Hemoglobin A1C, Cholesterols, Blood Urea Nitrogen, Creatinine<br>* Other names: Blood sampling for cardiovascular disease risk;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with cardiovascular disease high risk factors | Between patients with essential hypertension | 6years, average duration of hypertension |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with Cardiovascular disease risk factors | Between patients with essential hypertension | 6years, average duration of hypertension |
| Proportion of patients with Cardiovascular disease | Between patients with essential hypertension | 6years, average duration of hypertension |
| Target Blood Pressure achievement rate according to the proportion of Cardiovascular disease risks | Between patients with essential hypertension | 6years, average duration of hypertension |
|
||
NCT03312023
|
Ledipasvir/Sofosbuvir for Hepatitis B Virus Infection
|
The goals of therapy against chronic hepatitis B are to decrease the morbidity and mortality related to chronic HBV infection. Currently available antiviral therapy can suppress viral replication but only a small proportion attain functional cure, which is defined as HBV surface antigen-to-antibody seroconversion. Hepatitis B surface antigen (HBsAg) is a marker of persistent hepatitis B infection.~It has been observed that patients who had both hepatitis B and hepatitis C, and who were treated for their hepatitis C with 12 weeks of ledipasvir/sofosbuvir for had a decline in HBsAg levels. This study hypothesizes that a similar decrease would be seen in mono-infected hepatitis B subjects over the course of 12 weeks treatment with ledipasvir/sofosbuvir.
|
A Phase II Open-Label Study of Ledipasvir/Sofosbuvir for 12 Weeks in Subjects With Hepatitis B Virus Infection
|
Hepatitis B
|
* Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]
* Drug: Sofosbuvir 400 MG [Sovaldi]
* Drug: Ledipasvir 90 MG
|
INCLUSION CRITERIA~Participants in Groups A, C & D (Chronic HBV, low replicative state not requiring treatment):~Provision of signed and dated informed consent form~Stated willingness to comply with all study procedures and availability for the duration of the study~Male or female, aged 18 or older at screening~Diagnosed with chronic hepatitis B infection defined as one of the following:~HBsAg or HBV DNA positivity for at least 6 months~Medical records indicating a chronic HBV infection~HBeAg negative at screening~HBV DNA > lower level of quantitation (LLOQ)~Quantitative HBsAg at least 10 IU/mL at screening~Ability to take oral medication and be willing to adhere to the twelve week study drug regimen~For females of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 30 days after the end of study drug administration~For males of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 14 days after the end of study drug administration~Ability to communicate effectively with the study investigator and key staff~Medical management provided by a primary care provider~Ability to store medications at a room temperature of less than 86 degrees Fahrenheit~Not on antiviral therapy or requiring treatment for HBV during screening~Participants in Group B (Chronic HBV, virally suppressed):~Provision of signed and dated informed consent form~Stated willingness to comply with all study procedures and availability for the duration of the study~Male or female, aged 18 or older at screening~Diagnosed with chronic hepatitis B infection defined as one of the following:~HBsAg or HBV DNA positivity for at least 6 months~Medical records indicating a chronic HBV infection~Receiving oral anti-HBV medications (either tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir, or a combination of no more than 2 of these agents) for at least three months prior to enrollment~HBV DNA ˂ lower level of quantitation (LLOQ) at screening and for at least three months prior~Quantitative HBsAg at least 10 IU/mL at screening~Ability to take oral medication and be willing to adhere to the twelve week study drug regimen~For females of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 30 days after the end of study drug administration~For males of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 14 days after the end of study drug administration~Ability to communicate effectively with the study investigator and key staff~Medical management provided by a primary care provider~Ability to store medications at a room temperature of less than 86 degrees Fahrenheit~EXCLUSION CRITERIA~Coinfection with hepatitis C, hepatitis D or human immunodeficiency virus (HIV)~Pregnancy or lactation~Known allergic reactions to sofosbuvir or ledipasvir~Treatment with another investigational drug or other intervention within three months~Evidence of cirrhosis or hepatic decompensation such as:~Platelets less than 100,000 /mm3~Albumin less than 3.5 g/dL~INR greater than 1.7 or Prothrombin time of 1.5 times the upper limit of normal (ULN)~Total bilirubin of 1.5 times the upper limit of normal~FibroTest (or FibroSure®) of 0.75 or greater~Abnormal hematological and biochemical parameters at screening including:~White blood cell count less than 2500 cells/uL~Absolute neutrophil count (ANC) less than 1,000 cells/mm3 (less than 750 mm3 for African or African-American subjects)~Hemoglobin less than 12 g/dL for males, less than 11 g/dL for females~AST or ALT of two times the upper limit of normal~Estimated GFR less than 50 mL/min~Glycosylated hemoglobin (HbA1c) greater than 8.5%~Current or prior history of any of the following:~Immunodeficiency disorders or autoimmune disease (e.g. Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel diseases, sarcoidosis, psoriasis of greater than mild severity)~Severe pulmonary disorders, significant cardiac diseases~Gastrointestinal disorder with post-operative condition that could interfere with the absorption of the study drugs~Significant psychiatric illness that in the judgment of the Investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent~Any malignancy diagnosed within 5 years (not including recent localized treatment of squamous or non-invasive basal cell skin cancer; cervical carcinoma in situ appropriately treated prior to screening)~Solid organ transplantation~Poor venous access~Screening ECG with clinically significant findings~Evidence of HCC (e.g., α fetoprotein > 50ng/mL or radiologic evidence)~Clinically significant illicit drug or alcohol abuse within 12 months of screening. Subjects on methadone maintenance treatment or prescribed opioid may be included.~Use of amiodarone within 90 days of enrollment; or carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, rifapentine, St. John's wort, rosuvastatin, or interferon within 30 days of enrollment or expected use of these prohibited drugs during study participation. Use of or expected need of proton-pump inhibitors more than 20 mg omeprazole equivalent or H2 receptor antagonist more than 40 mg famotidine BID equivalent within 7 days of enrollment.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label Study, multi-arm
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Serum Hepatitis B Surface Antigen (HBsAg as Measured in log10 IU/mL) Level as an Indicator of Antiviral Activity of Ledipasvir and/or Sofosbuvir in Subjects With Chronic Hepatitis B From Baseline to End of 12 Weeks Treatment. | Subjects with chronic hepatitis B will be give 12 weeks of ledipasvir and/or sofosbuvir and their HBsAg will be measured at baseline, on each visits during therapy, and at end of therapy (week 12). The change (decline) in HBsAg from baseline to end of the 12 week treatment will be compared. | 12 weeks |
| Incidence of Adverse Events Leading to Permanent Discontinuation of Ledipasvir and/or Sofosbuvir Treatment in Subjects With Chronic Hepatitis B Infection. | Number of subjects who discontinued study drug due to adverse event | 12 Weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Serum Hepatitis B Virus DNA Levels (HBV DNA as Measured in IU/mL) With Treatment of Ledipasvir and/or Sofosbuvir From Baseline to End of 12 Weeks of Treatment in Subjects With Chronic Hepatitis B Infection. | Subjects with chronic hepatitis B will be give 12 weeks of ledipasvir and/or sofosbuvir and their serum hepatitis B DNA levels (HBV DNA) will be measured at baseline, on each visits during therapy, and at end of therapy (week 12). The change in HBV DNA levels from baseline to end of the 12 week treatment will be compared.~Note: Group B (virally suppressed HBV subjects) - all had HBV DNA below the limit of detection; Hence, mean change was 0. | 12 weeks |
|
Hepatitis B, HBsAg, Ledipasvir/Sofosbuvir, Hepatitis B treatment
|
Sofosbuvir, Ledipasvir, sofosbuvir drug combination, Ledipasvir, Antiviral Agents, Anti-Infective Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A (LDV/SOF for low replicative HBV)<br>12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state. | Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]<br>* 1 pill once daily for 12 weeks for Group A<br>* Other names: Harvoni;|
| Experimental: Group B (LDV/SOF for viral suppressed HBV)<br>12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B, virally suppressed. | Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]<br>* 1 pill once daily for 12 weeks for Group A<br>* Other names: Harvoni;|
| Experimental: Group C (SOF for low replicative HBV)<br>12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state.~Randomized 1:1 with Group D. | Drug: Sofosbuvir 400 MG [Sovaldi]<br>* 1 pill once daily for 12 weeks for Group C<br>* Other names: GS-7977;|
| Experimental: Group D (LDV for low replicative HBV)<br>12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state.~Randomized 1:1 with Group C. | Drug: Ledipasvir 90 MG<br>* 1 pill once daily for 12 weeks for Group D<br>* Other names: GS-5885;|
|
Ledipasvir/Sofosbuvir for Hepatitis B Virus Infection
Study Overview
=================
Brief Summary
-----------------
The goals of therapy against chronic hepatitis B are to decrease the morbidity and mortality related to chronic HBV infection. Currently available antiviral therapy can suppress viral replication but only a small proportion attain functional cure, which is defined as HBV surface antigen-to-antibody seroconversion. Hepatitis B surface antigen (HBsAg) is a marker of persistent hepatitis B infection. It has been observed that patients who had both hepatitis B and hepatitis C, and who were treated for their hepatitis C with 12 weeks of ledipasvir/sofosbuvir for had a decline in HBsAg levels. This study hypothesizes that a similar decrease would be seen in mono-infected hepatitis B subjects over the course of 12 weeks treatment with ledipasvir/sofosbuvir.
Official Title
-----------------
A Phase II Open-Label Study of Ledipasvir/Sofosbuvir for 12 Weeks in Subjects With Hepatitis B Virus Infection
Conditions
-----------------
Hepatitis B
Intervention / Treatment
-----------------
* Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]
* Drug: Sofosbuvir 400 MG [Sovaldi]
* Drug: Ledipasvir 90 MG
Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA Participants in Groups A, C & D (Chronic HBV, low replicative state not requiring treatment): Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged 18 or older at screening Diagnosed with chronic hepatitis B infection defined as one of the following: HBsAg or HBV DNA positivity for at least 6 months Medical records indicating a chronic HBV infection HBeAg negative at screening HBV DNA > lower level of quantitation (LLOQ) Quantitative HBsAg at least 10 IU/mL at screening Ability to take oral medication and be willing to adhere to the twelve week study drug regimen For females of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 30 days after the end of study drug administration For males of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 14 days after the end of study drug administration Ability to communicate effectively with the study investigator and key staff Medical management provided by a primary care provider Ability to store medications at a room temperature of less than 86 degrees Fahrenheit Not on antiviral therapy or requiring treatment for HBV during screening Participants in Group B (Chronic HBV, virally suppressed): Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged 18 or older at screening Diagnosed with chronic hepatitis B infection defined as one of the following: HBsAg or HBV DNA positivity for at least 6 months Medical records indicating a chronic HBV infection Receiving oral anti-HBV medications (either tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir, or a combination of no more than 2 of these agents) for at least three months prior to enrollment HBV DNA ˂ lower level of quantitation (LLOQ) at screening and for at least three months prior Quantitative HBsAg at least 10 IU/mL at screening Ability to take oral medication and be willing to adhere to the twelve week study drug regimen For females of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 30 days after the end of study drug administration For males of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 14 days after the end of study drug administration Ability to communicate effectively with the study investigator and key staff Medical management provided by a primary care provider Ability to store medications at a room temperature of less than 86 degrees Fahrenheit EXCLUSION CRITERIA Coinfection with hepatitis C, hepatitis D or human immunodeficiency virus (HIV) Pregnancy or lactation Known allergic reactions to sofosbuvir or ledipasvir Treatment with another investigational drug or other intervention within three months Evidence of cirrhosis or hepatic decompensation such as: Platelets less than 100,000 /mm3 Albumin less than 3.5 g/dL INR greater than 1.7 or Prothrombin time of 1.5 times the upper limit of normal (ULN) Total bilirubin of 1.5 times the upper limit of normal FibroTest (or FibroSure®) of 0.75 or greater Abnormal hematological and biochemical parameters at screening including: White blood cell count less than 2500 cells/uL Absolute neutrophil count (ANC) less than 1,000 cells/mm3 (less than 750 mm3 for African or African-American subjects) Hemoglobin less than 12 g/dL for males, less than 11 g/dL for females AST or ALT of two times the upper limit of normal Estimated GFR less than 50 mL/min Glycosylated hemoglobin (HbA1c) greater than 8.5% Current or prior history of any of the following: Immunodeficiency disorders or autoimmune disease (e.g. Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel diseases, sarcoidosis, psoriasis of greater than mild severity) Severe pulmonary disorders, significant cardiac diseases Gastrointestinal disorder with post-operative condition that could interfere with the absorption of the study drugs Significant psychiatric illness that in the judgment of the Investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent Any malignancy diagnosed within 5 years (not including recent localized treatment of squamous or non-invasive basal cell skin cancer; cervical carcinoma in situ appropriately treated prior to screening) Solid organ transplantation Poor venous access Screening ECG with clinically significant findings Evidence of HCC (e.g., α fetoprotein > 50ng/mL or radiologic evidence) Clinically significant illicit drug or alcohol abuse within 12 months of screening. Subjects on methadone maintenance treatment or prescribed opioid may be included. Use of amiodarone within 90 days of enrollment; or carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, rifapentine, St. John's wort, rosuvastatin, or interferon within 30 days of enrollment or expected use of these prohibited drugs during study participation. Use of or expected need of proton-pump inhibitors more than 20 mg omeprazole equivalent or H2 receptor antagonist more than 40 mg famotidine BID equivalent within 7 days of enrollment.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label Study, multi-arm
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A (LDV/SOF for low replicative HBV)<br>12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state. | Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]<br>* 1 pill once daily for 12 weeks for Group A<br>* Other names: Harvoni;|
| Experimental: Group B (LDV/SOF for viral suppressed HBV)<br>12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B, virally suppressed. | Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]<br>* 1 pill once daily for 12 weeks for Group A<br>* Other names: Harvoni;|
| Experimental: Group C (SOF for low replicative HBV)<br>12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state. Randomized 1:1 with Group D. | Drug: Sofosbuvir 400 MG [Sovaldi]<br>* 1 pill once daily for 12 weeks for Group C<br>* Other names: GS-7977;|
| Experimental: Group D (LDV for low replicative HBV)<br>12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state. Randomized 1:1 with Group C. | Drug: Ledipasvir 90 MG<br>* 1 pill once daily for 12 weeks for Group D<br>* Other names: GS-5885;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Serum Hepatitis B Surface Antigen (HBsAg as Measured in log10 IU/mL) Level as an Indicator of Antiviral Activity of Ledipasvir and/or Sofosbuvir in Subjects With Chronic Hepatitis B From Baseline to End of 12 Weeks Treatment. | Subjects with chronic hepatitis B will be give 12 weeks of ledipasvir and/or sofosbuvir and their HBsAg will be measured at baseline, on each visits during therapy, and at end of therapy (week 12). The change (decline) in HBsAg from baseline to end of the 12 week treatment will be compared. | 12 weeks |
| Incidence of Adverse Events Leading to Permanent Discontinuation of Ledipasvir and/or Sofosbuvir Treatment in Subjects With Chronic Hepatitis B Infection. | Number of subjects who discontinued study drug due to adverse event | 12 Weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Serum Hepatitis B Virus DNA Levels (HBV DNA as Measured in IU/mL) With Treatment of Ledipasvir and/or Sofosbuvir From Baseline to End of 12 Weeks of Treatment in Subjects With Chronic Hepatitis B Infection. | Subjects with chronic hepatitis B will be give 12 weeks of ledipasvir and/or sofosbuvir and their serum hepatitis B DNA levels (HBV DNA) will be measured at baseline, on each visits during therapy, and at end of therapy (week 12). The change in HBV DNA levels from baseline to end of the 12 week treatment will be compared. Note: Group B (virally suppressed HBV subjects) - all had HBV DNA below the limit of detection; Hence, mean change was 0. | 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis B, HBsAg, Ledipasvir/Sofosbuvir, Hepatitis B treatment
|
|
NCT03721237
|
Esophageal Balloon Calibration in Assisted Ventilation Mode
|
Esophageal balloon calibration (EBC) has been proposed during controlled mechanical ventilation in intubated patients in order to optimize esophageal pressure (Pes) signal. Actually, at our knowledge, no data exist about EBC during assisted ventilatory modes such as Pressure Support Ventilation (PSV). The primary endpoint of the present investigation is to assess the feasibility of EBC during PSV and PSV plus Sigh.
|
Assisted ventilatory modes, nowadays, have been proved to reduce complications related to controlled mechanical ventilation. With these modes, ventilatory cycling is under the patient's control to an extent depending on the type of ventilatory modality.~Sigh improves oxygenation and lung mechanics during pressure control ventilation and pressure support ventilation (PSV) in patients with acute respiratory distress syndrome.~In order to better quantify the effects of both PSV and PSV plus Sigh on respiratory mechanics, the esophageal pressure monitoring could be helpful. However, esophageal pressure (Pes) assessment requires esophageal ballon calibration (EBC) as demonstrated in intubated patients under controlled mechanical ventilation.~At our knowledge, no data exist about EBC during assisted ventilatory modes. The primary aim of the present study is to evaluate the effects of PSV and PSV plus Sigh ventilation on esophageal balloon best volume in patients admitted to the intensive care unit for acute respiratory failure.~.
|
Esophageal Balloon Calibration During Assisted Ventilation Modes and Sigh: a Feasibility Study
|
Respiratory Failure, Mechanical Ventilation Pressure High
|
* Other: EBC-assisted
|
Inclusion Criteria:~patients older than 18 years;~undergoing mechanical ventilation for more than 24 hours (in volume-controlled mode) and with readiness to run assisted ventilation;~Exclusion Criteria:~severe COPD with air trapping clinical suspicion;~hemodynamic instability requiring inotropic or vasopressor support;~any contraindications to esophageal catheter positioning
|
18 Years
| null |
All
|
No
|
Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of ventilatory mode on calibrated esophageal ballon best volume | Evaluation of changes of esophageal balloon best volume (ml) induced by ventilatory modes | Over 120 minutes in PSV |
| Number of patients in who esophageal balloon calibration is performed (feasibility) during PSV + Sigh | Evaluate the feasibility of esophageal catheter calibration during assisted ventilation modes during PSV + Sigh | Over 30 minutes in PSV + Sigh |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of respiratory mechanics indices in PSV | lung, chest wall and respiratory system elastance (cmH2O/l) | over 30 minutes in PSV |
| Changes of respiratory mechanics indices in PSV + sigh | lung, chest wall and respiratory system elastance (cmH2O/l) | over 30 minutes in PSV + Sigh |
| Gas exchange | PaCO2, Ph and blood oxygenation (PaO2) will be obtained performing ABGs. | over 30 minutes during each trial |
|
Esophageal catheter calibration, Assisted mechanical ventilation
|
Respiratory Insufficiency, Respiration Disorders, Respiratory Tract Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBC-assisted<br>A nasogastric tube, equipped with esophageal and gastric balloons, will be inserted in each patient enrolled in the study. After definitive catheter positioning has been obtained, Esophageal ballon calibration will be run in volume-controlled ventilation, pressure support ventilation and sigh + pressure support ventilation. | Other: EBC-assisted<br>* After definitive catheter positioning, esophageal balloon calibration will be performed in:~volume-controlled mode with tidal volume set to obtain 6-8 lm/kg of ideal body weight (reference),~pressure support ventilation (PSV) with support set to obtain a tidal volume ranging between 6-8 ml/kg of ideal body weight at equal PEEP of volume control mode (PSV baseline);~PSV + sigh ventilation (sigh setting: total inspiratory pressure equal to 35 cmH2O at a rate of 1/ minute; inspiratory time equal to 4 seconds).<br>|
|
Esophageal Balloon Calibration in Assisted Ventilation Mode
Study Overview
=================
Brief Summary
-----------------
Esophageal balloon calibration (EBC) has been proposed during controlled mechanical ventilation in intubated patients in order to optimize esophageal pressure (Pes) signal. Actually, at our knowledge, no data exist about EBC during assisted ventilatory modes such as Pressure Support Ventilation (PSV). The primary endpoint of the present investigation is to assess the feasibility of EBC during PSV and PSV plus Sigh.
Detailed Description
-----------------
Assisted ventilatory modes, nowadays, have been proved to reduce complications related to controlled mechanical ventilation. With these modes, ventilatory cycling is under the patient's control to an extent depending on the type of ventilatory modality. Sigh improves oxygenation and lung mechanics during pressure control ventilation and pressure support ventilation (PSV) in patients with acute respiratory distress syndrome. In order to better quantify the effects of both PSV and PSV plus Sigh on respiratory mechanics, the esophageal pressure monitoring could be helpful. However, esophageal pressure (Pes) assessment requires esophageal ballon calibration (EBC) as demonstrated in intubated patients under controlled mechanical ventilation. At our knowledge, no data exist about EBC during assisted ventilatory modes. The primary aim of the present study is to evaluate the effects of PSV and PSV plus Sigh ventilation on esophageal balloon best volume in patients admitted to the intensive care unit for acute respiratory failure. .
Official Title
-----------------
Esophageal Balloon Calibration During Assisted Ventilation Modes and Sigh: a Feasibility Study
Conditions
-----------------
Respiratory Failure, Mechanical Ventilation Pressure High
Intervention / Treatment
-----------------
* Other: EBC-assisted
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients older than 18 years; undergoing mechanical ventilation for more than 24 hours (in volume-controlled mode) and with readiness to run assisted ventilation; Exclusion Criteria: severe COPD with air trapping clinical suspicion; hemodynamic instability requiring inotropic or vasopressor support; any contraindications to esophageal catheter positioning
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBC-assisted<br>A nasogastric tube, equipped with esophageal and gastric balloons, will be inserted in each patient enrolled in the study. After definitive catheter positioning has been obtained, Esophageal ballon calibration will be run in volume-controlled ventilation, pressure support ventilation and sigh + pressure support ventilation. | Other: EBC-assisted<br>* After definitive catheter positioning, esophageal balloon calibration will be performed in: volume-controlled mode with tidal volume set to obtain 6-8 lm/kg of ideal body weight (reference), pressure support ventilation (PSV) with support set to obtain a tidal volume ranging between 6-8 ml/kg of ideal body weight at equal PEEP of volume control mode (PSV baseline); PSV + sigh ventilation (sigh setting: total inspiratory pressure equal to 35 cmH2O at a rate of 1/ minute; inspiratory time equal to 4 seconds).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of ventilatory mode on calibrated esophageal ballon best volume | Evaluation of changes of esophageal balloon best volume (ml) induced by ventilatory modes | Over 120 minutes in PSV |
| Number of patients in who esophageal balloon calibration is performed (feasibility) during PSV + Sigh | Evaluate the feasibility of esophageal catheter calibration during assisted ventilation modes during PSV + Sigh | Over 30 minutes in PSV + Sigh |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of respiratory mechanics indices in PSV | lung, chest wall and respiratory system elastance (cmH2O/l) | over 30 minutes in PSV |
| Changes of respiratory mechanics indices in PSV + sigh | lung, chest wall and respiratory system elastance (cmH2O/l) | over 30 minutes in PSV + Sigh |
| Gas exchange | PaCO2, Ph and blood oxygenation (PaO2) will be obtained performing ABGs. | over 30 minutes during each trial |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Esophageal catheter calibration, Assisted mechanical ventilation
|
NCT03081052
|
Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
|
1. to conduct a clinical investigation to determine if inhaled epoprostenol (Veletri®, iEPO) and inhaled nitric oxide (iNO) will have similar impact on outcomes in adult patients undergoing durable LVAD placement, heart transplantation, or lung transplantation 2. to conduct a cost-capture analysis on the expense each drug incurs per patient.
|
In adult cardiothoracic surgical patients, iNO is used to treat precapillary pulmonary hypertension (PH), right-sided heart failure (RHF), and ventilation-to-perfusion (V:Q) mismatch. Adult patients who undergo durable LVAD implantation (e.g. Heartware®, Heartmate 2®, or Heartmate 3®), cardiac transplantation for HFrEF, or those that have endured lung transplantation as a result of end-stage lung disease, compose the largest subpopulation which receives iPVD therapy at Duke University Hospital. iEPO may display an equivalent efficacy profile to iNO for pulmonary vasodilation and oxygenation and have a similar impact on clinical outcomes.~Subjects undergoing LVAD placement or heart transplantation (N=224) or lung transplantation (N=200) will be prospectively enrolled over a three-year period (one-year for follow-up). Patients will be randomly assigned 1:1 according to stratified randomization blocking either iNO or iEPO. Additional study procedures will involve data collection, blood, and tissue sampling.
|
Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
|
Heart Transplant Surgery, Lung Transplant Surgery
|
* Drug: iNO
* Drug: iEPO
|
Inclusion Criteria:~Heart transplantation~LVAD placement~Lung Transplantation~Exclusion Criteria:~Combined Organ Transplantation~Age < 18 years old~Pregnancy~Known allergy to prostaglandin (rare)~Refusal of blood products due to personal or religious preference~Subject is enrolled in another study protocol, which does not allow randomization of PVD therapy~Heart transplant or durable LVAD recipients with adult congenital heart disease (CHD)~o Caveat: Does NOT meet exclusion criteria if the scheduled heart transplant or LVAD implantation is due to heart failure from a previous heart transplantation related to CHD, performed more than 90 days previous to the date of trial enrollment~Heart transplant recipients diagnosed with Arrythmogenic Right Ventricular Cardiomyopathy~Heart transplant recipients diagnosed with Acute Cardiac Allograft Rejection after a previous heart transplantation.~Heart transplant or durable LVAD recipients with preoperative RVAD for right heart failure~Patient is scheduled to undergo lung transplantation but has undergone heart transplantation in the previous 90 days~Patient is scheduled to undergo durable LVAD implantation but has undergone heart transplantation in the previous 90 days~Patient is scheduled to undergo heart transplantation but has undergone lung transplantation in the previous 90 days~Patients with preoperative Venovenous ECMO as a bridge to lung transplantation~Heart transplant or durable LVAD recipients with preoperative RVAD for right heart failure
|
18 Years
| null |
All
|
No
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3 Primary Graft Dysfunction (PGD) for Lung Transplant Subjects | This is defined by the International Society of Heart and Lung Transplantation (ISHLT) as severe hypoxemia with a PaO2-to-FiO2 ratio < 200 or the presence of venovenous extracorporeal membrane oxygenation (VV ECMO) at a time-point within the first 72 hours after lung transplantation. | Up to 72 hours |
| Number of Participants With Moderate or Severe RV Failure for the LVAD Implantation Subjects and Severe RV Failure for Heart Transplantation Subjects | This is defined by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score of moderate or severe right-heart failure for LVADS, and by the incidence of an RVAD placement or ECMO for RHF for heart transplants. | up to approximately 21 days after LVAD placement, up to approximately 30 days after heart transplantation |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Postoperative Mechanical Ventilation | Length of time from intubation until patient is extubated | up to approximately 90 days after index surgery |
| Per Patient Inhaled Pulmonary Vasodilator (iPVD) Cost | Data reflects a per patient cost in dollars that has been scaled to a unit of measure relative to the cost per hour of drug and multiplied by the duration of iPVD administration. In our study, iNO cost 7 times that of iEPO per hour, hence for each patient this outcome value is the duration of iPVD administration multiplied by 7 if a patient is randomized to iNO or multiplied by 1 if randomized to iEPO. | up to approximately 30 days after index surgery |
| Length of ICU Stay | Length of time from ICU admission from surgery until ICU discharge | up to approximately 90 days after index surgery |
| Length of Hospital Stay | Length of time from surgery to hospital discharge | up to approximately 1 year after index surgery |
| Number of Participants With Acute Kidney Injury | defined by Modified KDIGO-AKI definition:~Increase in Serum Creatinine (Cr) by ≥0.3mg/dL within 48 hours; or~Increase in Cr to ≥1.5 times baseline~Urine output is not included as urine could be under-captured after Foley catheter removal | up to approximately 14 days |
| Number of Participants With In-hospital Mortality | Death that occurs during the hospital stay | up to approximately 1 year after index surgery |
| Number of Participants With Post-operative Mortality Within 30 Days | From the day of surgery to 30 days postoperatively. | up to approximately 30 days after index surgery |
| Number of Participants With Post-operative Mortality Within 90 Days | From the day of surgery to 90 days after index surgery | up to approximately 90 days after index surgery |
|
Heart and Lung transplantation surgery, Pulmonary vasodilation therapy
|
Nitric Oxide, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Asthmatic Agents, Respiratory System Agents, Free Radical Scavengers, Antioxidants, Molecular Mechanisms of Pharmacological Action, Neurotransmitter Agents, Endothelium-Dependent Relaxing Factors, Vasodilator Agents, Gasotransmitters, Protective Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lung transplant with iNO<br> | Drug: iNO<br>* Subject will receive inhaled Nitric Oxide in this intervention<br>* Other names: Inhaled Nitric Oxide;|
| Active Comparator: Lung transplant with iEPO<br> | Drug: iEPO<br>* Subject will receive inhaled Epoprostrenol in this intervention<br>* Other names: Inhaled Epoprostrenol;|
| Active Comparator: Heart transplant & LVAD implantation with iNO<br> | Drug: iNO<br>* Subject will receive inhaled Nitric Oxide in this intervention<br>* Other names: Inhaled Nitric Oxide;|
| Active Comparator: Heart transplant & LVAD implantation with iEPO<br> | Drug: iEPO<br>* Subject will receive inhaled Epoprostrenol in this intervention<br>* Other names: Inhaled Epoprostrenol;|
|
Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
Study Overview
=================
Brief Summary
-----------------
1. to conduct a clinical investigation to determine if inhaled epoprostenol (Veletri®, iEPO) and inhaled nitric oxide (iNO) will have similar impact on outcomes in adult patients undergoing durable LVAD placement, heart transplantation, or lung transplantation 2. to conduct a cost-capture analysis on the expense each drug incurs per patient.
Detailed Description
-----------------
In adult cardiothoracic surgical patients, iNO is used to treat precapillary pulmonary hypertension (PH), right-sided heart failure (RHF), and ventilation-to-perfusion (V:Q) mismatch. Adult patients who undergo durable LVAD implantation (e.g. Heartware®, Heartmate 2®, or Heartmate 3®), cardiac transplantation for HFrEF, or those that have endured lung transplantation as a result of end-stage lung disease, compose the largest subpopulation which receives iPVD therapy at Duke University Hospital. iEPO may display an equivalent efficacy profile to iNO for pulmonary vasodilation and oxygenation and have a similar impact on clinical outcomes. Subjects undergoing LVAD placement or heart transplantation (N=224) or lung transplantation (N=200) will be prospectively enrolled over a three-year period (one-year for follow-up). Patients will be randomly assigned 1:1 according to stratified randomization blocking either iNO or iEPO. Additional study procedures will involve data collection, blood, and tissue sampling.
Official Title
-----------------
Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
Conditions
-----------------
Heart Transplant Surgery, Lung Transplant Surgery
Intervention / Treatment
-----------------
* Drug: iNO
* Drug: iEPO
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Heart transplantation LVAD placement Lung Transplantation Exclusion Criteria: Combined Organ Transplantation Age < 18 years old Pregnancy Known allergy to prostaglandin (rare) Refusal of blood products due to personal or religious preference Subject is enrolled in another study protocol, which does not allow randomization of PVD therapy Heart transplant or durable LVAD recipients with adult congenital heart disease (CHD) o Caveat: Does NOT meet exclusion criteria if the scheduled heart transplant or LVAD implantation is due to heart failure from a previous heart transplantation related to CHD, performed more than 90 days previous to the date of trial enrollment Heart transplant recipients diagnosed with Arrythmogenic Right Ventricular Cardiomyopathy Heart transplant recipients diagnosed with Acute Cardiac Allograft Rejection after a previous heart transplantation. Heart transplant or durable LVAD recipients with preoperative RVAD for right heart failure Patient is scheduled to undergo lung transplantation but has undergone heart transplantation in the previous 90 days Patient is scheduled to undergo durable LVAD implantation but has undergone heart transplantation in the previous 90 days Patient is scheduled to undergo heart transplantation but has undergone lung transplantation in the previous 90 days Patients with preoperative Venovenous ECMO as a bridge to lung transplantation Heart transplant or durable LVAD recipients with preoperative RVAD for right heart failure
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lung transplant with iNO<br> | Drug: iNO<br>* Subject will receive inhaled Nitric Oxide in this intervention<br>* Other names: Inhaled Nitric Oxide;|
| Active Comparator: Lung transplant with iEPO<br> | Drug: iEPO<br>* Subject will receive inhaled Epoprostrenol in this intervention<br>* Other names: Inhaled Epoprostrenol;|
| Active Comparator: Heart transplant & LVAD implantation with iNO<br> | Drug: iNO<br>* Subject will receive inhaled Nitric Oxide in this intervention<br>* Other names: Inhaled Nitric Oxide;|
| Active Comparator: Heart transplant & LVAD implantation with iEPO<br> | Drug: iEPO<br>* Subject will receive inhaled Epoprostrenol in this intervention<br>* Other names: Inhaled Epoprostrenol;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3 Primary Graft Dysfunction (PGD) for Lung Transplant Subjects | This is defined by the International Society of Heart and Lung Transplantation (ISHLT) as severe hypoxemia with a PaO2-to-FiO2 ratio < 200 or the presence of venovenous extracorporeal membrane oxygenation (VV ECMO) at a time-point within the first 72 hours after lung transplantation. | Up to 72 hours |
| Number of Participants With Moderate or Severe RV Failure for the LVAD Implantation Subjects and Severe RV Failure for Heart Transplantation Subjects | This is defined by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score of moderate or severe right-heart failure for LVADS, and by the incidence of an RVAD placement or ECMO for RHF for heart transplants. | up to approximately 21 days after LVAD placement, up to approximately 30 days after heart transplantation |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Postoperative Mechanical Ventilation | Length of time from intubation until patient is extubated | up to approximately 90 days after index surgery |
| Per Patient Inhaled Pulmonary Vasodilator (iPVD) Cost | Data reflects a per patient cost in dollars that has been scaled to a unit of measure relative to the cost per hour of drug and multiplied by the duration of iPVD administration. In our study, iNO cost 7 times that of iEPO per hour, hence for each patient this outcome value is the duration of iPVD administration multiplied by 7 if a patient is randomized to iNO or multiplied by 1 if randomized to iEPO. | up to approximately 30 days after index surgery |
| Length of ICU Stay | Length of time from ICU admission from surgery until ICU discharge | up to approximately 90 days after index surgery |
| Length of Hospital Stay | Length of time from surgery to hospital discharge | up to approximately 1 year after index surgery |
| Number of Participants With Acute Kidney Injury | defined by Modified KDIGO-AKI definition: Increase in Serum Creatinine (Cr) by ≥0.3mg/dL within 48 hours; or Increase in Cr to ≥1.5 times baseline Urine output is not included as urine could be under-captured after Foley catheter removal | up to approximately 14 days |
| Number of Participants With In-hospital Mortality | Death that occurs during the hospital stay | up to approximately 1 year after index surgery |
| Number of Participants With Post-operative Mortality Within 30 Days | From the day of surgery to 30 days postoperatively. | up to approximately 30 days after index surgery |
| Number of Participants With Post-operative Mortality Within 90 Days | From the day of surgery to 90 days after index surgery | up to approximately 90 days after index surgery |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heart and Lung transplantation surgery, Pulmonary vasodilation therapy
|
NCT05329194
|
Effectiveness and Safety Study of Tezepelumab in Adults & Adolescent Participants With Severe Asthma in the United States
|
To asses effectiveness and safety of tezepelumab in adult and adolescent participants with severe asthma including several under-studied populations in the United States.
|
This is a multicenter, single-arm, open-label, Post-authorization, Phase 4 study to assess the effectiveness of tezepelumab in the United States (US) among a real-world population of adults and adolescent participants with asthma requiring medium-dose to high-dose inhaled corticosteroids (ICS), with additional controller(s) for at least 12 months with documented history of at least 2 asthma exacerbations during the year prior to enrolment. The total duration of the study for each participant will be approximately 56 weeks. Approximately 400 participants will be enrolled. Participants will receive tezepelumab via subcutaneous injection at the study site, over a 48-week treatment period. The study also includes a post-dosing follow-up period from Weeks 48 to 52.
|
A Multicenter, Single-arm, Open-label, Post-Authorization, Phase 4 Effectiveness and Safety Study of Tezepelumab in Adult and Adolescent Participants With Severe Asthma Including Several Under-Studied Populations in the United States (PASSAGE)
|
Asthma
|
* Drug: Tezepelumab
|
Inclusion Criteria:~Male or female participant must be 12 years of age or older, at the time of signing the informed consent form or assent.~Documented physician-diagnosed asthma for at least 12 months prior to enrollment and confirmed by the Investigator not to be due to alternative diagnoses.~Documented treatment with medium- to high dose ICS as per Global Initiative for Asthma (GINA) guidelines (GINA 2021) for at least 12 months prior to enrollment.~Use of additional asthma maintenance controller medication(s) in addition to ICS for at least 12 months prior to enrollment. The additional maintenance controller medication may be contained in a combination product (eg, ICS/ long-acting β-agonist (LABA)).~Documented history of at least 2 asthma exacerbations during the 12 months prior to enrollment.~Physician decision that participant is eligible for treatment with tezepelumab according to the approved United States product insert (USPI).~Currently receiving care from specialist physicians (eg, pulmonologists and/or allergists).~Provision of signed and dated written informed consent form.~Exclusion Criteria:~Any contraindication to tezepelumab as per the US approved product label or in the opinion of the Investigator.~Comorbid diagnosis of severe or very severe chronic obstructive pulmonary disease (COPD) per GOLD guidelines (GOLD 2021).~Use of biologics that are approved for the treatment of asthma within 4 months or 5 half- lives (whichever is longer) prior to enrollment.~Participation in an interventional clinical trial for asthma within 12 months prior to enrollment.~Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.
|
12 Years
|
130 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized asthma exacerbation rate (AAER) | Asthma exacerbation will be defined by worsening of asthma symptoms that leads to temporary bolus/burst of systemic corticosteroids for at least 3 consecutive days, or an emergency department (ED) or urgent care visit due to asthma that required systemic corticosteroid (SCS), and/or inpatient hospitalization (≥24 hours) due to asthma. The AAER is based on exacerbations reported by the investigator over 52 weeks.~The exacerbation rate will be compared between the 12 month period before (baseline period) and the 12 month period after initiation of tezepelumab (up to study Week 52 - study period). | Baseline period up to study Week 52 |
| Proportion of participants with asthma exacerbations | The proportion of participants with asthma exacerbations in the 12 month periods before (baseline period) and after initiation of tezepelumab (study period) (up to study Week 52 - study period) will be assessed. | Baseline period up to study Week 52 |
| Proportion of participants who completed the 52 -week study period with any reduction in total number of asthma exacerbations | The proportion of participants who completed the 52 -week study period following tezepelumab initiation with any reduction, at least 50% reduction, and 100% reduction in total number of asthma exacerbations will be assessed. | Baseline period up to study Week 52 |
| Cumulative asthma exacerbation days | The cumulative asthma exacerbation days over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first asthma exacerbation | The time to first exacerbation after initiation of tezepelumab will be assessed. | Week 0 to Week 52 |
| Rate of asthma exacerbations associated with hospitalizations | The rate of asthma exacerbations associated with hospitalization over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 |
| Rate of asthma exacerbations associated with emergency department /urgent care (ED/UC) visits | The rate of asthma exacerbations associated with ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 |
| Rate of asthma exacerbations associated with hospitalizations or ED/UC visits over | The rate of asthma exacerbations associated with hospitalizations or ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 |
| Proportion of participants with asthma exacerbations associated with hospitalizations or ED/UC visits | The proportion of participants with asthma exacerbations associated with hospitalizations or ED/UC visits in in the 12-month periods before (baseline period) and after initiation of tezepelumab (study period) (up to study Week 52) will be assessed. | Baseline period up to study Week 52 |
| Cumulative asthma exacerbation days associated with hospitalizations or ED/UC visits | The cumulative asthma exacerbation days associated with hospitalizations or ED/UC over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 |
| Pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) | Lung function (FEV1) will be measured pre-bronchodilator (pre-BD) by spirometry test. | Baseline (Week 0), Week 24, Week 52 |
| Change from baseline in pre-bronchodilator FEV1 | Change from baseline in pre-bronchodilator FEV1 will be assessed as lung function parameters after initiation of tezepelumab. | Baseline (Week 0), Week 24, Week 52 |
| Proportion of pre-BD FEV1 responders | Proportion of pre-BD FEV1 responders is defined as participants who achieve either at least 5% or 100 mL improvement from baseline. | Baseline (Week 0), Week 24, Week 52 |
| Asthma Control Questionnaire (ACQ-6) | The ACQ-6 is a shortened version of the ACQ that assesses the adequacy of asthma control and change in asthma control which occurs spontaneously or as a result of treatment. ACQ assesses symptoms and rescue bronchodilator use.~Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses. | Baseline (Week 0), Week 24, Week 52 |
| Asthma Impairment and Risk Questionnaire (AIRQ) | The Asthma Impairment and Risk Questionnaire (AIRQ) is a PRO tool intended to identify participants 12 years and older whose health may be at risk because of uncontrolled asthma.~It has 10 questions that ask about respiratory symptoms, activity limitation, sleep, rescue medication use, social activities, exercise, difficulty controlling asthma, and exacerbations. All items have a yes/no response option and the tool is scored by summing the total number of 'yes' responses. This sum score is used to assess level of asthma control where: 0-1 is well controlled, 2-4 is not well controlled, and 5-10 is very poorly controlled. Thus, a higher score indicates worse control status. | Baseline (Week 0), Week 24, Week 52 |
| St. George's Respiratory Questionnaire (SGRQ) | The SGRQ is a 50-item PRO instrument developed to measure the health status of participants with airway obstruction diseases.~The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ yields a total score and 3 components scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. Likewise, the domain scores range from 0 to 100, with higher scores indicative of greater impairment. | Baseline (Week 0), Week 24, Week 52 |
| Change from baseline in ACQ-6 score | Change from baseline in ACQ-6 score will be assessed. | Baseline (Week 0), Week 24, Week 52 |
| Change from baseline in AIRQ score | Change from baseline in AIRQ score will be assessed. | Baseline (Week 0), Week 24, Week 52 |
| Change from baseline in SGRQ score | Change from baseline in SGRQ score will be assessed. | Baseline (Week 0), Week 24, Week 52 |
| Proportion of ACQ-6 responders | ACQ-6 responders are defined as participants who achieve >=1 clinically important difference (MCID). | Baseline (Week 0), Week 24, Week 52 |
| Proportion of AIRQ responders | AIRQ responders is defined as participants who achieve ≥1 minimum clinically important difference (MCID). | Baseline (Week 0), Week 24, Week 52 |
| Proportion of SGRQ responders | SGRQ responders is defined as participants who achieve ≥1 minimum clinically important difference (MCID). | Baseline (Week 0), Week 24, Week 52 |
| Proportion of participants who require any systemic corticosteroid (SCS) use | Proportion of participants who require any SCS use in the 12-month periods before (baseline period) and after initiation of tezepelumab (up to study Week 52 -study period) will be assessed. | Baseline period up to study Week 52 |
| Cumulative annualized SCS dose | Cumulative annualized SCS dose in the 12-month periods before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed. | Baseline period up to study Week 52 |
| Proportion of participants who require longer-term (>30 consecutive days) SCS use | Proportion of participants who require longer-term (>30 consecutive days) SCS use in the 12-month periods before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed. | Baseline period up to study Week 52 |
| Number and type of asthma-related healthcare resource utilization (HRU) | Number and type of asthma-related HRU in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed. | Baseline period up to study Week 52 |
| Duration of asthma-related hospitalizations | Duration of asthma-related hospitalization in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52-study period) will be assessed. | Baseline period up to study Week 52 |
| AAER for asthma exacerbations (subgroups of participants) | The AAER based on asthma exacerbations in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: Blood eosinophil count (BEC) ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Proportion of participants with asthma exacerbations (subgroups of participants) | The proportion of participants with asthma exacerbations in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Proportion of participants who completed the 52 -week study with any reduction in total number of asthma exacerbations (subgroups of participants) | The proportion of participants who completed the 52 -week study period following tezepelumab initiation with any reduction, at least 50% reduction, and 100% reduction in total number of asthma exacerbations will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Week 0 to Week 52 |
| Cumulative asthma exacerbation days (subgroups of participants) | The cumulative asthma exacerbation days over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Rate of asthma exacerbations associated with hospitalizations (subgroups of participants) | The rate of asthma exacerbations associated with hospitalization over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Rate of asthma exacerbations associated with emergency department urgent care (ED/UC) visits (subgroups of participants) | The rate of asthma exacerbations associated with ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Rate of asthma exacerbations associated with hospitalizations or ED/UC visits over (subgroups of participants) | The rate of asthma exacerbations associated with hospitalizations or ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Number and type of asthma-related HRU (subgroups of participants) | Number and type of asthma related HRU in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Duration of asthma-related hospitalizations (subgroups of participants) | Duration of asthma-related hospitalization in the 12- month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
|
Inhaled corticosteroids (ICS), Post-Authorization, Baseline Blood eosinophil count (BEC), long-acting- β2 Agonist (LABA), Real-world participant population
|
Lung Diseases, Obstructive, Lung Diseases, Respiratory Hypersensitivity, Hypersensitivity, Immediate, Hypersensitivity, Immune System Diseases, Asthma, Bronchial Diseases, Respiratory Tract Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tezepelumab<br>Participants will be receiving 210 mg of tezepelumab every 4 weeks (Q4W) from Week 0 until Week 48. | Drug: Tezepelumab<br>* Participants will be receiving subcutaneous injection of tezepelumab.<br>* Other names: AMG 157 or MEDI9929;|
|
Effectiveness and Safety Study of Tezepelumab in Adults & Adolescent Participants With Severe Asthma in the United States
Study Overview
=================
Brief Summary
-----------------
To asses effectiveness and safety of tezepelumab in adult and adolescent participants with severe asthma including several under-studied populations in the United States.
Detailed Description
-----------------
This is a multicenter, single-arm, open-label, Post-authorization, Phase 4 study to assess the effectiveness of tezepelumab in the United States (US) among a real-world population of adults and adolescent participants with asthma requiring medium-dose to high-dose inhaled corticosteroids (ICS), with additional controller(s) for at least 12 months with documented history of at least 2 asthma exacerbations during the year prior to enrolment. The total duration of the study for each participant will be approximately 56 weeks. Approximately 400 participants will be enrolled. Participants will receive tezepelumab via subcutaneous injection at the study site, over a 48-week treatment period. The study also includes a post-dosing follow-up period from Weeks 48 to 52.
Official Title
-----------------
A Multicenter, Single-arm, Open-label, Post-Authorization, Phase 4 Effectiveness and Safety Study of Tezepelumab in Adult and Adolescent Participants With Severe Asthma Including Several Under-Studied Populations in the United States (PASSAGE)
Conditions
-----------------
Asthma
Intervention / Treatment
-----------------
* Drug: Tezepelumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female participant must be 12 years of age or older, at the time of signing the informed consent form or assent. Documented physician-diagnosed asthma for at least 12 months prior to enrollment and confirmed by the Investigator not to be due to alternative diagnoses. Documented treatment with medium- to high dose ICS as per Global Initiative for Asthma (GINA) guidelines (GINA 2021) for at least 12 months prior to enrollment. Use of additional asthma maintenance controller medication(s) in addition to ICS for at least 12 months prior to enrollment. The additional maintenance controller medication may be contained in a combination product (eg, ICS/ long-acting β-agonist (LABA)). Documented history of at least 2 asthma exacerbations during the 12 months prior to enrollment. Physician decision that participant is eligible for treatment with tezepelumab according to the approved United States product insert (USPI). Currently receiving care from specialist physicians (eg, pulmonologists and/or allergists). Provision of signed and dated written informed consent form. Exclusion Criteria: Any contraindication to tezepelumab as per the US approved product label or in the opinion of the Investigator. Comorbid diagnosis of severe or very severe chronic obstructive pulmonary disease (COPD) per GOLD guidelines (GOLD 2021). Use of biologics that are approved for the treatment of asthma within 4 months or 5 half- lives (whichever is longer) prior to enrollment. Participation in an interventional clinical trial for asthma within 12 months prior to enrollment. Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.
Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 130 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tezepelumab<br>Participants will be receiving 210 mg of tezepelumab every 4 weeks (Q4W) from Week 0 until Week 48. | Drug: Tezepelumab<br>* Participants will be receiving subcutaneous injection of tezepelumab.<br>* Other names: AMG 157 or MEDI9929;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized asthma exacerbation rate (AAER) | Asthma exacerbation will be defined by worsening of asthma symptoms that leads to temporary bolus/burst of systemic corticosteroids for at least 3 consecutive days, or an emergency department (ED) or urgent care visit due to asthma that required systemic corticosteroid (SCS), and/or inpatient hospitalization (≥24 hours) due to asthma. The AAER is based on exacerbations reported by the investigator over 52 weeks. The exacerbation rate will be compared between the 12 month period before (baseline period) and the 12 month period after initiation of tezepelumab (up to study Week 52 - study period). | Baseline period up to study Week 52 |
| Proportion of participants with asthma exacerbations | The proportion of participants with asthma exacerbations in the 12 month periods before (baseline period) and after initiation of tezepelumab (study period) (up to study Week 52 - study period) will be assessed. | Baseline period up to study Week 52 |
| Proportion of participants who completed the 52 -week study period with any reduction in total number of asthma exacerbations | The proportion of participants who completed the 52 -week study period following tezepelumab initiation with any reduction, at least 50% reduction, and 100% reduction in total number of asthma exacerbations will be assessed. | Baseline period up to study Week 52 |
| Cumulative asthma exacerbation days | The cumulative asthma exacerbation days over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first asthma exacerbation | The time to first exacerbation after initiation of tezepelumab will be assessed. | Week 0 to Week 52 |
| Rate of asthma exacerbations associated with hospitalizations | The rate of asthma exacerbations associated with hospitalization over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 |
| Rate of asthma exacerbations associated with emergency department /urgent care (ED/UC) visits | The rate of asthma exacerbations associated with ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 |
| Rate of asthma exacerbations associated with hospitalizations or ED/UC visits over | The rate of asthma exacerbations associated with hospitalizations or ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 |
| Proportion of participants with asthma exacerbations associated with hospitalizations or ED/UC visits | The proportion of participants with asthma exacerbations associated with hospitalizations or ED/UC visits in in the 12-month periods before (baseline period) and after initiation of tezepelumab (study period) (up to study Week 52) will be assessed. | Baseline period up to study Week 52 |
| Cumulative asthma exacerbation days associated with hospitalizations or ED/UC visits | The cumulative asthma exacerbation days associated with hospitalizations or ED/UC over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed. | Baseline period up to study Week 52 |
| Pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) | Lung function (FEV1) will be measured pre-bronchodilator (pre-BD) by spirometry test. | Baseline (Week 0), Week 24, Week 52 |
| Change from baseline in pre-bronchodilator FEV1 | Change from baseline in pre-bronchodilator FEV1 will be assessed as lung function parameters after initiation of tezepelumab. | Baseline (Week 0), Week 24, Week 52 |
| Proportion of pre-BD FEV1 responders | Proportion of pre-BD FEV1 responders is defined as participants who achieve either at least 5% or 100 mL improvement from baseline. | Baseline (Week 0), Week 24, Week 52 |
| Asthma Control Questionnaire (ACQ-6) | The ACQ-6 is a shortened version of the ACQ that assesses the adequacy of asthma control and change in asthma control which occurs spontaneously or as a result of treatment. ACQ assesses symptoms and rescue bronchodilator use. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses. | Baseline (Week 0), Week 24, Week 52 |
| Asthma Impairment and Risk Questionnaire (AIRQ) | The Asthma Impairment and Risk Questionnaire (AIRQ) is a PRO tool intended to identify participants 12 years and older whose health may be at risk because of uncontrolled asthma. It has 10 questions that ask about respiratory symptoms, activity limitation, sleep, rescue medication use, social activities, exercise, difficulty controlling asthma, and exacerbations. All items have a yes/no response option and the tool is scored by summing the total number of 'yes' responses. This sum score is used to assess level of asthma control where: 0-1 is well controlled, 2-4 is not well controlled, and 5-10 is very poorly controlled. Thus, a higher score indicates worse control status. | Baseline (Week 0), Week 24, Week 52 |
| St. George's Respiratory Questionnaire (SGRQ) | The SGRQ is a 50-item PRO instrument developed to measure the health status of participants with airway obstruction diseases. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ yields a total score and 3 components scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. This total score is expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. Likewise, the domain scores range from 0 to 100, with higher scores indicative of greater impairment. | Baseline (Week 0), Week 24, Week 52 |
| Change from baseline in ACQ-6 score | Change from baseline in ACQ-6 score will be assessed. | Baseline (Week 0), Week 24, Week 52 |
| Change from baseline in AIRQ score | Change from baseline in AIRQ score will be assessed. | Baseline (Week 0), Week 24, Week 52 |
| Change from baseline in SGRQ score | Change from baseline in SGRQ score will be assessed. | Baseline (Week 0), Week 24, Week 52 |
| Proportion of ACQ-6 responders | ACQ-6 responders are defined as participants who achieve >=1 clinically important difference (MCID). | Baseline (Week 0), Week 24, Week 52 |
| Proportion of AIRQ responders | AIRQ responders is defined as participants who achieve ≥1 minimum clinically important difference (MCID). | Baseline (Week 0), Week 24, Week 52 |
| Proportion of SGRQ responders | SGRQ responders is defined as participants who achieve ≥1 minimum clinically important difference (MCID). | Baseline (Week 0), Week 24, Week 52 |
| Proportion of participants who require any systemic corticosteroid (SCS) use | Proportion of participants who require any SCS use in the 12-month periods before (baseline period) and after initiation of tezepelumab (up to study Week 52 -study period) will be assessed. | Baseline period up to study Week 52 |
| Cumulative annualized SCS dose | Cumulative annualized SCS dose in the 12-month periods before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed. | Baseline period up to study Week 52 |
| Proportion of participants who require longer-term (>30 consecutive days) SCS use | Proportion of participants who require longer-term (>30 consecutive days) SCS use in the 12-month periods before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed. | Baseline period up to study Week 52 |
| Number and type of asthma-related healthcare resource utilization (HRU) | Number and type of asthma-related HRU in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed. | Baseline period up to study Week 52 |
| Duration of asthma-related hospitalizations | Duration of asthma-related hospitalization in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52-study period) will be assessed. | Baseline period up to study Week 52 |
| AAER for asthma exacerbations (subgroups of participants) | The AAER based on asthma exacerbations in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: Blood eosinophil count (BEC) ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Proportion of participants with asthma exacerbations (subgroups of participants) | The proportion of participants with asthma exacerbations in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Proportion of participants who completed the 52 -week study with any reduction in total number of asthma exacerbations (subgroups of participants) | The proportion of participants who completed the 52 -week study period following tezepelumab initiation with any reduction, at least 50% reduction, and 100% reduction in total number of asthma exacerbations will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Week 0 to Week 52 |
| Cumulative asthma exacerbation days (subgroups of participants) | The cumulative asthma exacerbation days over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Rate of asthma exacerbations associated with hospitalizations (subgroups of participants) | The rate of asthma exacerbations associated with hospitalization over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Rate of asthma exacerbations associated with emergency department urgent care (ED/UC) visits (subgroups of participants) | The rate of asthma exacerbations associated with ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Rate of asthma exacerbations associated with hospitalizations or ED/UC visits over (subgroups of participants) | The rate of asthma exacerbations associated with hospitalizations or ED/UC visits over 52 weeks before (baseline period) and after initiation of tezepelumab (study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Number and type of asthma-related HRU (subgroups of participants) | Number and type of asthma related HRU in the 12-month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
| Duration of asthma-related hospitalizations (subgroups of participants) | Duration of asthma-related hospitalization in the 12- month period before (baseline period) and after initiation of tezepelumab (up to study Week 52- study period) will be assessed in the following subgroups of participants: BEC ≥300 cells/microliter; BEC <300 cells/microliter; With a clinically-relevant allergy to a perennial aeroallergen; Without a clinically-relevant allergy to a perennial aeroallergen; Participants who identify as Black/African American; Adolescents (12-17 years); Comorbid diagnosis of mild to moderate COPD; Significant smoking history (≥10 pack-years of smoking). | Baseline period up to study Week 52 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inhaled corticosteroids (ICS), Post-Authorization, Baseline Blood eosinophil count (BEC), long-acting- β2 Agonist (LABA), Real-world participant population
|
NCT01798849
|
A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)
|
This study will evaluate safety, tolerability and effects on central diastolic blood pressure (cDBP) of MK-8892 given as single oral doses in healthy male participants (Panel A and B) and in male participants with mild-to-moderate hypertension (Panel C).
|
Up to three planned panels of either 8 healthy participants (Panels A and B) or 8 participants with mild to moderate hypertension (Panel C) will be enrolled. In Panels A and B, 8 participants will alternately receive single rising doses of MK-8892 or placebo. All doses will be administered in the fasted state, except Panel A, Period 5 in which a standard high-fat breakfast provided approximately 30 minutes prior to dosing.~Panel A will begin first. At least 3 days will elapse before participants in the alternate panel (Panel B) will receive the next higher dose. In Panel C, 8 mild to moderate hypertensive male participants will receive single rising doses of MK-8892 or placebo. Panel C may begin after the first 4 periods of Panels A and B have completed dosing. For all panels, there will be at least 7 days washout between treatment periods for any given participant. Participants may only be enrolled in one panel of the study. Subsequent doses in any panel will be administered only after careful evaluation of safety, tolerability, and pharmacodynamic effects of a given dose. All participants in periods of all panels (with exception of 2.0 mg fasted/fed periods) will be randomly assigned to either study drug or placebo, i.e a participant could be assigned to receive study drug in one period and placebo in another. As per the protocol allocation plan, the same participants will receive 2.0 mg MK-8892 in a fasted and fed state.The 2.0 mg MK-8892 fed/fasted data will be utilized for pharmacokinetic comparison and only the 2.0 mg MK-8892 fasted data will utilized for the analysis of the pharmacodynamics endpoints.~In addition, during any of the treatment periods if a participant demonstrates change in any one of the protocol-defined parameters lasting ≥1 hour, dose escalation in that participant will be halted and the participant may be withdrawn from the study or rechallenged at same dose or at a lower dose. Paricipants that meet criteria listed will be followed up until parameters no longer meet stopping rule criteria.
|
A Single Rising Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8892
|
Pulmonary Arterial Hypertension
|
* Drug: MK-8892
* Drug: Placebo for MK-8892
|
Inclusion Criteria:~Systolic blood pressure (SBP) > 110 and ≤ 140 mmHg for Panels A and B, SBP values of 140-175 mmHg and diastolic blood pressure (DBP) of 90-105 mmHg on at least three different occasions at the prestudy (screening) visit for Panel C. Participants being treated with medication for their hypertension may be included as long as they are titrated off of their medication~Body Mass Index (BMI) ≥ 18 kg/m^2 and ≤ 32 kg/m^2~Healthy (with the exception of hypertensive subjects in Panel C)~No clinically significant abnormality on electrocardiogram (ECG)~No history of clinically significant cardiac disease~No history of heart failure~Nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months~Exclusion Criteria:~Mentally or legally incapacitated~History of stroke, chronic seizures, or major neurological disorder~History of clinically significant endocrine, gastrointestinal, cardiovascular (except mild to moderate hypertension), hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases~Functional disability that can interfere with rising from a sitting position to the standing position~History of cancer (malignancy)~History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food~Positive for hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV)~Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks~Has participated in another investigational trial within 4 weeks~Unable to refrain from or anticipates the use of any medication during the study~Anticipates using medication for erectile dysfunction during the study~Uses or anticipates using organic nitrates during the study (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol)~Anticipates using cytochrome P450 inhibitors (e.g. ketoconazole) or inducers (e.g. rifampin) during the study~Consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages per day~Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, or other caffeinated beverages per day~Regular user (including recreational user) of illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year
|
18 Years
|
60 Years
|
Male
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants | An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event. | up to 7 weeks |
| Percentage of Participants Who Were Discontinued From the Study Due to an AE- Healthy Participants | An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event. | up to 7 weeks |
| Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP)- Healthy Participants | Central diastolic blood pressure measurements were obtained at predose and at 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease. | Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel) |
| Percentage of Participants Who Report 1 or More Adverse Events (AEs) - Hypertensive Participants | An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event. | up to 7 weeks |
| Percentage of Participants Who Were Discontinued From the Due to an AE - Hypertensive Participants | An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event. | up to 7 weeks |
| Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP) - Hypertensive Participants | Central diastolic blood pressure measurements were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease. | Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Healthy Participants | Peripheral diastolic blood pressure was measured using a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease. | Predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel) |
| Change in TWA0-24hrs for Heart Rate (HR) - Healthy Participants | Heart rate was measured predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose by a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease. | Predose (baseline) and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel) |
| Change in TWA0-24hr for Augmentation Index (AIx) - Healthy Participants | AIx was measured by applanation tonometry of the radial artery. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. | Predose (baseline) and 2, 4, 12, and 24 hours postdose (for each Dosing Period of Each Panel) |
| Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Hypertensive Participants | Peripheral blood pressure assessments were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose by using a validated automatic measuring device. Peripheral diastolic blood pressure was measured a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease. | Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel) |
| Change in TWA0-24hrs for Heart Rate (HR) - Hypertensive Participants | Heart rate was measured predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose by a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease. | Predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel) |
| TWA0-24hr for Augmentation Index (AIx) - Hypertensive Participants | AIx was measured by applanation tonometry of the radial artery. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease. | Predose to 24 hours Postdose (for each Dosing Period of Each Panel) |
| Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Healthy Participants | Blood samples taken at Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr. | Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose |
| Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Healthy Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892 - Healthy Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Maximum Concentration (Cmax) of MK-8892 - Healthy Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Time to Cmax (Tmax) of MK-8892 - Healthy Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Tmax. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Apparent Terminal Half-life (t1/2) of MK-8892 - Healthy Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose |
| Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892- Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Maximum Concentration (Cmax) of MK-8892- Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Time to Cmax (Tmax) of MK-8892- Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Tmax. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Apparent Terminal Half-life (t1/2) of MK-8892- Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of 2.0 mg MK-8892-Healthy Participants-Fasted/Fed | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose |
| Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Maximum Concentration (Cmax) of 2.0 mg MK-8892 - Healthy Participants- Fasted/Fed | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Apparent Terminal Half-life (t1/2) of 2.0 mg MK-8892 - Healthy Participants -Fasted/Fed | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2.A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
|
Pulmonary Arterial Hypertension, Hypertension, Pulmonary, Lung Diseases, Respiratory Tract Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A-Healthy<br>Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-8892 0.5 mg, 2.0 mg, 6.0 mg, 14 mg or 2.0 mg fed, and 2 participants received placebo. Dosing periods will alternate with Panel B. | Drug: MK-8892<br> <br> Drug: Placebo for MK-8892<br> <br> |
| Experimental: Panel B-Healthy<br>Within each of the 4 rising dose treatment periods, 6 participants received a single dose of MK-8892 1.0 mg, 4.0 mg, 9.0 mg or 12 mg, and 2 participants received placebo. Dosing periods will alternate with Panel A. | Drug: MK-8892<br> <br> Drug: Placebo for MK-8892<br> <br> |
| Experimental: Panel C-Mild/Moderate Hypertension<br>Within each of the 5 single dose treatment periods, 6 participants with mild to moderate hypertension received a single dose of MK-8892 0.5 mg, 1.0 mg, 2.0 mg or 6.0 mg, and 2 participants received placebo. Dosages will be determined by the results of Panels A and B. | Drug: MK-8892<br> <br> Drug: Placebo for MK-8892<br> <br> |
|
A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)
Study Overview
=================
Brief Summary
-----------------
This study will evaluate safety, tolerability and effects on central diastolic blood pressure (cDBP) of MK-8892 given as single oral doses in healthy male participants (Panel A and B) and in male participants with mild-to-moderate hypertension (Panel C).
Detailed Description
-----------------
Up to three planned panels of either 8 healthy participants (Panels A and B) or 8 participants with mild to moderate hypertension (Panel C) will be enrolled. In Panels A and B, 8 participants will alternately receive single rising doses of MK-8892 or placebo. All doses will be administered in the fasted state, except Panel A, Period 5 in which a standard high-fat breakfast provided approximately 30 minutes prior to dosing. Panel A will begin first. At least 3 days will elapse before participants in the alternate panel (Panel B) will receive the next higher dose. In Panel C, 8 mild to moderate hypertensive male participants will receive single rising doses of MK-8892 or placebo. Panel C may begin after the first 4 periods of Panels A and B have completed dosing. For all panels, there will be at least 7 days washout between treatment periods for any given participant. Participants may only be enrolled in one panel of the study. Subsequent doses in any panel will be administered only after careful evaluation of safety, tolerability, and pharmacodynamic effects of a given dose. All participants in periods of all panels (with exception of 2.0 mg fasted/fed periods) will be randomly assigned to either study drug or placebo, i.e a participant could be assigned to receive study drug in one period and placebo in another. As per the protocol allocation plan, the same participants will receive 2.0 mg MK-8892 in a fasted and fed state.The 2.0 mg MK-8892 fed/fasted data will be utilized for pharmacokinetic comparison and only the 2.0 mg MK-8892 fasted data will utilized for the analysis of the pharmacodynamics endpoints. In addition, during any of the treatment periods if a participant demonstrates change in any one of the protocol-defined parameters lasting ≥1 hour, dose escalation in that participant will be halted and the participant may be withdrawn from the study or rechallenged at same dose or at a lower dose. Paricipants that meet criteria listed will be followed up until parameters no longer meet stopping rule criteria.
Official Title
-----------------
A Single Rising Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8892
Conditions
-----------------
Pulmonary Arterial Hypertension
Intervention / Treatment
-----------------
* Drug: MK-8892
* Drug: Placebo for MK-8892
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Systolic blood pressure (SBP) > 110 and ≤ 140 mmHg for Panels A and B, SBP values of 140-175 mmHg and diastolic blood pressure (DBP) of 90-105 mmHg on at least three different occasions at the prestudy (screening) visit for Panel C. Participants being treated with medication for their hypertension may be included as long as they are titrated off of their medication Body Mass Index (BMI) ≥ 18 kg/m^2 and ≤ 32 kg/m^2 Healthy (with the exception of hypertensive subjects in Panel C) No clinically significant abnormality on electrocardiogram (ECG) No history of clinically significant cardiac disease No history of heart failure Nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months Exclusion Criteria: Mentally or legally incapacitated History of stroke, chronic seizures, or major neurological disorder History of clinically significant endocrine, gastrointestinal, cardiovascular (except mild to moderate hypertension), hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases Functional disability that can interfere with rising from a sitting position to the standing position History of cancer (malignancy) History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food Positive for hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV) Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks Has participated in another investigational trial within 4 weeks Unable to refrain from or anticipates the use of any medication during the study Anticipates using medication for erectile dysfunction during the study Uses or anticipates using organic nitrates during the study (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol) Anticipates using cytochrome P450 inhibitors (e.g. ketoconazole) or inducers (e.g. rifampin) during the study Consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages per day Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, or other caffeinated beverages per day Regular user (including recreational user) of illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A-Healthy<br>Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-8892 0.5 mg, 2.0 mg, 6.0 mg, 14 mg or 2.0 mg fed, and 2 participants received placebo. Dosing periods will alternate with Panel B. | Drug: MK-8892<br> <br> Drug: Placebo for MK-8892<br> <br> |
| Experimental: Panel B-Healthy<br>Within each of the 4 rising dose treatment periods, 6 participants received a single dose of MK-8892 1.0 mg, 4.0 mg, 9.0 mg or 12 mg, and 2 participants received placebo. Dosing periods will alternate with Panel A. | Drug: MK-8892<br> <br> Drug: Placebo for MK-8892<br> <br> |
| Experimental: Panel C-Mild/Moderate Hypertension<br>Within each of the 5 single dose treatment periods, 6 participants with mild to moderate hypertension received a single dose of MK-8892 0.5 mg, 1.0 mg, 2.0 mg or 6.0 mg, and 2 participants received placebo. Dosages will be determined by the results of Panels A and B. | Drug: MK-8892<br> <br> Drug: Placebo for MK-8892<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants | An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event. | up to 7 weeks |
| Percentage of Participants Who Were Discontinued From the Study Due to an AE- Healthy Participants | An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event. | up to 7 weeks |
| Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP)- Healthy Participants | Central diastolic blood pressure measurements were obtained at predose and at 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease. | Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel) |
| Percentage of Participants Who Report 1 or More Adverse Events (AEs) - Hypertensive Participants | An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event. | up to 7 weeks |
| Percentage of Participants Who Were Discontinued From the Due to an AE - Hypertensive Participants | An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event. | up to 7 weeks |
| Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP) - Hypertensive Participants | Central diastolic blood pressure measurements were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease. | Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Healthy Participants | Peripheral diastolic blood pressure was measured using a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease. | Predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel) |
| Change in TWA0-24hrs for Heart Rate (HR) - Healthy Participants | Heart rate was measured predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose by a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease. | Predose (baseline) and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel) |
| Change in TWA0-24hr for Augmentation Index (AIx) - Healthy Participants | AIx was measured by applanation tonometry of the radial artery. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. | Predose (baseline) and 2, 4, 12, and 24 hours postdose (for each Dosing Period of Each Panel) |
| Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Hypertensive Participants | Peripheral blood pressure assessments were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose by using a validated automatic measuring device. Peripheral diastolic blood pressure was measured a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease. | Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel) |
| Change in TWA0-24hrs for Heart Rate (HR) - Hypertensive Participants | Heart rate was measured predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose by a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease. | Predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel) |
| TWA0-24hr for Augmentation Index (AIx) - Hypertensive Participants | AIx was measured by applanation tonometry of the radial artery. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease. | Predose to 24 hours Postdose (for each Dosing Period of Each Panel) |
| Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Healthy Participants | Blood samples taken at Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr. | Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose |
| Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Healthy Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892 - Healthy Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Maximum Concentration (Cmax) of MK-8892 - Healthy Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Time to Cmax (Tmax) of MK-8892 - Healthy Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Tmax. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Apparent Terminal Half-life (t1/2) of MK-8892 - Healthy Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose |
| Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892- Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Maximum Concentration (Cmax) of MK-8892- Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Time to Cmax (Tmax) of MK-8892- Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Tmax. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Apparent Terminal Half-life (t1/2) of MK-8892- Hypertensive Participants | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of 2.0 mg MK-8892-Healthy Participants-Fasted/Fed | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose |
| Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Maximum Concentration (Cmax) of 2.0 mg MK-8892 - Healthy Participants- Fasted/Fed | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
| Apparent Terminal Half-life (t1/2) of 2.0 mg MK-8892 - Healthy Participants -Fasted/Fed | Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2.A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal. | Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose |
|
|
NCT05605678
|
Hemophilia Non-Interventional Study Prior to SerpinPC Intervention (PRESent-5)
|
The primary objective of this study is to obtain prospective baseline documentation of annualized bleeding rates (ABRs) and treatment under standard-of-care (SOC) therapy among participants with hemophilia A or B. Participants in the study may be eligible to enroll in future planned interventional studies to be conducted by Sponsor.
|
A Global, Non-interventional Study to Prospectively Evaluate Bleeding Episodes and Treatment Use in Patients With Hemophilia
|
Hemophilia A, Hemophilia B
|
* Other: No Intervention
|
Inclusion Criteria:~Male participants greater than or equal to (>=) 12 and less than or equal to (<=) 65 years of age~Who are capable of providing written informed consent (adolescent assent and parental/guardian consent when appropriate) for participation after reading the information and consent form and having the opportunity to discuss the study with the Investigator or their designee~With historically documented severe HemA (defined as factor VIII [FVIII] less than (<) 0.01 International Units per milliliter (IU/mL) [<1 percent {%}]), with or without inhibitors, or moderately severe to severe HemB (defined as factor IX [FIX] <=0.02 IU/mL [<=2%]) without inhibitors. Participants must be currently included in a prophylactic treatment program or if undergoing an on-demand treatment regimen must have had >=6 documented acute bleeding episodes (spontaneous or traumatic) that required coagulation factor infusion during the 6 months before enrollment OR: Historically documented HemB (defined as FIX <=0.05 IU/mL [<=5%]) with inhibitors with a historical or ongoing high titer inhibitor [>=5 Bethesda Units/mL] based on medical records or laboratory reports) and an ABR of >=6 in the 6 months before enrollment~Who are able to use a diary to document bleeding events and associated treatment~Exclusion Criteria:~With known thrombophilia~With body weight greater than (>)150 kilogram (kg) or body mass index >40~With known current inadequate hematologic function (eg, platelet count <100,000 per microliter [/mcL] and/or hemoglobin level <10 grams per deciliter [g/dL], <100 g/L), hepatic function (that is, total bilirubin >1.5*upper limit of normal [ULN] [excluding Gilbert syndrome], aspartate transferase and/or alanine aminotransferase levels >3*ULN; clinical signs or known laboratory or radiographic evidence consistent with cirrhosis of the liver) or renal function (that is, serum creatinine >2*ULN; based on medical records or available laboratory reports)~With previous deep vein thrombosis and pulmonary embolism, myocardial infarction, or stroke~With history of intolerance to subcutaneous injections~With known current uncontrolled hypertension (systolic blood pressure >160 millimeter of mercury (mm Hg); diastolic blood pressure >100 mm Hg; based on medical records)~With active cancer or requires therapy for cancer, except for basal cell carcinoma~With concurrent participation in an interventional clinical trial~With current or planned use of emicizumab~With prior, ongoing, or planned treatment with gene therapy for hemophilia~With history of or other evidence of recent alcohol or drug abuse as determined by the Investigator or their designee (in the 12 months before enrollment)~With known Human Immunodeficiency Virus (HIV) infection with CD4 count (or T-cell count) of <200 cells/mcL within 24 weeks before enrollment~With current or planned treatment with anticoagulant or antiplatelet drugs~With any other significant conditions or comorbidities that, in the opinion of the Investigator or their designee, would make the participant unsuitable for enrollment
|
12 Years
|
65 Years
|
Male
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Bleeding Rate (ABR) for Treated Bleeds and All Bleeds | ABR for treated bleeds and all bleeds at the participant and bleed level (excluding bleeding episodes during surgery and/or procedures). | Minimum 12 weeks |
| Average Dose (IU/kg) of Associated Treatment Received for Bleeding Episodes per Hemophilia Product per Time Period and per Bleeding Episode | | Minimum 12 weeks |
|
Hemophilia, Prospective
|
Hemophilia A, Hemophilia B, Blood Coagulation Disorders, Inherited, Blood Coagulation Disorders, Hematologic Diseases, Coagulation Protein Disorders, Hemorrhagic Disorders, Genetic Diseases, Inborn, Genetic Diseases, X-Linked
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| All Eligible Participants<br>All Participants diagnosed with severe HemA with or without inhibitors, moderately severe to severe HemB, or HemB with inhibitors will be enrolled and continue to receive their usual hemophilia treatment regimen under SOC therapy. Bleeding episodes and treatment data will be collected during the prospective follow up period in a diary. No intervention will be administered as part of this study. | Other: No Intervention<br>* This is a non-interventional study.<br>|
|
Hemophilia Non-Interventional Study Prior to SerpinPC Intervention (PRESent-5)
Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to obtain prospective baseline documentation of annualized bleeding rates (ABRs) and treatment under standard-of-care (SOC) therapy among participants with hemophilia A or B. Participants in the study may be eligible to enroll in future planned interventional studies to be conducted by Sponsor.
Official Title
-----------------
A Global, Non-interventional Study to Prospectively Evaluate Bleeding Episodes and Treatment Use in Patients With Hemophilia
Conditions
-----------------
Hemophilia A, Hemophilia B
Intervention / Treatment
-----------------
* Other: No Intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male participants greater than or equal to (>=) 12 and less than or equal to (<=) 65 years of age Who are capable of providing written informed consent (adolescent assent and parental/guardian consent when appropriate) for participation after reading the information and consent form and having the opportunity to discuss the study with the Investigator or their designee With historically documented severe HemA (defined as factor VIII [FVIII] less than (<) 0.01 International Units per milliliter (IU/mL) [<1 percent {%}]), with or without inhibitors, or moderately severe to severe HemB (defined as factor IX [FIX] <=0.02 IU/mL [<=2%]) without inhibitors. Participants must be currently included in a prophylactic treatment program or if undergoing an on-demand treatment regimen must have had >=6 documented acute bleeding episodes (spontaneous or traumatic) that required coagulation factor infusion during the 6 months before enrollment OR: Historically documented HemB (defined as FIX <=0.05 IU/mL [<=5%]) with inhibitors with a historical or ongoing high titer inhibitor [>=5 Bethesda Units/mL] based on medical records or laboratory reports) and an ABR of >=6 in the 6 months before enrollment Who are able to use a diary to document bleeding events and associated treatment Exclusion Criteria: With known thrombophilia With body weight greater than (>)150 kilogram (kg) or body mass index >40 With known current inadequate hematologic function (eg, platelet count <100,000 per microliter [/mcL] and/or hemoglobin level <10 grams per deciliter [g/dL], <100 g/L), hepatic function (that is, total bilirubin >1.5*upper limit of normal [ULN] [excluding Gilbert syndrome], aspartate transferase and/or alanine aminotransferase levels >3*ULN; clinical signs or known laboratory or radiographic evidence consistent with cirrhosis of the liver) or renal function (that is, serum creatinine >2*ULN; based on medical records or available laboratory reports) With previous deep vein thrombosis and pulmonary embolism, myocardial infarction, or stroke With history of intolerance to subcutaneous injections With known current uncontrolled hypertension (systolic blood pressure >160 millimeter of mercury (mm Hg); diastolic blood pressure >100 mm Hg; based on medical records) With active cancer or requires therapy for cancer, except for basal cell carcinoma With concurrent participation in an interventional clinical trial With current or planned use of emicizumab With prior, ongoing, or planned treatment with gene therapy for hemophilia With history of or other evidence of recent alcohol or drug abuse as determined by the Investigator or their designee (in the 12 months before enrollment) With known Human Immunodeficiency Virus (HIV) infection with CD4 count (or T-cell count) of <200 cells/mcL within 24 weeks before enrollment With current or planned treatment with anticoagulant or antiplatelet drugs With any other significant conditions or comorbidities that, in the opinion of the Investigator or their designee, would make the participant unsuitable for enrollment
Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| All Eligible Participants<br>All Participants diagnosed with severe HemA with or without inhibitors, moderately severe to severe HemB, or HemB with inhibitors will be enrolled and continue to receive their usual hemophilia treatment regimen under SOC therapy. Bleeding episodes and treatment data will be collected during the prospective follow up period in a diary. No intervention will be administered as part of this study. | Other: No Intervention<br>* This is a non-interventional study.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Bleeding Rate (ABR) for Treated Bleeds and All Bleeds | ABR for treated bleeds and all bleeds at the participant and bleed level (excluding bleeding episodes during surgery and/or procedures). | Minimum 12 weeks |
| Average Dose (IU/kg) of Associated Treatment Received for Bleeding Episodes per Hemophilia Product per Time Period and per Bleeding Episode | | Minimum 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hemophilia, Prospective
|
|||
NCT01229891
|
Comparison of Efficacy of Vitamin D and Vitamin D-calcium Fortified Yogurt Drink in Diabetic Patients
|
The aim of this study is to evaluate the possible effects of daily intake of yogurt drink fortified with vitamin D alone or with vitamin D + calcium on some selected glycemic, metabolic, inflammatory and oxidative stress markers in patients with type 2 diabetes (T2DM).
|
ninety diabetic patients will be selected. Patients who are receiving vitamin D, calcium or omega-3 supplements within the last three months will be excluded. Patients will be assigned randomly to one of the three intervention groups. 1. Plain yogurt drink 2. Vitamin D-fortified yogurt drink 3. Vitamin D-calcium fortified yogurt drink. Each patient will consume 2 servings of yogurt drink every day for 3 months with lunch and dinner. At the first and last visits, dietary and laboratory assessments will be performed for all patients. Primary outcomes are improvement in glycemic, inflammatory and immunity markers and secondary outcome is prevention of long-term diabetic complications.
|
Comparison of Efficacy of Vitamin D and Vitamin D-calcium Fortified Yogurt Drink on Glycemic, Metabolic, Inflammatory, Immunity and Oxidative Stress Markers in Type 2 Diabetes
|
Type 2 Diabetes
|
* Dietary Supplement: plain yogurt drink
* Dietary Supplement: vitamin D fortified yogurt drink
* Dietary Supplement: vitamin D-calcium yogurt drink
|
Inclusion Criteria:Age:~30 to 50 years,~Fasting blood glucose ≥ 126 mg/dl~Exclusion Criteria:~Receiving vitamin D or calcium or omega-3 supplements within the last three months,~On any medication which could potentially influence vitamin D metabolism (notably estrogens, and calcitonin) within the last three months,~Any other concomitant disease such as renal, hepatic, and other endocrinological disorders, and malignancies, which could influence vitamin D metabolism.~Receiving insulin or any change in the type and/or dose of the current hypoglycemic medications
|
30 Years
|
60 Years
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum 25-hydroxyvitamin D | | 12-week |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Serum Glucose (FSG) | | 12-week |
| Insulin | fasting serum insulin concentration | 12-week |
| Hemoglobin A1c (HbA1c) | | 12-week |
| Serum Triglyceride (TG) | | 12-week |
| Serum Total Cholesterol (Tchol) | | 12-week |
| Serum Low Density Lipoprotein (LDL) | | 12-week |
| Serum High Density Lipoprotein (HDL) | | 12-week |
|
vitamin D fortification, yogurt drink, type 2 diabetes, efficacy
|
Vitamin D, Ergocalciferols, Cholecalciferol, Vitamins, Micronutrients, Physiological Effects of Drugs, Calcium-Regulating Hormones and Agents, Bone Density Conservation Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Plain yogurt drink<br>daily intake of two bottle (250 mL) plain yogurt drink | Dietary Supplement: plain yogurt drink<br>* daily intake of two bottle of plain yogurt drink<br>* Other names: PY;|
| Experimental: vitamin D-fortified yogurt drink<br>daily intake of two bottle yogurt drink fortified with 500 IU vitamin D/250 mL | Dietary Supplement: vitamin D fortified yogurt drink<br>* daily intake of two bottle of yogurt drink fortified with 500 IU vitamin D/250 mL<br>* Other names: DY;|
| Experimental: vitamin D-calcium yogurt drink<br>daily intake of two bottle of yogurt drink fortified with 500 IU vitamin D and 250 mg calcium/250 mL | Dietary Supplement: vitamin D-calcium yogurt drink<br>* daily intake of two bottle of yogurt drink fortified with 500 IU vitamin D and 250 mg calcium/250 ml package<br>* Other names: DCY;|
|
Comparison of Efficacy of Vitamin D and Vitamin D-calcium Fortified Yogurt Drink in Diabetic Patients
Study Overview
=================
Brief Summary
-----------------
The aim of this study is to evaluate the possible effects of daily intake of yogurt drink fortified with vitamin D alone or with vitamin D + calcium on some selected glycemic, metabolic, inflammatory and oxidative stress markers in patients with type 2 diabetes (T2DM).
Detailed Description
-----------------
ninety diabetic patients will be selected. Patients who are receiving vitamin D, calcium or omega-3 supplements within the last three months will be excluded. Patients will be assigned randomly to one of the three intervention groups. 1. Plain yogurt drink 2. Vitamin D-fortified yogurt drink 3. Vitamin D-calcium fortified yogurt drink. Each patient will consume 2 servings of yogurt drink every day for 3 months with lunch and dinner. At the first and last visits, dietary and laboratory assessments will be performed for all patients. Primary outcomes are improvement in glycemic, inflammatory and immunity markers and secondary outcome is prevention of long-term diabetic complications.
Official Title
-----------------
Comparison of Efficacy of Vitamin D and Vitamin D-calcium Fortified Yogurt Drink on Glycemic, Metabolic, Inflammatory, Immunity and Oxidative Stress Markers in Type 2 Diabetes
Conditions
-----------------
Type 2 Diabetes
Intervention / Treatment
-----------------
* Dietary Supplement: plain yogurt drink
* Dietary Supplement: vitamin D fortified yogurt drink
* Dietary Supplement: vitamin D-calcium yogurt drink
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria:Age: 30 to 50 years, Fasting blood glucose ≥ 126 mg/dl Exclusion Criteria: Receiving vitamin D or calcium or omega-3 supplements within the last three months, On any medication which could potentially influence vitamin D metabolism (notably estrogens, and calcitonin) within the last three months, Any other concomitant disease such as renal, hepatic, and other endocrinological disorders, and malignancies, which could influence vitamin D metabolism. Receiving insulin or any change in the type and/or dose of the current hypoglycemic medications
Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 60 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Plain yogurt drink<br>daily intake of two bottle (250 mL) plain yogurt drink | Dietary Supplement: plain yogurt drink<br>* daily intake of two bottle of plain yogurt drink<br>* Other names: PY;|
| Experimental: vitamin D-fortified yogurt drink<br>daily intake of two bottle yogurt drink fortified with 500 IU vitamin D/250 mL | Dietary Supplement: vitamin D fortified yogurt drink<br>* daily intake of two bottle of yogurt drink fortified with 500 IU vitamin D/250 mL<br>* Other names: DY;|
| Experimental: vitamin D-calcium yogurt drink<br>daily intake of two bottle of yogurt drink fortified with 500 IU vitamin D and 250 mg calcium/250 mL | Dietary Supplement: vitamin D-calcium yogurt drink<br>* daily intake of two bottle of yogurt drink fortified with 500 IU vitamin D and 250 mg calcium/250 ml package<br>* Other names: DCY;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum 25-hydroxyvitamin D | | 12-week |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Serum Glucose (FSG) | | 12-week |
| Insulin | fasting serum insulin concentration | 12-week |
| Hemoglobin A1c (HbA1c) | | 12-week |
| Serum Triglyceride (TG) | | 12-week |
| Serum Total Cholesterol (Tchol) | | 12-week |
| Serum Low Density Lipoprotein (LDL) | | 12-week |
| Serum High Density Lipoprotein (HDL) | | 12-week |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vitamin D fortification, yogurt drink, type 2 diabetes, efficacy
|
NCT01754428
|
Surveillance Study of Respiratory Syncytial Virus Infection (RSV) in Subjects < 24 Months of Age
|
The purpose of this study is to collect clinical outcome and nasal viral load information.
|
There is no vaccine available to prevent Respiratory Syncytial Virus disease; however, a humanized monoclonal antibody is approved for the prevention of Respiratory Syncytial Virus infection in pediatric patients at high risk of disease (eg, pre-term infants, congenital heart disease, and chronic lung disease). Beyond this high-risk group, infection is common in otherwise healthy infants and can be severe, leading to hospitalization and while uncommon, death. Each year in the United States, approximately 100,000 Respiratory Syncytial Virus-related hospitalizations occur in low risk infants. Currently, treatment of infants suffering from Respiratory Syncytial Virus disease is limited to supportive care with the goal of maintaining adequate oxygenation and nutrition.~The availability of a novel anti-Respiratory Syncytial Virus therapeutic that reduces the number of hospitalizations related to Respiratory Syncytial Virus infection would fulfill an unmet medical need in the pediatric population. For maximum effect, such a treatment should be administered as early as possible in the course of infection. Accordingly, the opportunities for early intervention with an anti-Respiratory Syncytial Virus therapeutic are in the outpatient setting, prior to hospitalization. However, the incidence of Respiratory Syncytial Virus-related hospitalization, as well as the natural history and viral dynamics of Respiratory Syncytial Virus infection, remain undefined in the outpatient setting. A better understanding of the prevalence of Respiratory Syncytial Virus infection and subsequent hospitalization rates among symptomatic infants as well as the early disease course of Respiratory Syncytial Virus infection will help in the design of clinical trials needed to assess the efficacy of an anti-Respiratory Syncytial Virus therapeutic developed by Gilead Sciences.
|
A Multi-Center, Outpatient, Surveillance Study of Respiratory Syncytial Virus (RSV) Infection and Respiratory Syncytial Virus-related Hospitalizations Among Subjects < 24 Months of Age With a Medically Attended Respiratory Tract Infection
|
Respiratory Syncytial Virus Infections
|
Inclusion Criteria:~< 24 months of age~≥ 35 weeks gestational age at birth~Signs of acute Respiratory Tract Infection < 5 days~Ability to contact parent or legal guardian for follow up~Exclusion Criteria:~Ongoing Respiratory Tract Infection~Lung disease~Heart disease~Respiratory Syncytial Virus medication in the last 6 months~Participation in a study with investigational medicinal product in the last 28 days
| null |
24 Months
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the percentage of medically attended Respiratory Syncytial Virus- positive subjects hospitalized for Respiratory Syncytial Virus related symptoms | | Up to seven months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Respiratory Syncytial Virus-positive subjects who sought medical attention, as a result of the Respiratory Tract Infection, after Visit 1 | | Up to seven months |
|
Respiratory, Syncytial, Virus, RSV
|
Infections, Communicable Diseases, Virus Diseases, Respiratory Syncytial Virus Infections, Disease Attributes, Pathologic Processes, Pneumovirus Infections, Paramyxoviridae Infections, Mononegavirales Infections, RNA Virus Infections
|
Surveillance Study of Respiratory Syncytial Virus Infection (RSV) in Subjects < 24 Months of Age
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to collect clinical outcome and nasal viral load information.
Detailed Description
-----------------
There is no vaccine available to prevent Respiratory Syncytial Virus disease; however, a humanized monoclonal antibody is approved for the prevention of Respiratory Syncytial Virus infection in pediatric patients at high risk of disease (eg, pre-term infants, congenital heart disease, and chronic lung disease). Beyond this high-risk group, infection is common in otherwise healthy infants and can be severe, leading to hospitalization and while uncommon, death. Each year in the United States, approximately 100,000 Respiratory Syncytial Virus-related hospitalizations occur in low risk infants. Currently, treatment of infants suffering from Respiratory Syncytial Virus disease is limited to supportive care with the goal of maintaining adequate oxygenation and nutrition. The availability of a novel anti-Respiratory Syncytial Virus therapeutic that reduces the number of hospitalizations related to Respiratory Syncytial Virus infection would fulfill an unmet medical need in the pediatric population. For maximum effect, such a treatment should be administered as early as possible in the course of infection. Accordingly, the opportunities for early intervention with an anti-Respiratory Syncytial Virus therapeutic are in the outpatient setting, prior to hospitalization. However, the incidence of Respiratory Syncytial Virus-related hospitalization, as well as the natural history and viral dynamics of Respiratory Syncytial Virus infection, remain undefined in the outpatient setting. A better understanding of the prevalence of Respiratory Syncytial Virus infection and subsequent hospitalization rates among symptomatic infants as well as the early disease course of Respiratory Syncytial Virus infection will help in the design of clinical trials needed to assess the efficacy of an anti-Respiratory Syncytial Virus therapeutic developed by Gilead Sciences.
Official Title
-----------------
A Multi-Center, Outpatient, Surveillance Study of Respiratory Syncytial Virus (RSV) Infection and Respiratory Syncytial Virus-related Hospitalizations Among Subjects < 24 Months of Age With a Medically Attended Respiratory Tract Infection
Conditions
-----------------
Respiratory Syncytial Virus Infections
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: < 24 months of age ≥ 35 weeks gestational age at birth Signs of acute Respiratory Tract Infection < 5 days Ability to contact parent or legal guardian for follow up Exclusion Criteria: Ongoing Respiratory Tract Infection Lung disease Heart disease Respiratory Syncytial Virus medication in the last 6 months Participation in a study with investigational medicinal product in the last 28 days
Ages Eligible for Study
-----------------
Maximum Age: 24 Months
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the percentage of medically attended Respiratory Syncytial Virus- positive subjects hospitalized for Respiratory Syncytial Virus related symptoms | | Up to seven months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Respiratory Syncytial Virus-positive subjects who sought medical attention, as a result of the Respiratory Tract Infection, after Visit 1 | | Up to seven months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Respiratory, Syncytial, Virus, RSV
|
|||
NCT02561949
|
Adapting Mental Health Interventions for War-Affected Youth Through Employment Programs
|
The research will first examine data obtained from YRI participants to investigate effects of the group sessions on psychosocial functioning outcomes in youth aged 15 - 24. The research also intends to examine whether youth participating in YRI and complementary income generating activities will fare better than an employment only control group. Finally, the research intends to examine whether utilizing lay health workers are a is cost-effective and scalable method for addressing mental health concerns.~The research will investigate the following hypotheses:~Participants who are exposed to YRI will demonstrate greater reduction in mental health and behavioral problems than participants who are waitlisted for YRI over the same period; emotion regulation will operate as a major mechanism of YRI improvements; high comorbidity will be a treatment modifier;~Improvements in mental health and functioning due to YRI will lead to (mediate) greater employment outcomes and superior economic self-sufficiency over time; and~Homelessness, orphanhood, young parenthood, and high problems in emotion regulation co-morbid with other mental health conditions will be major moderators lessening the effectiveness of YRI.~Lay and trained practitioners at agencies participating in the combined mental health-employment program will demonstrate high fidelity to evidence-based treatment components and that good satisfaction, social support, and professional exchange of evidence-based practices will emerge.
|
In Sierra Leone, a dangerous gap remains between long-term psychosocial needs and adequate services. As youth affected by the war begin to enter adulthood, they face new challenges including unemployment, interrupted education, the need to support families, marginalization and stigma, as well as the remaining psychological effects of exposure to war. Healthy social integration is critical to the long-term wellbeing of this generation, but the evidence base on effective interventions to improve skills and self-efficacy is severely limited. Despite the high burden of mental health problems among war-affected youth in Sub-Saharan Africa, few empirically-supported behavioral treatments (ESBTs) or evidence-based interventions have been implemented in this region. This study stands to make an important contribution to knowledge on effective and culturally-sensitive mental health services that can be implemented in settings fraught by multiple hardships, including war, poverty, low educational attainment, and other hardships.~This exploratory randomized control study of youth aged 15-24 comparing outcomes among youth participating in YRI proceeding enrollment in an income generating activity program (YRI + EP) to a control group that participates only in income generating activity programs (EP). This study is not fully powered to detect differences between groups and is instead a test of the intervention feasibility and acceptability, with quantitative participant assessments occurring at baseline, 3-months, 6-months, and 12-months with respect to employment related measures, and participant and interventionists interviews to elucidate mechanisms by which the intervention was more or less successful.~The YRI is an evidence-based group intervention developed in 2010 to address key emotional, behavioral, and functioning difficulties identified by the PI's prior longitudinal study of war-affected youth. The YRI has three overarching goals: (1) To improve interpersonal and community relationships through work with youth and community members; (2) To help vulnerable youth develop skills in emotional regulation, problem-solving, and interpersonal interactions necessary to be successful members of their communities; (3) To promote the healthy integration of difficult memories for youth who experience difficulties due to traumatic exposure. Primary mental health outcomes include decreased anxiety, hostility, and depression, and increased pro-social attitudes, as measured by the Oxford Refugee Studies Psychosocial Adjustment Scale and the African Youth Psychosocial Assessment. During this study YRI will be delivered by trained counselors,~Income generating activity programming will be carried out by GOAL and their partner St. George's Foundation through use of their current grant funding. GOAL focuses on supporting people in need by providing healthcare resources, advocating and advancing child protection practices and policies, and administering livelihood programs to empower them improve their lives in a sustainable manner. The St. George's Foundation's addresses child welfare concerns by actively reaching out to homeless and orphaned children. Their already existing employment program is 4 months in length and consists of skills training, soft skills development (primarily in numeracy and literacy), and a cash transfer of $200. The employment intervention is carried out by social workers and counselors, who have been trained to support delivery of the intervention.
|
Adapting Mental Health Interventions for War-Affected Youth Through Employment Programs in Sierra Leone
|
Anxiety Disorder/Anxiety State, Depressive Disorder/Psychology, Social Problems/Psychology, Violence, Non-accidental
|
* Behavioral: YRI
* Other: Income generating activity program
|
Inclusion Criteria:~Participants must be between the ages 15-24 (UN definition of youth);~Participants must have an elevated score on internalizing (depression/anxiety) or externalizing (aggression/ hostility) on a measure validated for use in Sierra Leone;~Participants must report some impairment in daily functioning as a result of emotional or behavior problems based on a series of questions adapted from the WHODAS; and~Participants must neither be enrolled in school nor have gainful employment of 20 or more hours of work per week over the past four weeks.~Exclusion Criteria:~Participant fails to meet the age requirements;~Participant is either currently enrolled in school or has gainful employment of 20 hours or more of work per week over the past four weeks;~Participant is not in favor of joining an employment program;~Participants does not have an elevated score on internalizing (depression/anxiety) or externalizing (aggression/ hostility) on a measure validated for use in Sierra Leone;~Participant does not report some impairment in daily functioning as a result of emotional or behavior problems based on a series of questions adapted from the WHODAS;~Participant identified by clinical staff as: (a) experiencing suicidality, or (b) psychosis.~Participants at risk of harm to themselves or others, as well as those requiring treatment beyond the scope of YRI will be referred to local mental health or social work treatment facilitates as appropriate.
|
15 Years
|
24 Years
|
All
|
No
|
Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in % of youth with improved health outcomes | The percent of youth with improved mental health and daily functioning will be measured through a quantitative assessment battery including measurements from the Hopkins Symptoms Checklist, Oxford Measure of Psychosocial Adjustment, Ways of Coping Questionnaire, UCLA Traumatic Stress Disorder Reaction Index, World Health Organization Disability Adjustment Scale, Difficulties in Emotion Regulation Scale. | Baseline, 3 months, 6 months, and 12 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| YRI Fidelity Protocol | Feedback will be gained on the more or less successful programmatic mechanisms and the intervention quality and sustainability through semi-structured qualitative exit interviews with interventionists and youth. | 3 months |
| Change in knowledge, attitudes, and behaviors of youth around employment and access to employment services. | Supervisors will assess youth on attendance, workplace performance, economic self-sufficiency, financial consumption/expenditures, savings and employment-related behaviors (supervisors will be interviewed about each young person blind to their group assignment). | 6 months |
|
War, Depression/therapy, Developing Countries, Interpersonal Relations, Life Change Events, Psychotherapy, group, Resilience, Psychological, Sierra Leone, Survivors/psychology, Social Adjustment, Social Behavior
|
Depressive Disorder, Anxiety Disorders, Mood Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YRI + Employment Program<br>Immediately following enrollment participants will complete the YRI intervention, followed by an income generating activity program. | Behavioral: YRI<br>* Youth Readiness Intervention (YRI) is an innovative, evidence-based mental health intervention to address co-morbid difficulties with externalizing problems (anger/emotion dysregulation) and internalizing problems (hopelessness/anxiety) among violence-affected youth. YRI methodology draws on evidence-based treatment elements commonly used in both cognitive-behavioral intervention and group interpersonal therapy. YRI has cross-cutting efficacy across a range of mental health conditions common in violence-affected youth. YRI will be delivered in 12 sessions over the course of 3 months.<br>* Other names: Youth Readiness Intervention;Other: Income generating activity program<br>* Income generating activity programming will be carried out by GOAL in partnership with St. George's foundation through use of their current funding. GOAL focuses on supporting people in need by providing healthcare resources, advocating and advancing child protection practices and policies, and administering livelihood programs to empower them improve their lives in a sustainable manner. The St. George's Foundation's addresses child welfare concerns by actively reaching out to homeless and orphaned children. The program is 4 months in length and consists of skills training, soft skills development (primarily in numeracy and literacy), and a cash transfer of $200.<br>|
| Experimental: Employment Program<br>Immediately following enrollment participants will complete an income generating activity program. | Other: Income generating activity program<br>* Income generating activity programming will be carried out by GOAL in partnership with St. George's foundation through use of their current funding. GOAL focuses on supporting people in need by providing healthcare resources, advocating and advancing child protection practices and policies, and administering livelihood programs to empower them improve their lives in a sustainable manner. The St. George's Foundation's addresses child welfare concerns by actively reaching out to homeless and orphaned children. The program is 4 months in length and consists of skills training, soft skills development (primarily in numeracy and literacy), and a cash transfer of $200.<br>|
|
Adapting Mental Health Interventions for War-Affected Youth Through Employment Programs
Study Overview
=================
Brief Summary
-----------------
The research will first examine data obtained from YRI participants to investigate effects of the group sessions on psychosocial functioning outcomes in youth aged 15 - 24. The research also intends to examine whether youth participating in YRI and complementary income generating activities will fare better than an employment only control group. Finally, the research intends to examine whether utilizing lay health workers are a is cost-effective and scalable method for addressing mental health concerns. The research will investigate the following hypotheses: Participants who are exposed to YRI will demonstrate greater reduction in mental health and behavioral problems than participants who are waitlisted for YRI over the same period; emotion regulation will operate as a major mechanism of YRI improvements; high comorbidity will be a treatment modifier; Improvements in mental health and functioning due to YRI will lead to (mediate) greater employment outcomes and superior economic self-sufficiency over time; and Homelessness, orphanhood, young parenthood, and high problems in emotion regulation co-morbid with other mental health conditions will be major moderators lessening the effectiveness of YRI. Lay and trained practitioners at agencies participating in the combined mental health-employment program will demonstrate high fidelity to evidence-based treatment components and that good satisfaction, social support, and professional exchange of evidence-based practices will emerge.
Detailed Description
-----------------
In Sierra Leone, a dangerous gap remains between long-term psychosocial needs and adequate services. As youth affected by the war begin to enter adulthood, they face new challenges including unemployment, interrupted education, the need to support families, marginalization and stigma, as well as the remaining psychological effects of exposure to war. Healthy social integration is critical to the long-term wellbeing of this generation, but the evidence base on effective interventions to improve skills and self-efficacy is severely limited. Despite the high burden of mental health problems among war-affected youth in Sub-Saharan Africa, few empirically-supported behavioral treatments (ESBTs) or evidence-based interventions have been implemented in this region. This study stands to make an important contribution to knowledge on effective and culturally-sensitive mental health services that can be implemented in settings fraught by multiple hardships, including war, poverty, low educational attainment, and other hardships. This exploratory randomized control study of youth aged 15-24 comparing outcomes among youth participating in YRI proceeding enrollment in an income generating activity program (YRI + EP) to a control group that participates only in income generating activity programs (EP). This study is not fully powered to detect differences between groups and is instead a test of the intervention feasibility and acceptability, with quantitative participant assessments occurring at baseline, 3-months, 6-months, and 12-months with respect to employment related measures, and participant and interventionists interviews to elucidate mechanisms by which the intervention was more or less successful. The YRI is an evidence-based group intervention developed in 2010 to address key emotional, behavioral, and functioning difficulties identified by the PI's prior longitudinal study of war-affected youth. The YRI has three overarching goals: (1) To improve interpersonal and community relationships through work with youth and community members; (2) To help vulnerable youth develop skills in emotional regulation, problem-solving, and interpersonal interactions necessary to be successful members of their communities; (3) To promote the healthy integration of difficult memories for youth who experience difficulties due to traumatic exposure. Primary mental health outcomes include decreased anxiety, hostility, and depression, and increased pro-social attitudes, as measured by the Oxford Refugee Studies Psychosocial Adjustment Scale and the African Youth Psychosocial Assessment. During this study YRI will be delivered by trained counselors, Income generating activity programming will be carried out by GOAL and their partner St. George's Foundation through use of their current grant funding. GOAL focuses on supporting people in need by providing healthcare resources, advocating and advancing child protection practices and policies, and administering livelihood programs to empower them improve their lives in a sustainable manner. The St. George's Foundation's addresses child welfare concerns by actively reaching out to homeless and orphaned children. Their already existing employment program is 4 months in length and consists of skills training, soft skills development (primarily in numeracy and literacy), and a cash transfer of $200. The employment intervention is carried out by social workers and counselors, who have been trained to support delivery of the intervention.
Official Title
-----------------
Adapting Mental Health Interventions for War-Affected Youth Through Employment Programs in Sierra Leone
Conditions
-----------------
Anxiety Disorder/Anxiety State, Depressive Disorder/Psychology, Social Problems/Psychology, Violence, Non-accidental
Intervention / Treatment
-----------------
* Behavioral: YRI
* Other: Income generating activity program
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must be between the ages 15-24 (UN definition of youth); Participants must have an elevated score on internalizing (depression/anxiety) or externalizing (aggression/ hostility) on a measure validated for use in Sierra Leone; Participants must report some impairment in daily functioning as a result of emotional or behavior problems based on a series of questions adapted from the WHODAS; and Participants must neither be enrolled in school nor have gainful employment of 20 or more hours of work per week over the past four weeks. Exclusion Criteria: Participant fails to meet the age requirements; Participant is either currently enrolled in school or has gainful employment of 20 hours or more of work per week over the past four weeks; Participant is not in favor of joining an employment program; Participants does not have an elevated score on internalizing (depression/anxiety) or externalizing (aggression/ hostility) on a measure validated for use in Sierra Leone; Participant does not report some impairment in daily functioning as a result of emotional or behavior problems based on a series of questions adapted from the WHODAS; Participant identified by clinical staff as: (a) experiencing suicidality, or (b) psychosis. Participants at risk of harm to themselves or others, as well as those requiring treatment beyond the scope of YRI will be referred to local mental health or social work treatment facilitates as appropriate.
Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 24 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YRI + Employment Program<br>Immediately following enrollment participants will complete the YRI intervention, followed by an income generating activity program. | Behavioral: YRI<br>* Youth Readiness Intervention (YRI) is an innovative, evidence-based mental health intervention to address co-morbid difficulties with externalizing problems (anger/emotion dysregulation) and internalizing problems (hopelessness/anxiety) among violence-affected youth. YRI methodology draws on evidence-based treatment elements commonly used in both cognitive-behavioral intervention and group interpersonal therapy. YRI has cross-cutting efficacy across a range of mental health conditions common in violence-affected youth. YRI will be delivered in 12 sessions over the course of 3 months.<br>* Other names: Youth Readiness Intervention;Other: Income generating activity program<br>* Income generating activity programming will be carried out by GOAL in partnership with St. George's foundation through use of their current funding. GOAL focuses on supporting people in need by providing healthcare resources, advocating and advancing child protection practices and policies, and administering livelihood programs to empower them improve their lives in a sustainable manner. The St. George's Foundation's addresses child welfare concerns by actively reaching out to homeless and orphaned children. The program is 4 months in length and consists of skills training, soft skills development (primarily in numeracy and literacy), and a cash transfer of $200.<br>|
| Experimental: Employment Program<br>Immediately following enrollment participants will complete an income generating activity program. | Other: Income generating activity program<br>* Income generating activity programming will be carried out by GOAL in partnership with St. George's foundation through use of their current funding. GOAL focuses on supporting people in need by providing healthcare resources, advocating and advancing child protection practices and policies, and administering livelihood programs to empower them improve their lives in a sustainable manner. The St. George's Foundation's addresses child welfare concerns by actively reaching out to homeless and orphaned children. The program is 4 months in length and consists of skills training, soft skills development (primarily in numeracy and literacy), and a cash transfer of $200.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in % of youth with improved health outcomes | The percent of youth with improved mental health and daily functioning will be measured through a quantitative assessment battery including measurements from the Hopkins Symptoms Checklist, Oxford Measure of Psychosocial Adjustment, Ways of Coping Questionnaire, UCLA Traumatic Stress Disorder Reaction Index, World Health Organization Disability Adjustment Scale, Difficulties in Emotion Regulation Scale. | Baseline, 3 months, 6 months, and 12 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| YRI Fidelity Protocol | Feedback will be gained on the more or less successful programmatic mechanisms and the intervention quality and sustainability through semi-structured qualitative exit interviews with interventionists and youth. | 3 months |
| Change in knowledge, attitudes, and behaviors of youth around employment and access to employment services. | Supervisors will assess youth on attendance, workplace performance, economic self-sufficiency, financial consumption/expenditures, savings and employment-related behaviors (supervisors will be interviewed about each young person blind to their group assignment). | 6 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
War, Depression/therapy, Developing Countries, Interpersonal Relations, Life Change Events, Psychotherapy, group, Resilience, Psychological, Sierra Leone, Survivors/psychology, Social Adjustment, Social Behavior
|
NCT04564976
|
Social Support and Reduced Fear Acquisition
|
University of California, Los Angeles researchers will recruit healthy participants and anxious participants (those diagnosed with social anxiety disorder) age 18-55 years old to participate in a study examining whether the ability of social support figure reminders to prevent the acquisition of fear in healthy participants extends to those with anxiety disorders.~After being recruited from the UCLA community (healthy participants, n = 50) or referred by treatment providers at the Anxiety and Depression Research Center at UCLA (anxious participants, n =50) and undergoing a telephone screening and in-person screening, 100 participants will be enrolled in the study. During the experiment, all participants will undergo the same procedures: undergoing fear acquisition procedures--the repeated pairing of a neutral image with a mild electric shock that ultimately leads to the association of threat of shock with the image--in the presence of an image of a social support figure (provided by participants) and an image of a smiling stranger.
|
Can Social Support Figures Enhance Fear Extinction in Patients With Social Anxiety?
|
Fear, Anxiety
|
* Behavioral: Social support image
|
Inclusion Criteria:~healthy adults 18 and 35~fluent in English~no history of mental illness (healthy participants: including anxiety, depression, phobia, or any other mental health related disorder diagnosed by a mental health professional)~diagnosis of social anxiety disorder (anxious participants: allowed co-morbid disorders include depression, other anxiety disorders, and PTSD)~Exclusion Criteria:~pregnant or planning to become pregnant during the experiment period~presence of chronic mental illness (healthy participants: as determined by the report of a past diagnosis of mental illness by a physician or psychologist and/or the prescription of medication related to mental health disorder; including anxiety, depression, phobia, or any other diagnosed psychological disorder)~presence of non-allowed co-morbid disorders (anxious participants: including, bipolar disorder, psychosis, substance use disorder, neurological disorder, and/or obsessive-compulsive disorder)~current and regular use of prescription medications related to mental health disorders
|
18 Years
|
55 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fear response during acquisition indicated by elevated Galvanic Skin Response (GSR) | presence of fear response as indicated by significantly higher galvanic skin response (GSR: an index of peripheral stress responding) to a previously learned fearful image (CS+) compared to a baseline comparator (CS-: never learned to be fearful). | during acquisition procedure |
| Fear response post-acquisition indicated by elevated GSR | presence of fear response as indicated by significantly higher galvanic skin response (GSR: an index of peripheral stress responding) to a previously learned fearful image (CS+) compared to a baseline comparator (CS-: never learned to be fearful). | same session - directly post-acquisition (approximately 5 minutes post procedure) |
|
social support, fear acquisition
|
Anxiety Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Social Support<br> | Behavioral: Social support image<br>* An image of a social support figure specific to each participant (provided by the participant) will be present while participants undergo a fear acquisition procedure. Specifically--the image will be presented alongside a neutral image that is either consistently paired with shock (CS+) or never paired with shock (CS-), so that assessment of whether there are differences in fear responding (evaluated via SCR) due the shock pairing can be assessed. This is a typical fear acquisition procedure, and a typical outcome would be for SCR to be higher for the CS+ compared to the CS- toward the end and following the procedure, indicating that the CS+ is now associated with the aversive shock and is bringing about a fear response (in this case indexed by increased sympathetic nervous system activity preparing the body to fight or flee).<br>|
|
Social Support and Reduced Fear Acquisition
Study Overview
=================
Brief Summary
-----------------
University of California, Los Angeles researchers will recruit healthy participants and anxious participants (those diagnosed with social anxiety disorder) age 18-55 years old to participate in a study examining whether the ability of social support figure reminders to prevent the acquisition of fear in healthy participants extends to those with anxiety disorders. After being recruited from the UCLA community (healthy participants, n = 50) or referred by treatment providers at the Anxiety and Depression Research Center at UCLA (anxious participants, n =50) and undergoing a telephone screening and in-person screening, 100 participants will be enrolled in the study. During the experiment, all participants will undergo the same procedures: undergoing fear acquisition procedures--the repeated pairing of a neutral image with a mild electric shock that ultimately leads to the association of threat of shock with the image--in the presence of an image of a social support figure (provided by participants) and an image of a smiling stranger.
Official Title
-----------------
Can Social Support Figures Enhance Fear Extinction in Patients With Social Anxiety?
Conditions
-----------------
Fear, Anxiety
Intervention / Treatment
-----------------
* Behavioral: Social support image
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: healthy adults 18 and 35 fluent in English no history of mental illness (healthy participants: including anxiety, depression, phobia, or any other mental health related disorder diagnosed by a mental health professional) diagnosis of social anxiety disorder (anxious participants: allowed co-morbid disorders include depression, other anxiety disorders, and PTSD) Exclusion Criteria: pregnant or planning to become pregnant during the experiment period presence of chronic mental illness (healthy participants: as determined by the report of a past diagnosis of mental illness by a physician or psychologist and/or the prescription of medication related to mental health disorder; including anxiety, depression, phobia, or any other diagnosed psychological disorder) presence of non-allowed co-morbid disorders (anxious participants: including, bipolar disorder, psychosis, substance use disorder, neurological disorder, and/or obsessive-compulsive disorder) current and regular use of prescription medications related to mental health disorders
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Social Support<br> | Behavioral: Social support image<br>* An image of a social support figure specific to each participant (provided by the participant) will be present while participants undergo a fear acquisition procedure. Specifically--the image will be presented alongside a neutral image that is either consistently paired with shock (CS+) or never paired with shock (CS-), so that assessment of whether there are differences in fear responding (evaluated via SCR) due the shock pairing can be assessed. This is a typical fear acquisition procedure, and a typical outcome would be for SCR to be higher for the CS+ compared to the CS- toward the end and following the procedure, indicating that the CS+ is now associated with the aversive shock and is bringing about a fear response (in this case indexed by increased sympathetic nervous system activity preparing the body to fight or flee).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fear response during acquisition indicated by elevated Galvanic Skin Response (GSR) | presence of fear response as indicated by significantly higher galvanic skin response (GSR: an index of peripheral stress responding) to a previously learned fearful image (CS+) compared to a baseline comparator (CS-: never learned to be fearful). | during acquisition procedure |
| Fear response post-acquisition indicated by elevated GSR | presence of fear response as indicated by significantly higher galvanic skin response (GSR: an index of peripheral stress responding) to a previously learned fearful image (CS+) compared to a baseline comparator (CS-: never learned to be fearful). | same session - directly post-acquisition (approximately 5 minutes post procedure) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
social support, fear acquisition
|
||
NCT05089981
|
Intravenous NAC Use in ACLF Patients
|
Primary Objective To evaluate the efficacy and safety of 72 hour NAC treatment regimen in the management of ACLF~Secondary Objective To evaluate the six weeks mortality and length of hospital stay in ACLF patients treated with NAC~Randomized, Double blind pilot study of IV N-Acetyl cysteine for the treatment of ACLF. Participants will be randomized into intervention and control arm using block randomization by computer generated random numbers. Efficacy will be assessed by clinical improvement in symptoms and signs of decompensated chronic liver disease (CLD). To assess safety degree of adverse reactions will be observed. Periodic assessments until 28 day will be done consisting of Physical exam, safety assessments, vital signs and lab tests.~Dose of Drug: 72 hour regimen consisting of three doses of intravenous N-Acetyl cysteine will be used for a total dose of 300mg/kg.~Number of Patients: 100 Accrual period: 15 months
|
Introduction:~Acute on Chronic Liver Failure (ACLF) is a relatively new entity, characterized by complications of cirrhosis and high rate of organ failures. Short term mortality at 28 days is high (>15%). ACLF is multifactorial in its etiology and there is no consensus about the definitions between different parts of the world. The Asian Pacific Association for the Study of the Liver (APASL) consensus defines ACLF as Acute hepatic insult manifesting as jaundice (serum bilirubin ≥ 5mg/dl and coagulopathy (INR≥1.5 or prothrombin activity <40% complicated within 4 weeks by clinical ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease or cirrhosis, and is associated with a high 28-day day mortality. Another definition of ACLF defines it as an acute deterioration of pre-existing chronic liver disease, usually related to a precipitating event and associated with increased mortality at 3 months due to multi-system organ failure. This definition also includes a high mortality at 28 days and organ failures.~Events known to precipitate ACLF include Acute alcoholic hepatitis, acute hepatotrophic viral infections , reactivation of hepatitis B virus infection, Drug induced liver injury (DILI), Gastrointestinal bleeding, sepsis, ischemia to the liver and portal vein thrombosis.~An enhanced pro-inflammatory cytokine environment has been shown to be present in ACLF. These are chronically primed neutrophils which are energy depleted and unable to carry out the phagocytosis function, leading to a functional failure in combating infections.~Cytokines also play a key role in the pathogenesis of the inflammatory response. Elevated serum levels of TNF-α, sTNF-αR1, sTNF-αR2, interleukin (IL)-2, IL-2R, IL-4, IL-6, IL-6,IL-8, IL-10 and interferon-γ have been described. Raised levels of these pro-inflammatory cytokines can be due to necrotic liver cells, reduced clearance by the liver or most importantly, from activation of toll-like receptors (TLRs). These receptors activate Kupffer cells (KCs), which play a key role I the pathogenesis of liver injury by activating signaling cascades, transcription of pro-inflammatory cytokines and super oxide agents. The resulting oxidative stress releases proteolytic enzymes and vasoactive substances like endothelin-1 (ET-1), thromboxane A2, nitric oxide (NO), and prostaglandins which lead to microcirculatory dysfunction. The entire cascade ultimately results in hepatocyte death and liver dysfunction.~The reactive oxygen species (ROS) released by kupffer cells activate hepatic stellate cells (HSCs) leading to increased synthesis of extracellular matrix (ECM). Oxidative stress (OS) leads to worsening inflammation, focal and zonal necrosis in the liver and thus architectural distortion. Several studies relating to liver diseases indicate an over production of ROS and/or reduction of hepatic Gutathione (GSH) which is the most abundant cellular anti-oxidant, which exhibits numerous and versatile functions and therefore protects cells against toxicity regardless of etiology of disease. N-Acetyle cystein (NAC) has an optimal thiol redox state, which helps protective ability of the cell to counter balance OS and inflammation. NAC has been used in a variety of clinical conditions, such as inflammatory bowel disease, pulmonary diseases, cystic fibrosis, septic shock and aceto-aminophen and non-aceto-aminophen induced acute liver failure (ALF). Moreover, it has also been found to improve liver blood flow and liver function in septic shock and non-alcoholic fatty liver disease.~Methodology:~Trial design The study is a randomized double blind placebo controlled pilot trial. Study Settings The trial will be conducted in in-patient units of Aga Khan University Hospital (AKUH) & National Institute of Liver Diseases (NILGID), Dow university Hospital where ACLF patients are admitted. Patients will be followed up for survival six weeks post discharge.~Study population:~Inclusion criteria:~Patients with ACLF having CLIF-C ACLF (Acute-on-Chronic Liver Failure) scores of 35 to 65 will be enrolled in this study.~Establishment of ACLF grade 1-3 according to EASL- CLIFF criteria~Willing to provide informed consent to participate in the study (by study subject or next of kin)~Exclusion criteria:~History of hypersensitivity to NAC~Hepatocellular carcinoma~Pregnancy~Advanced cardiovascular, neurological or pulmonary disease~Subject Screening and Recruitment:~The patients admitted with ACLF at the two sites will be enrolled in this study. Clinical and laboratory criteria will establish the diagnosis of ACLF.~Randomization and Allocation:~Two treatments of A, B and Block size of 2 x 2= 4 Concealed allocation is assured by using of a central web-based system. A double-dummy design would be implemented for subject and study personnel blinding. Blinded assessors will collect outcomes data.~Blinding:~The study will be double blinded to avoid any biases. Participant as well as investigators will be blinded to the intervention assignment. The assignment will be kept in concealed envelopes.~Group I:~Intravenous N-acetylcysteine in standard IV form. Infusion of NAC shall be administered as follows:~72 hour regimen: consists of 3 doses; total dose delivered: 300 mg/kg Loading dose: 150 mg/kg (maximum 15 g) infused over 60 minutes Second dose: 50 mg/kg (max 5g) infused over 4 hours Third dose: 100mg/kg (maximum: 10 g) infused over 67 hours Patients will be monitored for 96 hours post treatment.~Group II:~Patient in this arm will be treated with standard of care and will receive identical placebo in IV form for 72 hours additionally.~Composition: Normal saline with identical color and package~Methods and assessments~Laboratory assessments required:~Complete blood count~Prothrombin time ratio, APTT, INR~Blood urea nitrogen~Serum creatinine levels~Liver function profile including total protein group~Oxygen saturation~Abdominal ultrasound~Albumin~Procalcitonin~CRP~Arterial ammonia~Interleukin-10~TNF- alpha~ABGs~Lactate~Blood random glucose~Oxidized albumin~Subject Compliance Monitoring:~Random checks will be done by the PI and team to ensure protocol compliance.~Study Duration:~The total duration of study is 15 months. Each participant will be follow up to 6 weeks (+/- 7 days). The study will be closed when required number of participants and follow-up time has been completed or participants have documented events.~Discontinuation criteria:~Liver transplant~Death~sever adverse reaction~An interim-analysis will be perform on the primary endpoint when 25% of patients have been randomized and have completed the 6 weeks follow-up~Any SAE which develop within 24 hours of completion of NAC infusion will be considered as treatment emergent.~Safety reporting:~Investigators and study team will be monitor and reporting the adverse event/reaction during the study trial through online pharmacy ADR form~serious adverse events (SAE):~Respectively, any adverse event or adverse reaction that:~results in death~is life-threatening*~requires hospitalisation or prolongation of existing hospitalisation**~results in persistent or significant disability or incapacity~consists of a congenital anomaly or birth defect~other important medical event(s)***~Referrences:~Moreau R, Arroyo Vincente. Acute-on-Chronic Liver Failure: A new clinical entity. Clinical Gastroenterology and Hepatology 2015;13: 836-841~Sarin S et al. Acute-on chronic liver failure:consensus recommendations of the Asia Pacific association for the study of the liver (APASL). Hepatol Int. 2014;8:453-471~Moreau R et al. Acute-on chronic liver failure is a distinct syndrome which develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013;144: 1426-1437~Arroyo V, Moreau R, Lalan R. et al. Acute-0on-chronic liver failure: A new syndrome that will re-classify cirrhosis. J Hepatology 2015;62: S131-S143~Sarin S, Choudhary A, Acute-on-chronic liver failure: terminology, mechanisms and management: Nature reviews: Gastroenterology and Hepatology 2016~Asrani SK, O'Leary JG, Acute-on-chronic liver failure. Clin Liver Dis 2014;18: 561-574~Jalan R, Gines P, Olson JC et al. Acute-on-chronic liver failure. J Hepatol 2012;57:1336-1348~Gustot T. Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response. Curr opin Crit care.2011;17:153-159~Sen S, Davies NA, Mookerjee RP et al. Pathophysiological effect of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study. Liver Transpl 2004;10: 1109-1119~Bilzer M, Roggel F,Gerbes AL, Role of Kupffer cells in host defense and liver disease. Liver Int 2006; 26: 1175-1186 Holland-Fischer P, Gronbaek H, Sandhl TD et al. Kupffer cells are activated in cirrhotic portal hypertension and not normalized by TIPS. Gut 2011;60: 1389-139315 months~The Efficacy and safety of N-acetyl-L-cysteine (NAC) as adjuvant therapy in acute on chronic liver failure (ACLF)~A randomized double blind placebo controlled pilot trial~14. Rockey DC, Fouasier L, Chung JJ, et al. Cellular localization of of endothelin-1 and increased production of liver injury in the rat potential for autocrine and paracrine effects on stellate cells. Hepatology 1998;27: 472-480 15. Diesen DL, Kuo PC, Nitric Oxide and redox regulaton in the liver Part 11. Redox biology in pathologic hepatocytes and implications for intervention. J Surg Res 2011; 167, 96-112 16. Chatterjee R, Mitra A, An overview of effective therapies and recent advances in biomarkers for chronic liver disease and associated cancer. Int. Immunopharmacol 2015; 24: 335-345 17. Mussaco-Sebio R, Saporito-Magrina C,Semprine J et al, J Inorg Biochem 2014; 137: 94-100 18. Okanoue T, Mitsuyoushi H. Non-alcoholic steatohepatitis,oxdative stress and NASH. Nihon Naika Gakkai Zasshi 2006, 95,51-56 19. Kersksick C, Willoughby D, The anti-oxidant role of Glutathione and N-acetylcysteine supplements and exercise induced oxidative stress. J Int Soc Sports Nutrition 2005;9: 38-44 20. Moura FA, de Andrale KQ, Dos Santos JC, et al. Anti-oxidant therapy for the treatment of inBa-Ma pigflammatory bowel disease: Does it work? Redox Biol 2015; 6: 617-639 21. Li J, Zhang S, Wu Y, Protective effects of N-acetylcysteine on the liver of brain dead mini pig. Transplant Proc 2010: 42: 195-199
|
The Efficacy and Safety of N-acetyl-L-cysteine (NAC) as Adjuvant Therapy in Acute on Chronic Liver Failure (ACLF) A Randomized Double Blind Placebo Controlled Pilot Trial
|
Acute on Chronic Liver Failure(ACLF)
|
* Drug: N acetyl cysteine
* Drug: Placebo of N acetyl cysteine
|
Inclusion Criteria:~Criteria for inclusion will be~Age between 18 and 70 years~Establishment of ACLF grade 1-3 according to EASL- CLIFF criteria~Willing to provide informed consent to participate in the study (by study subject or next of kin)~Exclusion Criteria:~Criteria for exclusion will be~History of hypersensitivity to NAC~Hepatocellular carcinoma~pregnancy~Advanced cardiovascular or pulmonary disease~Advanced primary neurological disease (such as stroke)
|
18 Years
|
70 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double Blind Placebo Controlled
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy & safety of NAC in the improvement of ACLF To evaluate the efficacy and safety of 72 hour NAC treatment regimen in the management of ACLF | clinical and biochemical improvement will be noted as NAC efficacy and safety through AE & SAE | 72 hrs |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-weeks Survival | A 6-weeks survival data will be collected for this secondary outcome measure | 6 weeks |
| Length of hospital stay | Length of hospital stay in patients treated with NAC Vs Placebo | 6 weeks |
|
Antidotes, Acetylcysteine, N-monoacetylcystine, Antiviral Agents, Anti-Infective Agents, Expectorants, Respiratory System Agents, Free Radical Scavengers, Antioxidants, Molecular Mechanisms of Pharmacological Action, Protective Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NAC group<br>IV N acetyl cysteine 300mg will be administered in doses as described in protocol | Drug: N acetyl cysteine<br>* Intravenous use of N acetyl cysteine in prescribed doses<br>|
| Placebo Comparator: NAC Placebo group<br>IV Placebo of N acetyl cysteine will be administered in doses as described in protocol (Placebo will be normal saline in a look alike preparation with same volume as active NAC arm) | Drug: Placebo of N acetyl cysteine<br>* Intravenous Placebo of N Acetyl cysteine in look alike form (Normal saline)<br>|
|
Intravenous NAC Use in ACLF Patients
Study Overview
=================
Brief Summary
-----------------
Primary Objective To evaluate the efficacy and safety of 72 hour NAC treatment regimen in the management of ACLF Secondary Objective To evaluate the six weeks mortality and length of hospital stay in ACLF patients treated with NAC Randomized, Double blind pilot study of IV N-Acetyl cysteine for the treatment of ACLF. Participants will be randomized into intervention and control arm using block randomization by computer generated random numbers. Efficacy will be assessed by clinical improvement in symptoms and signs of decompensated chronic liver disease (CLD). To assess safety degree of adverse reactions will be observed. Periodic assessments until 28 day will be done consisting of Physical exam, safety assessments, vital signs and lab tests. Dose of Drug: 72 hour regimen consisting of three doses of intravenous N-Acetyl cysteine will be used for a total dose of 300mg/kg. Number of Patients: 100 Accrual period: 15 months
Detailed Description
-----------------
Introduction: Acute on Chronic Liver Failure (ACLF) is a relatively new entity, characterized by complications of cirrhosis and high rate of organ failures. Short term mortality at 28 days is high (>15%). ACLF is multifactorial in its etiology and there is no consensus about the definitions between different parts of the world. The Asian Pacific Association for the Study of the Liver (APASL) consensus defines ACLF as Acute hepatic insult manifesting as jaundice (serum bilirubin ≥ 5mg/dl and coagulopathy (INR≥1.5 or prothrombin activity <40% complicated within 4 weeks by clinical ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease or cirrhosis, and is associated with a high 28-day day mortality. Another definition of ACLF defines it as an acute deterioration of pre-existing chronic liver disease, usually related to a precipitating event and associated with increased mortality at 3 months due to multi-system organ failure. This definition also includes a high mortality at 28 days and organ failures. Events known to precipitate ACLF include Acute alcoholic hepatitis, acute hepatotrophic viral infections , reactivation of hepatitis B virus infection, Drug induced liver injury (DILI), Gastrointestinal bleeding, sepsis, ischemia to the liver and portal vein thrombosis. An enhanced pro-inflammatory cytokine environment has been shown to be present in ACLF. These are chronically primed neutrophils which are energy depleted and unable to carry out the phagocytosis function, leading to a functional failure in combating infections. Cytokines also play a key role in the pathogenesis of the inflammatory response. Elevated serum levels of TNF-α, sTNF-αR1, sTNF-αR2, interleukin (IL)-2, IL-2R, IL-4, IL-6, IL-6,IL-8, IL-10 and interferon-γ have been described. Raised levels of these pro-inflammatory cytokines can be due to necrotic liver cells, reduced clearance by the liver or most importantly, from activation of toll-like receptors (TLRs). These receptors activate Kupffer cells (KCs), which play a key role I the pathogenesis of liver injury by activating signaling cascades, transcription of pro-inflammatory cytokines and super oxide agents. The resulting oxidative stress releases proteolytic enzymes and vasoactive substances like endothelin-1 (ET-1), thromboxane A2, nitric oxide (NO), and prostaglandins which lead to microcirculatory dysfunction. The entire cascade ultimately results in hepatocyte death and liver dysfunction. The reactive oxygen species (ROS) released by kupffer cells activate hepatic stellate cells (HSCs) leading to increased synthesis of extracellular matrix (ECM). Oxidative stress (OS) leads to worsening inflammation, focal and zonal necrosis in the liver and thus architectural distortion. Several studies relating to liver diseases indicate an over production of ROS and/or reduction of hepatic Gutathione (GSH) which is the most abundant cellular anti-oxidant, which exhibits numerous and versatile functions and therefore protects cells against toxicity regardless of etiology of disease. N-Acetyle cystein (NAC) has an optimal thiol redox state, which helps protective ability of the cell to counter balance OS and inflammation. NAC has been used in a variety of clinical conditions, such as inflammatory bowel disease, pulmonary diseases, cystic fibrosis, septic shock and aceto-aminophen and non-aceto-aminophen induced acute liver failure (ALF). Moreover, it has also been found to improve liver blood flow and liver function in septic shock and non-alcoholic fatty liver disease. Methodology: Trial design The study is a randomized double blind placebo controlled pilot trial. Study Settings The trial will be conducted in in-patient units of Aga Khan University Hospital (AKUH) & National Institute of Liver Diseases (NILGID), Dow university Hospital where ACLF patients are admitted. Patients will be followed up for survival six weeks post discharge. Study population: Inclusion criteria: Patients with ACLF having CLIF-C ACLF (Acute-on-Chronic Liver Failure) scores of 35 to 65 will be enrolled in this study. Establishment of ACLF grade 1-3 according to EASL- CLIFF criteria Willing to provide informed consent to participate in the study (by study subject or next of kin) Exclusion criteria: History of hypersensitivity to NAC Hepatocellular carcinoma Pregnancy Advanced cardiovascular, neurological or pulmonary disease Subject Screening and Recruitment: The patients admitted with ACLF at the two sites will be enrolled in this study. Clinical and laboratory criteria will establish the diagnosis of ACLF. Randomization and Allocation: Two treatments of A, B and Block size of 2 x 2= 4 Concealed allocation is assured by using of a central web-based system. A double-dummy design would be implemented for subject and study personnel blinding. Blinded assessors will collect outcomes data. Blinding: The study will be double blinded to avoid any biases. Participant as well as investigators will be blinded to the intervention assignment. The assignment will be kept in concealed envelopes. Group I: Intravenous N-acetylcysteine in standard IV form. Infusion of NAC shall be administered as follows: 72 hour regimen: consists of 3 doses; total dose delivered: 300 mg/kg Loading dose: 150 mg/kg (maximum 15 g) infused over 60 minutes Second dose: 50 mg/kg (max 5g) infused over 4 hours Third dose: 100mg/kg (maximum: 10 g) infused over 67 hours Patients will be monitored for 96 hours post treatment. Group II: Patient in this arm will be treated with standard of care and will receive identical placebo in IV form for 72 hours additionally. Composition: Normal saline with identical color and package Methods and assessments Laboratory assessments required: Complete blood count Prothrombin time ratio, APTT, INR Blood urea nitrogen Serum creatinine levels Liver function profile including total protein group Oxygen saturation Abdominal ultrasound Albumin Procalcitonin CRP Arterial ammonia Interleukin-10 TNF- alpha ABGs Lactate Blood random glucose Oxidized albumin Subject Compliance Monitoring: Random checks will be done by the PI and team to ensure protocol compliance. Study Duration: The total duration of study is 15 months. Each participant will be follow up to 6 weeks (+/- 7 days). The study will be closed when required number of participants and follow-up time has been completed or participants have documented events. Discontinuation criteria: Liver transplant Death sever adverse reaction An interim-analysis will be perform on the primary endpoint when 25% of patients have been randomized and have completed the 6 weeks follow-up Any SAE which develop within 24 hours of completion of NAC infusion will be considered as treatment emergent. Safety reporting: Investigators and study team will be monitor and reporting the adverse event/reaction during the study trial through online pharmacy ADR form serious adverse events (SAE): Respectively, any adverse event or adverse reaction that: results in death is life-threatening* requires hospitalisation or prolongation of existing hospitalisation** results in persistent or significant disability or incapacity consists of a congenital anomaly or birth defect other important medical event(s)*** Referrences: Moreau R, Arroyo Vincente. Acute-on-Chronic Liver Failure: A new clinical entity. Clinical Gastroenterology and Hepatology 2015;13: 836-841 Sarin S et al. Acute-on chronic liver failure:consensus recommendations of the Asia Pacific association for the study of the liver (APASL). Hepatol Int. 2014;8:453-471 Moreau R et al. Acute-on chronic liver failure is a distinct syndrome which develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013;144: 1426-1437 Arroyo V, Moreau R, Lalan R. et al. Acute-0on-chronic liver failure: A new syndrome that will re-classify cirrhosis. J Hepatology 2015;62: S131-S143 Sarin S, Choudhary A, Acute-on-chronic liver failure: terminology, mechanisms and management: Nature reviews: Gastroenterology and Hepatology 2016 Asrani SK, O'Leary JG, Acute-on-chronic liver failure. Clin Liver Dis 2014;18: 561-574 Jalan R, Gines P, Olson JC et al. Acute-on-chronic liver failure. J Hepatol 2012;57:1336-1348 Gustot T. Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response. Curr opin Crit care.2011;17:153-159 Sen S, Davies NA, Mookerjee RP et al. Pathophysiological effect of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study. Liver Transpl 2004;10: 1109-1119 Bilzer M, Roggel F,Gerbes AL, Role of Kupffer cells in host defense and liver disease. Liver Int 2006; 26: 1175-1186 Holland-Fischer P, Gronbaek H, Sandhl TD et al. Kupffer cells are activated in cirrhotic portal hypertension and not normalized by TIPS. Gut 2011;60: 1389-139315 months The Efficacy and safety of N-acetyl-L-cysteine (NAC) as adjuvant therapy in acute on chronic liver failure (ACLF) A randomized double blind placebo controlled pilot trial 14. Rockey DC, Fouasier L, Chung JJ, et al. Cellular localization of of endothelin-1 and increased production of liver injury in the rat potential for autocrine and paracrine effects on stellate cells. Hepatology 1998;27: 472-480 15. Diesen DL, Kuo PC, Nitric Oxide and redox regulaton in the liver Part 11. Redox biology in pathologic hepatocytes and implications for intervention. J Surg Res 2011; 167, 96-112 16. Chatterjee R, Mitra A, An overview of effective therapies and recent advances in biomarkers for chronic liver disease and associated cancer. Int. Immunopharmacol 2015; 24: 335-345 17. Mussaco-Sebio R, Saporito-Magrina C,Semprine J et al, J Inorg Biochem 2014; 137: 94-100 18. Okanoue T, Mitsuyoushi H. Non-alcoholic steatohepatitis,oxdative stress and NASH. Nihon Naika Gakkai Zasshi 2006, 95,51-56 19. Kersksick C, Willoughby D, The anti-oxidant role of Glutathione and N-acetylcysteine supplements and exercise induced oxidative stress. J Int Soc Sports Nutrition 2005;9: 38-44 20. Moura FA, de Andrale KQ, Dos Santos JC, et al. Anti-oxidant therapy for the treatment of inBa-Ma pigflammatory bowel disease: Does it work? Redox Biol 2015; 6: 617-639 21. Li J, Zhang S, Wu Y, Protective effects of N-acetylcysteine on the liver of brain dead mini pig. Transplant Proc 2010: 42: 195-199
Official Title
-----------------
The Efficacy and Safety of N-acetyl-L-cysteine (NAC) as Adjuvant Therapy in Acute on Chronic Liver Failure (ACLF) A Randomized Double Blind Placebo Controlled Pilot Trial
Conditions
-----------------
Acute on Chronic Liver Failure(ACLF)
Intervention / Treatment
-----------------
* Drug: N acetyl cysteine
* Drug: Placebo of N acetyl cysteine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Criteria for inclusion will be Age between 18 and 70 years Establishment of ACLF grade 1-3 according to EASL- CLIFF criteria Willing to provide informed consent to participate in the study (by study subject or next of kin) Exclusion Criteria: Criteria for exclusion will be History of hypersensitivity to NAC Hepatocellular carcinoma pregnancy Advanced cardiovascular or pulmonary disease Advanced primary neurological disease (such as stroke)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double Blind Placebo Controlled
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NAC group<br>IV N acetyl cysteine 300mg will be administered in doses as described in protocol | Drug: N acetyl cysteine<br>* Intravenous use of N acetyl cysteine in prescribed doses<br>|
| Placebo Comparator: NAC Placebo group<br>IV Placebo of N acetyl cysteine will be administered in doses as described in protocol (Placebo will be normal saline in a look alike preparation with same volume as active NAC arm) | Drug: Placebo of N acetyl cysteine<br>* Intravenous Placebo of N Acetyl cysteine in look alike form (Normal saline)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy & safety of NAC in the improvement of ACLF To evaluate the efficacy and safety of 72 hour NAC treatment regimen in the management of ACLF | clinical and biochemical improvement will be noted as NAC efficacy and safety through AE & SAE | 72 hrs |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-weeks Survival | A 6-weeks survival data will be collected for this secondary outcome measure | 6 weeks |
| Length of hospital stay | Length of hospital stay in patients treated with NAC Vs Placebo | 6 weeks |
|
|
NCT01477593
|
Circumcision With a Novel Disposable Device in Chinese Children: a Hospital-based Randomized Controlled Trail
|
Circumcision, a removal of the foreskin, is performed commonly at any age in male worldwide. Globally over 25% of men are circumcised. In the Middle East, circumcision is even performed routinely in every male newborn. The benefits from it vastly outweigh the risks. Gradually, more and more Chinese male are willing to undergo it with themselves and their sons. But there are also some complications with circumcision, such as pain, edema, infection, and hemorrhage. Considering of that, physicians continually manage to improve their surgical methods and analgesic techniques.~In the study of Peng, a disposable minimally invasive circumcision anastomosis device named Shenghuan (China Wuhu Snnda Medical Treatment Application Technology Co. Ltd.) (ShD) was introduced to be applied in circumcision. And they concluded that method was quicker, safer and less pain than the conventional techniques of incision. In present study, we carry out a randomized controlled trail, using a different method as Peng introduced with this device in children's circumcision (Yan's), compared with the method as Peng used and the conventional technique in our hospital, and then observe the outcomes.
| null |
Circumcision
|
* Procedure: circumcision with Shenghuan in Yan's method
* Procedure: circumcision with Shenghuan in Peng's method
* Procedure: conventional method with incision
|
Inclusion Criteria:~Children with phimosis or redundant prepuce~Exclusion Criteria:~Children with genital tract infection or deformity,~congenital diseases,~hematological diseases,~or other general diseases
|
3 Years
|
11 Years
|
Male
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| operation time | | within operation |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain score | | within operation |
|
circumcision, chinese children, pain
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I<br> | Procedure: circumcision with Shenghuan in Yan's method<br>* The foreskin is first separated from the glans.Then the inner ring is placed between them and over the glans. After adjusting the position of inner ring to retain 0.5cm inner foreskin, the operator install the outer ring over the foreskin and combine them together. Removal of excess foreskin is then performed upon the device.<br>|
| Active Comparator: Group II<br> | Procedure: circumcision with Shenghuan in Peng's method<br>* The foreskin is first separated from the glans. Then the inner ring is placed on the outer layer of foreskin. Next, the rim of the foreskin is clamped with blood vessel forceps at the 3, 6, 9 and 12 o'clock points. An urologist and an assistant each hold two clamps to widen the opening of the foreskin, and pull it over the inner ring. After the inner and outer layers of the foreskin and the frenulum are symmetrically positioned, the assistant install the outer ring over the foreskin and gently combine it together. Removal of excess foreskin is then performed below the device.<br>|
| Active Comparator: Group III<br> | Procedure: conventional method with incision<br>* The procedure of conventional circumcision involve transection of the excess foreskin with reservation of 0.5cm inner foreskin, haemostasis by electrocautery and suture of skin edges with 4-0 absorption sutures.<br>|
|
Circumcision With a Novel Disposable Device in Chinese Children: a Hospital-based Randomized Controlled Trail
Study Overview
=================
Brief Summary
-----------------
Circumcision, a removal of the foreskin, is performed commonly at any age in male worldwide. Globally over 25% of men are circumcised. In the Middle East, circumcision is even performed routinely in every male newborn. The benefits from it vastly outweigh the risks. Gradually, more and more Chinese male are willing to undergo it with themselves and their sons. But there are also some complications with circumcision, such as pain, edema, infection, and hemorrhage. Considering of that, physicians continually manage to improve their surgical methods and analgesic techniques. In the study of Peng, a disposable minimally invasive circumcision anastomosis device named Shenghuan (China Wuhu Snnda Medical Treatment Application Technology Co. Ltd.) (ShD) was introduced to be applied in circumcision. And they concluded that method was quicker, safer and less pain than the conventional techniques of incision. In present study, we carry out a randomized controlled trail, using a different method as Peng introduced with this device in children's circumcision (Yan's), compared with the method as Peng used and the conventional technique in our hospital, and then observe the outcomes.
Conditions
-----------------
Circumcision
Intervention / Treatment
-----------------
* Procedure: circumcision with Shenghuan in Yan's method
* Procedure: circumcision with Shenghuan in Peng's method
* Procedure: conventional method with incision
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children with phimosis or redundant prepuce Exclusion Criteria: Children with genital tract infection or deformity, congenital diseases, hematological diseases, or other general diseases
Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 11 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I<br> | Procedure: circumcision with Shenghuan in Yan's method<br>* The foreskin is first separated from the glans.Then the inner ring is placed between them and over the glans. After adjusting the position of inner ring to retain 0.5cm inner foreskin, the operator install the outer ring over the foreskin and combine them together. Removal of excess foreskin is then performed upon the device.<br>|
| Active Comparator: Group II<br> | Procedure: circumcision with Shenghuan in Peng's method<br>* The foreskin is first separated from the glans. Then the inner ring is placed on the outer layer of foreskin. Next, the rim of the foreskin is clamped with blood vessel forceps at the 3, 6, 9 and 12 o'clock points. An urologist and an assistant each hold two clamps to widen the opening of the foreskin, and pull it over the inner ring. After the inner and outer layers of the foreskin and the frenulum are symmetrically positioned, the assistant install the outer ring over the foreskin and gently combine it together. Removal of excess foreskin is then performed below the device.<br>|
| Active Comparator: Group III<br> | Procedure: conventional method with incision<br>* The procedure of conventional circumcision involve transection of the excess foreskin with reservation of 0.5cm inner foreskin, haemostasis by electrocautery and suture of skin edges with 4-0 absorption sutures.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| operation time | | within operation |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain score | | within operation |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
circumcision, chinese children, pain
|
||
NCT02416076
|
Ultherapy® for Treating the Face and Neck Using Standard Versus Simulines Transducers
|
Up to 40 participants will be enrolled, randomized and treated. Enrolled participants will receive one, split-face Ulthera® treatment on the face and neck using a Ulthera System standard transducer on one side of the face and a Ulthera System prototype simulines transducers on the other side of the face. Follow-up visits will occur at 90 and 180 days post-treatment. Study images will be obtained pre-treatment, immediately post-treatment, and at each follow-up visit.
|
This is a prospective, multi-center, split-face, randomized pilot trial to determine the clinical feasibility of the Ulthera System prototype simulines transducers, that is, transducers which deliver two lines of treatment simultaneously (at once), in comparison to the standard transducers which deliver a single treatment line, by collecting average pain scores in the treated regions, as well as efficacy and treatment efficiency data. There will be 3 study arms with each arm having 2 treatment groups. Enrolled participants will be randomized to one of two study arms, and one of two treatment groups within each study arm.to determine which side of the face will be treated with Ulthera System standard transducers and Ulthera System prototype simulines transducers and the energy level for treatment. Participants will receive one dual-depth treatment at 4.5 millimeter (mm) and 3.0mm depths.~Clinical feasibility will be assessed based on comfort level of standard transducers versus simulines transducers by comparing average pain scores obtained during study treatment. Efficacy will be determined based on qualitative masked assessment of post-treatment photographs compared to pre-treatment photographs and quantitative eyebrow lift measurements. Patient satisfaction questionnaires will be obtained.
|
Evaluation of the Ulthera® System for Lifting and Tightening the Face and Neck Using Standard Transducers Versus Simulines Transducers
|
Skin Laxity
|
* Device: Ulthera Treatment at EL2
* Device: Ulthera Treatment at EL4
|
Inclusion Criteria:~Male or female, age 30 to 65 years.~Participant in good health.~Skin laxity on the area(s) to be treated.~Understands and accepts the obligation not to undergo any other procedures in the areas to be treated through the follow-up period.~Willingness and ability to comply with protocol requirements, including returning for follow-up visits and abstaining from exclusionary procedures for the duration of the study.~Participants of childbearing potential must have a negative urine pregnancy test result and must not be lactating at the Screening Visit and be willing and able to use an acceptable method of birth control (example barrier methods used with a spermicidal agent, hormonal methods, intrauterine device (IUD), surgical sterilization, abstinence) during the study. Women will not be considered of childbearing potential if one of the following conditions is documented on the medical history:~Postmenopausal for at least 12 months prior to study;~Without a uterus and/or both ovaries; or~Bilateral tubal ligation at least six months prior to study enrollment.~Absence of physical or psychological conditions unacceptable to the investigator.~Willingness to refrain from use of aspirin, Ibuprofen, Naproxen or any other nonsteroidal anti-inflammatory drug (NSAID) prior to each study treatment and chronic use during the entire posttreatment study period. Washout period, if chronic user, for 4 weeks prior to the first treatment. Washout period for limited acute NSAID use, that is, a maximum of 2-3 doses, is required in the 2 weeks prior to any study treatment visit.~Willingness and ability to provide written consent for study-required photography and adherence to photography procedures (that is, removal of jewelry and makeup).~Willingness and ability to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization prior to performance of any study-related procedure.~Exclusion Criteria:~Presence of an active systemic or local skin disease that may affect wound healing.~Severe solar elastosis.~Excessive subcutaneous fat in the area(s) to be treated.~Excessive skin laxity on the area(s) to be treated.~Significant scarring in the area(s) to be treated.~Open wounds or lesions in the area(s) to be treated.~Severe or cystic acne on the area(s) to be treated.~Active implants (example, pacemakers or defibrillators), or metallic implants in the treatment areas (dental implants not included).~Inability to understand the protocol or to give informed consent.~Microdermabrasion, or prescription level glycolic acid treatment to the treatment area(s) within two weeks prior to study participation or during the study.~Marked asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin in the area(s) to be treated.~BMI equal to or greater than 25.~History of chronic drug or alcohol abuse.~History of autoimmune disease.~Concurrent therapy that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study device.~Participants who anticipate the need for surgery or overnight hospitalization during the study.~Participants who, in the investigator's opinion, have a history of poor cooperation, noncompliance with medical treatment, or unreliability.~Concurrent enrollment in any study involving the use of investigational devices or drugs.~Current smoker or history of smoking in the last five years.~Current user of any nicotine-containing products, example, electronic cigarettes (e-cigarettes), Nicorette gum, nicotine patches, etc.~History of the following cosmetic treatments in the area(s) to be treated:~Skin tightening procedure within the past year;~Injectable filler of any type within the past:~i.12 months for Hyaluronic acid fillers (example Rstylane)~ii.12 months for Ca Hydroxyapatite fillers (example Radiesse)~iii. 24 months for Poly-L-Lactic acid fillers (example Sculptra)~iv. Ever for permanent fillers (example Silicone, ArteFill)~c. Neurotoxins within the past six months; d. Ablative resurfacing laser treatment; e. Nonablative, rejuvenative laser or light treatment within the past six months; f. Surgical dermabrasion or deep facial peels; g. Facelifts, blepharoplasty, or browlift within the past 18 months; or h. Any history of contour threads.~History of using the following prescription medications:~Accutane or other systemic retinoids within the past six months;~Topical Retinoids within the past two weeks;~Antiplatelet agents/Anticoagulants (Coumadin, Heparin, Plavix);~Psychiatric drugs that in the investigators opinion would impair the participant from understanding the protocol requirements or understanding and signing the informed consent.
|
30 Years
|
65 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comfort level of standard transducers versus simulines transducers during Ultherapy® treatment | Subjects' treatment-related pain scores will be obtained using a validated 0-10 point Numeric Rating Scale while study treatment is being administered. It is estimated that each study treatment will be completed in approximately 90 minutes. | During study treatment. Participants will be followed for an average of 90 minutes. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brow lift obtained using simulines versus standard transducers | Brow lift as assessed by quantitative measurements of pre- to post-treatment photos. | 90 days post-treatment |
| Brow lift obtained using simulines versus standard transducers | Brow lift as assessed by quantitative measurements of pre- to post-treatment photos. | 180 days post-treatment |
| Improvement in overall lifting and tightening of skin | As assessed by a masked, qualitative assessment of photographs at 90 days post-treatment compared to baseline. | 90 days post-treatment |
| Improvement in overall lifting and tightening of skin | As assessed by a masked, qualitative assessment of photographs at 180 days post-treatment compared to baseline. | 180 days post-treatment |
| Patient Satisfaction | As assessed by a patient satisfaction questionnaire completed by the subject. | 90 days post-treatment |
| Efficiency of simulines versus standard transducers | As determined by comparing treatment times using the simulines transducers compared to treatment times using the standard transducers. | During study treatment |
|
Ulthera® System, Ultherapy®, Ulthera, Inc.
|
Cutis Laxa, Skin Diseases, Genetic, Genetic Diseases, Inborn, Connective Tissue Diseases, Skin Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A - LT side simulines Ulthera treatment at EL2<br>Ulthera treatment using 'Ulthera System, prototype simulines transducers' on the LEFT side of the face and 'Ulthera System, standard transducers' on the RIGHT of the face at the default Energy Level [EL2]. | Device: Ulthera Treatment at EL2<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
| Active Comparator: Group B - RT side simulines Ulthera treatment at EL2<br>Ulthera treatment using 'Ulthera System, prototype simulines transducers' on the RIGHT side of the face and 'Ulthera System, standard transducers' on the LEFT side of the face at the default Energy Level [EL2] . | Device: Ulthera Treatment at EL2<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
| Active Comparator: Group C - LT side simulines Ulthera treatment at EL4<br>Ulthera treatment using 'Ulthera System, prototype simulines transducers' on the LEFT side of the face and 'Ulthera System, standard transducers' on the RIGHT of the face at a higher Energy Level [EL4]. | Device: Ulthera Treatment at EL4<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
| Active Comparator: Group D - RT side simulines Ulthera treatment at EL4<br>Ulthera treatment using 'Ulthera System, prototype simulines transducers' on the RIGHT side of the face and 'Ulthera System, standard transducers' on the LEFT side of the face at a higher Energy Level [EL4] . | Device: Ulthera Treatment at EL4<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
| Active Comparator: Group E - LT side simulines/standard Ulthera treatment at EL4<br>Ulthera treatment using a 4-4.5 'Ulthera System, prototype simulines transducers' and 7-3.0 'Ulthera System, standard transducers' on the LEFT side of the face and 'Ulthera System, standard transducers' on the RIGHT of the face at a higher Energy Level [EL4]. | Device: Ulthera Treatment at EL4<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
| Active Comparator: Group F - RT side simulines/standard Ulthera treatment at EL4<br>Ulthera treatment using a 4-4.5 'Ulthera System, prototype simulines transducers'and 7-3.0 standard transducer on the RIGHT side of the face and 'Ulthera System, standard transducers' on the LEFTof the face at a higher Energy Level [EL4]. | Device: Ulthera Treatment at EL4<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
|
Ultherapy® for Treating the Face and Neck Using Standard Versus Simulines Transducers
Study Overview
=================
Brief Summary
-----------------
Up to 40 participants will be enrolled, randomized and treated. Enrolled participants will receive one, split-face Ulthera® treatment on the face and neck using a Ulthera System standard transducer on one side of the face and a Ulthera System prototype simulines transducers on the other side of the face. Follow-up visits will occur at 90 and 180 days post-treatment. Study images will be obtained pre-treatment, immediately post-treatment, and at each follow-up visit.
Detailed Description
-----------------
This is a prospective, multi-center, split-face, randomized pilot trial to determine the clinical feasibility of the Ulthera System prototype simulines transducers, that is, transducers which deliver two lines of treatment simultaneously (at once), in comparison to the standard transducers which deliver a single treatment line, by collecting average pain scores in the treated regions, as well as efficacy and treatment efficiency data. There will be 3 study arms with each arm having 2 treatment groups. Enrolled participants will be randomized to one of two study arms, and one of two treatment groups within each study arm.to determine which side of the face will be treated with Ulthera System standard transducers and Ulthera System prototype simulines transducers and the energy level for treatment. Participants will receive one dual-depth treatment at 4.5 millimeter (mm) and 3.0mm depths. Clinical feasibility will be assessed based on comfort level of standard transducers versus simulines transducers by comparing average pain scores obtained during study treatment. Efficacy will be determined based on qualitative masked assessment of post-treatment photographs compared to pre-treatment photographs and quantitative eyebrow lift measurements. Patient satisfaction questionnaires will be obtained.
Official Title
-----------------
Evaluation of the Ulthera® System for Lifting and Tightening the Face and Neck Using Standard Transducers Versus Simulines Transducers
Conditions
-----------------
Skin Laxity
Intervention / Treatment
-----------------
* Device: Ulthera Treatment at EL2
* Device: Ulthera Treatment at EL4
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, age 30 to 65 years. Participant in good health. Skin laxity on the area(s) to be treated. Understands and accepts the obligation not to undergo any other procedures in the areas to be treated through the follow-up period. Willingness and ability to comply with protocol requirements, including returning for follow-up visits and abstaining from exclusionary procedures for the duration of the study. Participants of childbearing potential must have a negative urine pregnancy test result and must not be lactating at the Screening Visit and be willing and able to use an acceptable method of birth control (example barrier methods used with a spermicidal agent, hormonal methods, intrauterine device (IUD), surgical sterilization, abstinence) during the study. Women will not be considered of childbearing potential if one of the following conditions is documented on the medical history: Postmenopausal for at least 12 months prior to study; Without a uterus and/or both ovaries; or Bilateral tubal ligation at least six months prior to study enrollment. Absence of physical or psychological conditions unacceptable to the investigator. Willingness to refrain from use of aspirin, Ibuprofen, Naproxen or any other nonsteroidal anti-inflammatory drug (NSAID) prior to each study treatment and chronic use during the entire posttreatment study period. Washout period, if chronic user, for 4 weeks prior to the first treatment. Washout period for limited acute NSAID use, that is, a maximum of 2-3 doses, is required in the 2 weeks prior to any study treatment visit. Willingness and ability to provide written consent for study-required photography and adherence to photography procedures (that is, removal of jewelry and makeup). Willingness and ability to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization prior to performance of any study-related procedure. Exclusion Criteria: Presence of an active systemic or local skin disease that may affect wound healing. Severe solar elastosis. Excessive subcutaneous fat in the area(s) to be treated. Excessive skin laxity on the area(s) to be treated. Significant scarring in the area(s) to be treated. Open wounds or lesions in the area(s) to be treated. Severe or cystic acne on the area(s) to be treated. Active implants (example, pacemakers or defibrillators), or metallic implants in the treatment areas (dental implants not included). Inability to understand the protocol or to give informed consent. Microdermabrasion, or prescription level glycolic acid treatment to the treatment area(s) within two weeks prior to study participation or during the study. Marked asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin in the area(s) to be treated. BMI equal to or greater than 25. History of chronic drug or alcohol abuse. History of autoimmune disease. Concurrent therapy that, in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the study device. Participants who anticipate the need for surgery or overnight hospitalization during the study. Participants who, in the investigator's opinion, have a history of poor cooperation, noncompliance with medical treatment, or unreliability. Concurrent enrollment in any study involving the use of investigational devices or drugs. Current smoker or history of smoking in the last five years. Current user of any nicotine-containing products, example, electronic cigarettes (e-cigarettes), Nicorette gum, nicotine patches, etc. History of the following cosmetic treatments in the area(s) to be treated: Skin tightening procedure within the past year; Injectable filler of any type within the past: i.12 months for Hyaluronic acid fillers (example Rstylane) ii.12 months for Ca Hydroxyapatite fillers (example Radiesse) iii. 24 months for Poly-L-Lactic acid fillers (example Sculptra) iv. Ever for permanent fillers (example Silicone, ArteFill) c. Neurotoxins within the past six months; d. Ablative resurfacing laser treatment; e. Nonablative, rejuvenative laser or light treatment within the past six months; f. Surgical dermabrasion or deep facial peels; g. Facelifts, blepharoplasty, or browlift within the past 18 months; or h. Any history of contour threads. History of using the following prescription medications: Accutane or other systemic retinoids within the past six months; Topical Retinoids within the past two weeks; Antiplatelet agents/Anticoagulants (Coumadin, Heparin, Plavix); Psychiatric drugs that in the investigators opinion would impair the participant from understanding the protocol requirements or understanding and signing the informed consent.
Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A - LT side simulines Ulthera treatment at EL2<br>Ulthera treatment using 'Ulthera System, prototype simulines transducers' on the LEFT side of the face and 'Ulthera System, standard transducers' on the RIGHT of the face at the default Energy Level [EL2]. | Device: Ulthera Treatment at EL2<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
| Active Comparator: Group B - RT side simulines Ulthera treatment at EL2<br>Ulthera treatment using 'Ulthera System, prototype simulines transducers' on the RIGHT side of the face and 'Ulthera System, standard transducers' on the LEFT side of the face at the default Energy Level [EL2] . | Device: Ulthera Treatment at EL2<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
| Active Comparator: Group C - LT side simulines Ulthera treatment at EL4<br>Ulthera treatment using 'Ulthera System, prototype simulines transducers' on the LEFT side of the face and 'Ulthera System, standard transducers' on the RIGHT of the face at a higher Energy Level [EL4]. | Device: Ulthera Treatment at EL4<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
| Active Comparator: Group D - RT side simulines Ulthera treatment at EL4<br>Ulthera treatment using 'Ulthera System, prototype simulines transducers' on the RIGHT side of the face and 'Ulthera System, standard transducers' on the LEFT side of the face at a higher Energy Level [EL4] . | Device: Ulthera Treatment at EL4<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
| Active Comparator: Group E - LT side simulines/standard Ulthera treatment at EL4<br>Ulthera treatment using a 4-4.5 'Ulthera System, prototype simulines transducers' and 7-3.0 'Ulthera System, standard transducers' on the LEFT side of the face and 'Ulthera System, standard transducers' on the RIGHT of the face at a higher Energy Level [EL4]. | Device: Ulthera Treatment at EL4<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
| Active Comparator: Group F - RT side simulines/standard Ulthera treatment at EL4<br>Ulthera treatment using a 4-4.5 'Ulthera System, prototype simulines transducers'and 7-3.0 standard transducer on the RIGHT side of the face and 'Ulthera System, standard transducers' on the LEFTof the face at a higher Energy Level [EL4]. | Device: Ulthera Treatment at EL4<br>* Focused ultrasound energy delivered below the surface of the skin.<br>* Other names: Ultherapy;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comfort level of standard transducers versus simulines transducers during Ultherapy® treatment | Subjects' treatment-related pain scores will be obtained using a validated 0-10 point Numeric Rating Scale while study treatment is being administered. It is estimated that each study treatment will be completed in approximately 90 minutes. | During study treatment. Participants will be followed for an average of 90 minutes. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brow lift obtained using simulines versus standard transducers | Brow lift as assessed by quantitative measurements of pre- to post-treatment photos. | 90 days post-treatment |
| Brow lift obtained using simulines versus standard transducers | Brow lift as assessed by quantitative measurements of pre- to post-treatment photos. | 180 days post-treatment |
| Improvement in overall lifting and tightening of skin | As assessed by a masked, qualitative assessment of photographs at 90 days post-treatment compared to baseline. | 90 days post-treatment |
| Improvement in overall lifting and tightening of skin | As assessed by a masked, qualitative assessment of photographs at 180 days post-treatment compared to baseline. | 180 days post-treatment |
| Patient Satisfaction | As assessed by a patient satisfaction questionnaire completed by the subject. | 90 days post-treatment |
| Efficiency of simulines versus standard transducers | As determined by comparing treatment times using the simulines transducers compared to treatment times using the standard transducers. | During study treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ulthera® System, Ultherapy®, Ulthera, Inc.
|
NCT01268475
|
Exercise Capacity in Bronchiectasis Resection
|
Bronchiectasis can be defined as an abnormal and irreversible dilatation of the bronchial tree due to repeated cycles of inflammation and infection, resulting in progressive loss of lung function. The surgical treatment by pulmonary resection or even lung transplantation is indicated in cases of bronchiectasis primary nonresponsive to appropriate medical treatment, or when associated with serious complications. There are few literature data on the influence of bronchiectasis in exercise capacity, quality of life and functional capacity, and the impact of lung resection in patients with this diagnosis. The primary objective of this study is to evaluate prospectively the impact of lung resection on exercise capacity in patients with clinical and radiological diagnosis of bronchiectasis. The secondary objective of this study is to evaluate the impact of lung resection on quality of life and lung function and to analyze the the presence of predictors of postoperative functional deterioration and the occurrence of complications.
|
Impact of Pulmonary Resection on Exercise Capacity in Patients With Bronchiectasis
|
Bronchiectasis
|
Inclusion Criteria:~Clinical and radiographic diagnosis of bronchiectasis;~Lack of adequate response to clinical treatment after 1 year of follow-up and / or presence of disease complications;~Agreement to participate of the study by signing of the Informed Consent Term~Exclusion Criteria:~Comorbidities that prevent the patient to undergo general anesthesia;~Musculoskeletal and/or psychomotor disability to perform pulmonary function tests and cardiopulmonary exercise tests;~Inability to understand the quality of life questionnaires;~Age over 90 years or less 18 years.
|
18 Years
|
90 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of Pulmonary Resection on Exercise Capacity | Exercise Capacity will be assessed using Cardiopulmonary Exercise Test. | Change from Baseline in Exercise Capacity at 3 months and Change from Baseline in Exercise Capacity at 9 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of Pulmonary Resection on Quality of Life. | Quality of life will be assessed using WHOQOL-Bref and SF-36 questionnaries. | Change from Baseline in Quality of Life at 3 months and Change from Baseline in Quality of Life at 9 months. |
| Impact of Pulmonary Resection on Lung Function. | Lung Function will be assessed using Spirometry Test. | Change from Baseline in Lung Function at 3 months and Change from Baseline in Lung Function at 9 months. |
|
Bronchiectasis, Quality of Life, Respiratory Function Tests, Exercise Test
|
Bronchiectasis, Bronchial Diseases, Respiratory Tract Diseases
|
Exercise Capacity in Bronchiectasis Resection
Study Overview
=================
Brief Summary
-----------------
Bronchiectasis can be defined as an abnormal and irreversible dilatation of the bronchial tree due to repeated cycles of inflammation and infection, resulting in progressive loss of lung function. The surgical treatment by pulmonary resection or even lung transplantation is indicated in cases of bronchiectasis primary nonresponsive to appropriate medical treatment, or when associated with serious complications. There are few literature data on the influence of bronchiectasis in exercise capacity, quality of life and functional capacity, and the impact of lung resection in patients with this diagnosis. The primary objective of this study is to evaluate prospectively the impact of lung resection on exercise capacity in patients with clinical and radiological diagnosis of bronchiectasis. The secondary objective of this study is to evaluate the impact of lung resection on quality of life and lung function and to analyze the the presence of predictors of postoperative functional deterioration and the occurrence of complications.
Official Title
-----------------
Impact of Pulmonary Resection on Exercise Capacity in Patients With Bronchiectasis
Conditions
-----------------
Bronchiectasis
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical and radiographic diagnosis of bronchiectasis; Lack of adequate response to clinical treatment after 1 year of follow-up and / or presence of disease complications; Agreement to participate of the study by signing of the Informed Consent Term Exclusion Criteria: Comorbidities that prevent the patient to undergo general anesthesia; Musculoskeletal and/or psychomotor disability to perform pulmonary function tests and cardiopulmonary exercise tests; Inability to understand the quality of life questionnaires; Age over 90 years or less 18 years.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of Pulmonary Resection on Exercise Capacity | Exercise Capacity will be assessed using Cardiopulmonary Exercise Test. | Change from Baseline in Exercise Capacity at 3 months and Change from Baseline in Exercise Capacity at 9 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of Pulmonary Resection on Quality of Life. | Quality of life will be assessed using WHOQOL-Bref and SF-36 questionnaries. | Change from Baseline in Quality of Life at 3 months and Change from Baseline in Quality of Life at 9 months. |
| Impact of Pulmonary Resection on Lung Function. | Lung Function will be assessed using Spirometry Test. | Change from Baseline in Lung Function at 3 months and Change from Baseline in Lung Function at 9 months. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bronchiectasis, Quality of Life, Respiratory Function Tests, Exercise Test
|
||||
NCT04848051
|
Implementing Fit Kit Colorectal Cancer (CRC) Screening in High Risk Populations
|
The purpose of this study is to understand best strategies for engaging high risk populations in a primary care setting to improved adherence to colorectal cancer screening guidelines. The results will be used to identify best practices that are scalable to other high-risk populations who are due or overdue for colorectal cancer (CRC) screening.
|
This is a prospective implementation science study that will test 4 different approaches to increase colorectal cancer screening in a local primary care setting that provides services to individuals who are under-resourced. The interventions will include reminders from primary care providers with and without additional information and/or services to help complete colorectal cancer screening. A review of electronic medical records will be used to identify baseline information assessing risk factors and personal and family CRC history. For arm 3 of the study, participants may elect to enroll in our existing health navigation program. If so, additional baseline information will be collected, including information on Social Determinants of Health (SDOH). For arm 4 of the study, a questionnaire will be used to assess knowledge about colorectal cancer screening. The questionnaire will be repeated after the intervention (informational video). For all arms of the study, the primary outcome (engagement on CRC screening, receipt of CRC screening, results of CRC screening) will be collected through EPIC.
|
Implementing Fit Kit Colorectal Cancer (CRC) Screening in High Risk Populations
|
Colorectal Cancer
|
* Behavioral: CRC screening reminder
* Behavioral: CRC Reminder & Short message
* Behavioral: CRC Reminder and Navigation Program
* Behavioral: CRC Reminder & CRC education
|
Inclusion Criteria:~be 50-74 years of old at the time of enrollment~have one valid medical encounter with CSHHC Columbus Ave. location or Dixwell location between the dates of 11/01/2019 and 11/30/2020~Exclusion Criteria:~• Documented history of colorectal cancer
|
50 Years
|
74 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of participants who completed their colorectal cancer screening | The total number of participants that completed their colorectal cancer screening will be measured between the different arms | 18 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to engagement | The time to engagement will be measured as the days between reminder or reminder + intervention and days to screening among the 4 arms | 18 months |
| Screening outcomes: results of screening | Screening outcomes will be defined as the following: descriptive summaries of the result of screening among the 4 arms. | 18 months |
| Screening outcomes: follow up | Screening outcomes will be defined as the following: descriptive summaries of need and completion of follow up among the 4 arms. | 18 months |
| Screening outcomes: biopsy results | Screening outcomes will be defined as the following: descriptive summaries of biopsy results (if needed) among the 4 arms. | 18 months |
| Screening outcomes: diagnostic results | Screening outcomes will be defined as the following: descriptive summaries of the diagnostic result(s) among the 4 arms. | 18 months |
|
Health Screening
|
Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRC screening reminder<br>Participants randomized to the CRC Reminder arm will receive reminder that they are due/overdue for CRC screening | Behavioral: CRC screening reminder<br>* Participants randomized to the CRC Reminder arm will receive reminder that they are due/overdue for CRC screening<br>|
| Experimental: CRC Reminder & Short message<br>Participants randomized to the CRC Reminder & short message arm will receive reminder that they are due/overdue for CRC screening and short message to encourage screening | Behavioral: CRC Reminder & Short message<br>* Participants randomized to the CRC Reminder & short message arm will receive reminder that they are due/overdue for CRC screening and short message to encourage screening<br>|
| Experimental: CRC Reminder and Navigation Program<br>Participants randomized to the CRC reminder and navigation program arm will receive reminder that they are due/overdue for CRC screening and short message to participate in the health navigation program that will connect participants to individually tailored resources and assistance | Behavioral: CRC Reminder and Navigation Program<br>* Participants randomized to the CRC reminder and navigation program arm will receive reminder that they are due/overdue for CRC screening and short message to participate in the health navigation program that will connect participants to individually tailored resources and assistance<br>|
| Experimental: CRC Reminder & CRC education<br>Participants randomized to the CRC reminder and CRC education program arm will receive reminder that they are due/overdue for CRC screening and offered short educational program conducted online | Behavioral: CRC Reminder & CRC education<br>* Participants randomized to the CRC reminder and CRC education program arm will receive reminder that they are due/overdue for CRC screening and offered short educational program conducted online<br>|
|
Implementing Fit Kit Colorectal Cancer (CRC) Screening in High Risk Populations
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to understand best strategies for engaging high risk populations in a primary care setting to improved adherence to colorectal cancer screening guidelines. The results will be used to identify best practices that are scalable to other high-risk populations who are due or overdue for colorectal cancer (CRC) screening.
Detailed Description
-----------------
This is a prospective implementation science study that will test 4 different approaches to increase colorectal cancer screening in a local primary care setting that provides services to individuals who are under-resourced. The interventions will include reminders from primary care providers with and without additional information and/or services to help complete colorectal cancer screening. A review of electronic medical records will be used to identify baseline information assessing risk factors and personal and family CRC history. For arm 3 of the study, participants may elect to enroll in our existing health navigation program. If so, additional baseline information will be collected, including information on Social Determinants of Health (SDOH). For arm 4 of the study, a questionnaire will be used to assess knowledge about colorectal cancer screening. The questionnaire will be repeated after the intervention (informational video). For all arms of the study, the primary outcome (engagement on CRC screening, receipt of CRC screening, results of CRC screening) will be collected through EPIC.
Official Title
-----------------
Implementing Fit Kit Colorectal Cancer (CRC) Screening in High Risk Populations
Conditions
-----------------
Colorectal Cancer
Intervention / Treatment
-----------------
* Behavioral: CRC screening reminder
* Behavioral: CRC Reminder & Short message
* Behavioral: CRC Reminder and Navigation Program
* Behavioral: CRC Reminder & CRC education
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: be 50-74 years of old at the time of enrollment have one valid medical encounter with CSHHC Columbus Ave. location or Dixwell location between the dates of 11/01/2019 and 11/30/2020 Exclusion Criteria: • Documented history of colorectal cancer
Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 74 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRC screening reminder<br>Participants randomized to the CRC Reminder arm will receive reminder that they are due/overdue for CRC screening | Behavioral: CRC screening reminder<br>* Participants randomized to the CRC Reminder arm will receive reminder that they are due/overdue for CRC screening<br>|
| Experimental: CRC Reminder & Short message<br>Participants randomized to the CRC Reminder & short message arm will receive reminder that they are due/overdue for CRC screening and short message to encourage screening | Behavioral: CRC Reminder & Short message<br>* Participants randomized to the CRC Reminder & short message arm will receive reminder that they are due/overdue for CRC screening and short message to encourage screening<br>|
| Experimental: CRC Reminder and Navigation Program<br>Participants randomized to the CRC reminder and navigation program arm will receive reminder that they are due/overdue for CRC screening and short message to participate in the health navigation program that will connect participants to individually tailored resources and assistance | Behavioral: CRC Reminder and Navigation Program<br>* Participants randomized to the CRC reminder and navigation program arm will receive reminder that they are due/overdue for CRC screening and short message to participate in the health navigation program that will connect participants to individually tailored resources and assistance<br>|
| Experimental: CRC Reminder & CRC education<br>Participants randomized to the CRC reminder and CRC education program arm will receive reminder that they are due/overdue for CRC screening and offered short educational program conducted online | Behavioral: CRC Reminder & CRC education<br>* Participants randomized to the CRC reminder and CRC education program arm will receive reminder that they are due/overdue for CRC screening and offered short educational program conducted online<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of participants who completed their colorectal cancer screening | The total number of participants that completed their colorectal cancer screening will be measured between the different arms | 18 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to engagement | The time to engagement will be measured as the days between reminder or reminder + intervention and days to screening among the 4 arms | 18 months |
| Screening outcomes: results of screening | Screening outcomes will be defined as the following: descriptive summaries of the result of screening among the 4 arms. | 18 months |
| Screening outcomes: follow up | Screening outcomes will be defined as the following: descriptive summaries of need and completion of follow up among the 4 arms. | 18 months |
| Screening outcomes: biopsy results | Screening outcomes will be defined as the following: descriptive summaries of biopsy results (if needed) among the 4 arms. | 18 months |
| Screening outcomes: diagnostic results | Screening outcomes will be defined as the following: descriptive summaries of the diagnostic result(s) among the 4 arms. | 18 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Health Screening
|
NCT04387149
|
Biomarkers of Acute Kidney Injury Following Cardiac Surgery
|
Acute kidney injury occurs in up to 30% of patients undergoing cardiac surgery. Cardiac surgery associated-acute kidney injury (CSA-AKI) is characterized by a sudden and sustained decrease in renal function with insufficient elimination waste products. The problem is that postoperative diagnosis of CSA-AKI is delayed because it relies solely upon the slow and unreliable rise in serum creatinine (SCr) levels that may lead to delayed start in treatment and increased risk of adverse outcomes. We hypothesize that Matrix Metalloproteins (MMPs) -2, -9 and Neutrophil gelatinase-associated lipocalin (NGAL) are associated with and earlier detectors of CSA-AKI compared to levels of SCr.
|
Cardiopulmonary bypass (CPB), although essential to the performance of most cardiac operations, has been shown to cause injury to other organs, particularly to the kidneys and brain. Matrix Metalloproteins (MMPs) are ubiquitous proteolytic enzymes that degrade extracellular matrix and have been shown to be involved in injury to transplant kidneys. To date, no interventions are available to decrease the risk of cardiac surgery associated-acute kidney injury (CSA-AKI).~NGAL is a known indicator of injury to kidney, thus making it a promising biomarker for CSA-AKI. It may be that a single biomarker will not be sensitive and specific across the spectrum of CSA-AKI. This research investigates MMP-2, -9 and Neutrophil gelatinase-associated lipocalin (NGAL) and their association with and earlier detection of CSA-AKI compared to levels of SCr.~We hypothesize that increased activity of MMPs are associated with CSA-AKI. Furthermore, MMP-2 and/ or -9 may be predictors and/ or biomarkers for the early detection of CSA-AKI compared to serum levels of creatinine.
|
Biomarkers of Acute Kidney Injury Following Cardiopulmonary Bypass Surgery-supported Cardiac Surgery
|
Novel Biomarkers of Acute Kidney Injury Following Cardiac Surgery
|
Inclusion Criteria:~The inclusion criteria consisted of both sexes, 18-85 years of age, undergoing elective or urgent cardiac surgery with a hemoglobin (Hgb) >100 g/L.~Exclusion Criteria:~The exclusion criteria included were patients for emergent surgery, pre-existing chronic kidney disease (eGFR<30 mL/min) on dialysis or prescribed nephrotoxic mediations.
|
18 Years
|
85 Years
|
All
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increased MMP-2 and -9 in patients that develop CSA-AKI | Increased MMP-2 and -9 activity in serum and or urine in patients that develop CSA-AKI | Pre-CPB, 10 min post-CPB time point, 4 hours post-CPD |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increased NGAL levels in patients that develop CSA-AKI | Increased NGAL levels in serum and or urine in patients that develop CSA-AKI | Pre-CPB, 10 min post-CPB time point, 4 hours post-CPD |
|
Acute Kidney Injury, Wounds and Injuries, Renal Insufficiency, Kidney Diseases, Urologic Diseases, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Male Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CSA-AKI<br>Patients that developed cardiac surgery-associated Acute Kidney Injury | |
| non CSA-AKI<br>Patients that did not developed cardiac surgery-associated Acute Kidney Injury | |
|
Biomarkers of Acute Kidney Injury Following Cardiac Surgery
Study Overview
=================
Brief Summary
-----------------
Acute kidney injury occurs in up to 30% of patients undergoing cardiac surgery. Cardiac surgery associated-acute kidney injury (CSA-AKI) is characterized by a sudden and sustained decrease in renal function with insufficient elimination waste products. The problem is that postoperative diagnosis of CSA-AKI is delayed because it relies solely upon the slow and unreliable rise in serum creatinine (SCr) levels that may lead to delayed start in treatment and increased risk of adverse outcomes. We hypothesize that Matrix Metalloproteins (MMPs) -2, -9 and Neutrophil gelatinase-associated lipocalin (NGAL) are associated with and earlier detectors of CSA-AKI compared to levels of SCr.
Detailed Description
-----------------
Cardiopulmonary bypass (CPB), although essential to the performance of most cardiac operations, has been shown to cause injury to other organs, particularly to the kidneys and brain. Matrix Metalloproteins (MMPs) are ubiquitous proteolytic enzymes that degrade extracellular matrix and have been shown to be involved in injury to transplant kidneys. To date, no interventions are available to decrease the risk of cardiac surgery associated-acute kidney injury (CSA-AKI). NGAL is a known indicator of injury to kidney, thus making it a promising biomarker for CSA-AKI. It may be that a single biomarker will not be sensitive and specific across the spectrum of CSA-AKI. This research investigates MMP-2, -9 and Neutrophil gelatinase-associated lipocalin (NGAL) and their association with and earlier detection of CSA-AKI compared to levels of SCr. We hypothesize that increased activity of MMPs are associated with CSA-AKI. Furthermore, MMP-2 and/ or -9 may be predictors and/ or biomarkers for the early detection of CSA-AKI compared to serum levels of creatinine.
Official Title
-----------------
Biomarkers of Acute Kidney Injury Following Cardiopulmonary Bypass Surgery-supported Cardiac Surgery
Conditions
-----------------
Novel Biomarkers of Acute Kidney Injury Following Cardiac Surgery
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The inclusion criteria consisted of both sexes, 18-85 years of age, undergoing elective or urgent cardiac surgery with a hemoglobin (Hgb) >100 g/L. Exclusion Criteria: The exclusion criteria included were patients for emergent surgery, pre-existing chronic kidney disease (eGFR<30 mL/min) on dialysis or prescribed nephrotoxic mediations.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years
Sexes Eligible for Study
-----------------
All
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CSA-AKI<br>Patients that developed cardiac surgery-associated Acute Kidney Injury | |
| non CSA-AKI<br>Patients that did not developed cardiac surgery-associated Acute Kidney Injury | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increased MMP-2 and -9 in patients that develop CSA-AKI | Increased MMP-2 and -9 activity in serum and or urine in patients that develop CSA-AKI | Pre-CPB, 10 min post-CPB time point, 4 hours post-CPD |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increased NGAL levels in patients that develop CSA-AKI | Increased NGAL levels in serum and or urine in patients that develop CSA-AKI | Pre-CPB, 10 min post-CPB time point, 4 hours post-CPD |
|
|||
NCT02459041
|
Clinical Impact of EUS Elastography Mean Strain Histograms (SH) and Contrast Peak-enhancement in Focal Pancreatic Masses and Lymph Nodes
|
The study protocol is based on a multi-center semi-quantitative approach of EUS elastography data in combination with contrast-enhanced EUS, consisting of measuring SR and SH for focal pancreatic masses and lymph nodes, as well as several parameters of CE-EUS based on time-intensity-curve (TIC) analysis. A number of parameters must be taken into consideration, as the ROIs are still manually selected by the user. The aim of the study is to establish an EUS based diagnostic algorithm in patients with pancreatic masses and lymph nodes, with negative or inconclusive cytopathology after EUS-FNA, based on previously published results and cut-offs of elastography and contrast-enhancement. The proposed algorithm of sequential use of real-time elastography, followed by contrast-enhanced EUS could be a good clinical tool to help select the patients with possible pancreatic adenocarcinoma or malignant lymph nodes, in the setting of patients with negative EUS-FNA results.
|
1. Background Endoscopic ultrasound (EUS) is a technique with a major clinical impact in digestive diseases, determining a change in the diagnosis and management of more than half of examined patients [1]. Recent advances in EUS-FNA techniques, but also the development of real-time EUS elastography and contrast-enhancement, allowed a better characterization of focal pancreatic masses, with possible implications in the management of patients with negative EUS-FNA and a strong suspicion of malignancy.~1.a Elastography Elastography is a recent ultrasound method used for the reconstruction of tissue elasticity distribution in real-time [2]. The method allows the calculation of the elasticity modulus, consequently showing differences in tissue hardness patterns that are determined by diseases. The main intended use is to differentiate between benign and malignant focal lesions based on the significantly smaller strain of the latter [3]. Second generation elastography introduces strain ratio (SR) and strain histogram (SH) as reproducible parametric measurements that retrieve numerical values in real time, adding quantification possibilities to the technique [4]. Elastography typically estimates the axial strain (along the direction of insonification / compression) by analyzing ultrasonic signals obtained with standard ultrasonographic systems - the RF signals returned from tissue structures before and after slight compression (about 1%) are compared [5]. Tissue elastography can be easily performed with conventional probes, including the linear EUS probes used for the examination of the pancreas and/or lymph nodes. The calculation of tissue elasticity distribution is performed in real-time under freehand compression and the examination results are represented as transparent overlay colour images overimposed on the conventional gray-scale B-mode images [6]. Thus, this method allows the characterization of many tumors, because they are stiffer than normal tissues. Ultrasound elastography was previously used for the diagnosis of non-digestive as well as digestive tumors: breast lesions [7], prostate cancer [8], thyroid nodules [9], rectal tumors [10]. Regarding the diagnosis of pancreatic focal masses, some authors could not differentiate between malignancy and benign tumors or chronic pancreatitis [11], while others have obtained good results, especially when using computer assisted means of evaluation like hue histogram analysis [12] and artificial neural networks [13]. More recently, lymph node involvement of several tumors has been succesfully determined using this method: esophagus [14], oral squamous cell carcinoma [15], breast cancer [16].~Since elastography images and movies represent a qualitative type output that entails a subjective interpretation by the examiner, human bias is always susceptible to interfere with the results and diagnoses, due to color perception errors, moving artifacts, or possible selection bias induced by the analysis of still images. More objective, computer-assisted semi-quantitative means of interpreting the results were developed, but these have the disadvantage of being labor-intensive and using third-party software that cannot be used in real time [17]. Second generation elastography introduces strain ratio (SR) and strain histogram (SH) as two reproducible measurements that retrieve numerical values in real time, thus greatly reducing the human bias without the need for third-party software [4]. SR calculates the relative strain between two regions of interest (ROI) (normal and pathological). SH measures the strain values of elemental areas inside a ROI and divides the measurement range into intervals; if the strain value of an element falls into an interval, its initial area normalized by the initial total surface area is added to the running total of that interval; the total values of each interval are used to produce a graph and an average value. Both SR and SH have already been used in vivo for pancreatic masses or lymph nodes, with promising results [18].~b Contrast-enhancement Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use for diagnostic imaging [19]. The study of the pancreas is a new and promising application of contrast-enhanced ultrasound (CE-US), including contrast-enhanced endoscopic ultrasound (CE-EUS). The technique is not indicated to improve the detection of pancreatic lesions, but to improve the delineation and differential diagnosis of pancreatic lesions [20-23]. One of the fluoro-gas-containing contrast agents used in CE-US and CE-EUS is Sonovue®, which consists of phospholipids-stabilized bubbles of sulfurhexafluoride (SF6) [24]. Sonovue® is isotonic, stable and resistant to pressure, with a viscosity similar to blood. It does not diffuse into the extravascular compartment remaining within the blood vessels until the gas dissolves and is eliminated in the expired air (blood pool contrast agent) [25]. The safety profile of SonoVue showed a very low incidence of side effects; it is not nephrotoxic and the incidence of severe hypersensitivity is similar to other magnetic resonance imaging contrast agents. Moreover, Sono-Vue is approved for clinical use in EU countries. The blood supply of the pancreas is entirely arterial, making contrast-enhanced examinations feasible and readily available. Based on the European Federation Societies of Ultrasound in Medicine and Biology guidelines and recommendations, updated in 2008, two phases were defined for CE-US and CE-EUS of the pancreas: an early/arterial phase (starting from 10 to 30 seconds) and a venous/late phase (from 30 to 120 seconds) [19].~Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques [22-27]. The specificity of the discrimination between benign and malignant focal pancreatic lesions was found to be 93.3% using power Doppler contrast-enhanced EUS (PD-CE-EUS) compared with 83.3% for conventional EUS [26]. The hypovascular aspect of lesions under PD-CE-EUS seemed highly sensitive and specific (higher than 90%) for adenocarcinoma in several published studies [22-27]. During PD-CE-EUS examinations the ultrasound frequency returned to the transducer is the same with that transmitted, but the method is associated with artifacts resulting from turbulent flow (flash and overpainting) [28]. At CE-EUS, ductal adenocarcinoma is typically hypoenhanced compared to the adjacent pancreatic tissue in all phases [19]. Furthermore, the lesion size and margins are better visualized, as well as the relationship with peripancreatic arteries and veins. Focal lesions in chronic pancreatitis are reported to have similar or hyper enhancement features as compared to the normal pancreatic parenchyma [19].~Dedicated contrast-enhanced harmonic EUS techniques (based on a low mechanical index) are recently available in new EUS systems. The harmonic frequencies returned during CEH-EUS are different from those transmitted by the transducer and are the result of non-linear oscillations of the microbubbles [24]. The image obtained is an addition of the signal created by the distortion of the microbubbles and the tissue-derived signal. This can be optimized by using low MI, which allows minimum bubble destruction and complete subtraction of the tissue derived signal, obtaining a high resolution continuous real-time assessment of the microvascularization during the contrast uptake period (real-time perfusion imaging) [29-31]. CEH-EUS allows a more precise location of vascular structures within the parenchyma and focal abnormalities, with better delineation of pancreatic lesions than EUS, especially in the cases where air or fat causes artifacts and insufficient visualization of the pancreatic parenchyma. An initial pilot study described an experimental technique of CEH-EUS based on a linear prototype EUS scope, a low mechanical index (0.08 - 0.25) and a 2nd generation contrast agent (Sono-Vue), which allowed the visualization of early arterial phase and late parenchymal phase enhancement of the pancreas [32]. Another pilot study demonstrated both real-time continuous images of finely branching vessels of the pancreas and intermittent homogenous parenchymal perfusion images, by using a radial prototype EUS scope, a low mechanical index (0.4) and a 2nd generation contrast agent (Sono-Vue) [33]. Several other research groups already reported the feasibility of CEH-EUS with low mechanical index [34-36]. The sensitivity, specificity and accuracy for diagnosing pancreatic adenocarcinoma were 88%, 89%, and 88.5% in one study [34] and 80%, 91.7%, and 86% in the other study [33]. However, the data is still limited and a prospective, multicentric blinded study would certainly be necessary.~The study protocol is based on a multi-center semi-quantitative approach of EUS elastography data in combination with contrast-enhanced EUS, consisting of measuring SR and SH for focal pancreatic masses and lymph nodes, as well as several parameters of CE-EUS based on time-intensity-curve (TIC) analysis. A number of parameters must be taken into consideration, as the ROIs are still manually selected by the user. The aim of the study is to establish an EUS based diagnostic algorithm in patients with pancreatic masses and lymph nodes, with negative or inconclusive cytopathology after EUS-FNA, based on previously published results and cut-offs of elastography and contrast-enhancement. The proposed algorithm of sequential use of real-time elastography, followed by contrast-enhanced EUS could be a good clinical tool to help select the patients with possible pancreatic adenocarcinoma or malignant lymph nodes, in the setting of patients with negative EUS-FNA results.~Aims of the study The aim of the study is to assess quantitative elastography and contrast-enhancement parameters during EUS examinations of focal pancreatic masses and lymph nodes, to standardize an algorithm for their use and to consequently differentiate benign vs malignant pancreatic masses and evaluate lymph node involvement in a prospective multicenter design.~Patients and methods The study design is prospective, blinded and multi-center, comparing endoscopic ultrasound elastography (EG-EUS) and contrast-enhnecement (CE-EUS) results for the characterization of focal pancreatic masses and lymph nodes by using parametric measurements, in comparison with the gold standard represented by pathology.~The study will be performed with the approval of the institutional board (ethical committee) review of each center. The complete study protocol and particpating centers will be uploaded on ClinicalTrials.gov, the registry of federally and privately supported clinical trials conducted in the United States and around the world.~Inclusion criteria~Patients diagnosed with solid pancreatic tumor masses, with cytological / histo-logical confirmation~Patients with or without suspected lymph node involvement are eligible~Age 18 to 90 years old, men or women~Signed informed consent for EG-EUS, CE-EUS and FNA biopsy Exclusion criteria~Prior surgical treatment with curative intent or chemo-radiotherapy~Patients diagnosed with mucin producing tumors, pancreatic cystic tumors, etc.~Data collection~• Personal data (name, surname, age, admission date, SSN, diagnosis at admission)~Imaging tests~All patients with a suspicion of pancreatic masses or lymph nodes should undergo EUS, with sequential EG-EUS and CE-EUS~EUS with EUS-guided FNA and elastography~Protocol of EUS with EUS-FNA should include linear EUS instruments with complete examinations of the pancreas.~Tumor characteristics (echogenicity, echostructure, size) will be described as well as presence / absence of power Doppler signals.~EUS-FNA will be performed in all pancreatic masses with at least three passes~All examiners should be blinded for the results of pathology~EG-EUS procedure:~EUS-EG will be performed during usual EUS examinations, with two movies of 10 seconds recorded on the embedded HDD in order to minimize variability and to increase repeatability of acquisition.~A two panel image with the usual conventional gray-scale B-mode EUS image on the right side and with the elastography image on the left side will be used. The same parameters will be set-up in all systems used: e-dynamic range 2, persistence 3, etc.~The region of interest for EUS-EG will be preferably larger than the focal mass (approximately 50%-50%), in order to include the surrounding structures. If the focal mass is larger than 3 cm, part of the mass will be included in the ROI, as well as the surrounding structures (preferably avoiding large vessels). Very large ROI for the elastography calculations will be avoided due to the appearance of side artifacts.~The following pre-settings will be used in all centers: elastography colour map 1, frame rejection 2, noise rejection 2, persistence 3, dynamic rage 4, smoothing 2, blend 50%.~SR and SH will be measured; with three measurements made and recorded on the embedded HDD. For SR, the reference area should be placed at the same level with the lesion, if possible.~CE-EUS procedure:~A two panel image with the usual conventional gray-scale B-mode EUS image on the right side and with the contrast harmonic image on the left side will be used, according to pre-established presets.~The starting point of the timer will be considered the moment of intravenous contrast injection (Sonovue 4.8 mL).~CE-EUS will be performed during usual EUS examinations, with the whole movie (T0-T120s) recorded on the embedded HDD of the ultrasound system, for later analysis.~A low mechanical index procedure (dynamic wide-band contrast harmo¬nic imaging mode) will be used, with a mechanical index of 0.2 and corresponding powers.~The following pre-settings will be used in all centers: contrast mode dCHI-W, WPI-R/P (resolution / penetration for superficial vs deep structures), mechanical index (variable starting with 0.1, preferred 0.2), MI gray-scale (0.03), grey map 4, AGC 0, R-filter C, persistence 2, dynamic range 50, B-colour 21, smoothing 3, gamma curve linear.~In order to minimize human bias, all post-processing and computer analysis of digital movies will be performed within the coordinating IT Center, with all programmers and statisticians being blinded to the clinical, imaging and pathological data.~Off-line analysis of time-intensity curves will be performed using Vue-Box, which yields the following quantitative parameters: Peak Enhancement (PE), Wash-in Area Under the Curve (Wi-AUC), Rise Time (RT), mean Transit Time (mTT), Time To Peak (TTP), Wash-in Rate (WiR) and Wash-in Perfusion Index (WiPI). The software also provides referenced values (expressed in percentages), aligning the set of values for the tumor ROI to the parenchymal ones.~Final diagnosis~A positive cytological diagnosis will be taken as a final proof of malignancy of the pancreas mass or lymph node. The diagnoses obtained by EUS-FNA will be further verified either by surgery or during a clinical follow-up of at least 6 months.~The diagnosis of chronic pancreatitis will be based on the clinical information (history of alcohol abuse, previous diagnosis of chronic pancreatitis or diabetes mellitus), as well as a combination of imaging methods (ultrasound, CT and EUS). At least four criteria of chronic pancreatitis during EUS will be considered for the positive diagnosis. The diagnosis of chronic pseudotumoral pancreatitis or benign lymph nodes will always be confirmed by surgery or by a follow-up of at least six months used to exclude malignancy in the patients that will not be operated on.~Pathology samples obtained from duodeno-pancreatectomies or caudal pancreatecto-mies done with curative intent, as well as microhistological fragments obtained through EUS-FNA biopsy will be processed by paraffin embedding with usual stainings (haematoxylin-eosin), with subsequent immune-histochemistry at the discretion of the participating centers pathologists in order to exclude neuroendocrine tumors / pancreatic metastases.~The patients will be followed-up for at least six months through clinical examination, biological exams and transabdominal ultrasound, eventually with a repeat spiral CT / EUS after six months.~Statistical analysis~Descriptive statistics~All results will be expressed as mean ± standard deviation (SD). Differences between the patients with pancreatic cancer and chronic pancreatitis will performed by the two-sample t-test (two independent samples). Since this parametric method makes assumptions about normality and similar variances, we will initially perform both the Kolmogorov-Smirnov and Shapiro-Wilk W normality tests and verify the equality of variances assumption with the F test. In the case of the two-sample t-test, we will also perform the non-parametric alternative given by the Mann-Whitney U test, since in some instances it may even offer greater power to reject the null hypothesis than the t-test.~Since with more than two groups of observations it is far better to use a single analysis that enables us to look at all the data in the same time, we will also perform the one-way analysis of variance (ANOVA) method with the same baseline assumptions. A p-value less than 0.05 will be considered as statistically significant.~Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EG-EUS and CE-EUS will be determined in comparison with the final diagnosis. Also, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for the subgroup of patients with negative EUS-FNA and a positive diagnosisi of malignancy during ensuing follow-up will be calculated separately.~Power analysis~The estimated number of patients included is at least 210, based on at least 10 centers with at least 20 patients each, which will be enrolled in a 12 months period. The power analysis was based on the following assumption: in order to use the powerful t-test for independent samples, a sample size equaling 105 patients in each group is sufficient to provide 95% statistical power to detect a difference of 5% in mean, for a type I error alpha = 0.05, and the population standard deviation = 10%.~The difference in mean was based on previously published data which report an accuracy of approximately 80-85% for EUS-FNA, and 90% for EG-EUS and/or CE-EUS.
|
Real-time Semi-quantification of Endoscopic Ultrasound Elastography and Contrast-enhancement Using Strain Histograms (SH) and Contrast-enhancement (CE) for the Differentiation of Focal Pancreatic Masses and the Assessment of Lymph Node Involvement
|
Pancreatic Cancer, Secondary Malignant Neoplasm of Lymph Node, Benign Neoplasm of Lymph Nodes, Benign Pancreatic Tumors
|
* Other: Elastography, contrast enhancement
|
Inclusion Criteria:~Patients diagnosed with solid pancreatic tumor masses, with cytological / histo-logical confirmation~Patients with or without suspected lymph node involvement are eligible~Age 18 to 90 years old, men or women~Signed informed consent for EG-EUS, CE-EUS and FNA biopsy~Exclusion Criteria:~Prior surgical treatment with curative intent or chemo-radiotherapy~Patients diagnosed with mucin producing tumors, pancreatic cystic tumors, etc.
|
18 Years
|
90 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Strain histogram and contrast enhancement during EUS in pancreatic masses and lymph nodes | | 12 months |
|
Neoplasms, Pancreatic Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Endocrine Gland Neoplasms, Digestive System Diseases, Pancreatic Diseases, Endocrine System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pancreatic cancer<br>Consecutively admitted patients with pancreatic cancer confirmed by EUS-guided FNA.~EG-EUS and CE-EUS will be applied in all patients. | Other: Elastography, contrast enhancement<br>* Elastography is an ultrasound method used for the reconstruction of tissue elasticity distribution in real-time. The main intended use is to differentiate between benign and malignant focal lesions based on the significantly smaller strain of the latter real time. Tissue elastography can be easily performed with conventional probes, including the linear EUS probes used for the examination of the pancreas and/or lymph nodes.~Contrast-enhancement Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use for diagnostic imaging. Pancreatic adenocarcinomas are usually hypovascular tumors.<br>|
| Benign pancreatic masses<br>Consecutively admitted patients with benign pancreatic masses with negative EUS-guided FNA.~EG-EUS and CE-EUS will be applied in all patients. | Other: Elastography, contrast enhancement<br>* Elastography is an ultrasound method used for the reconstruction of tissue elasticity distribution in real-time. The main intended use is to differentiate between benign and malignant focal lesions based on the significantly smaller strain of the latter real time. Tissue elastography can be easily performed with conventional probes, including the linear EUS probes used for the examination of the pancreas and/or lymph nodes.~Contrast-enhancement Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use for diagnostic imaging. Pancreatic adenocarcinomas are usually hypovascular tumors.<br>|
| Malignant lymph nodes<br>Consecutively admitted patients with malignant lymphnodes confirmed by EUS-guided FNA.~EG-EUS will be applied in all patients. | Other: Elastography, contrast enhancement<br>* Elastography is an ultrasound method used for the reconstruction of tissue elasticity distribution in real-time. The main intended use is to differentiate between benign and malignant focal lesions based on the significantly smaller strain of the latter real time. Tissue elastography can be easily performed with conventional probes, including the linear EUS probes used for the examination of the pancreas and/or lymph nodes.~Contrast-enhancement Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use for diagnostic imaging. Pancreatic adenocarcinomas are usually hypovascular tumors.<br>|
| Benign lymph nodes<br>Consecutively admitted patients with benign lymphnodes with negative EUS-guided FNA.~EG-EUS will be applied in all patients. | Other: Elastography, contrast enhancement<br>* Elastography is an ultrasound method used for the reconstruction of tissue elasticity distribution in real-time. The main intended use is to differentiate between benign and malignant focal lesions based on the significantly smaller strain of the latter real time. Tissue elastography can be easily performed with conventional probes, including the linear EUS probes used for the examination of the pancreas and/or lymph nodes.~Contrast-enhancement Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use for diagnostic imaging. Pancreatic adenocarcinomas are usually hypovascular tumors.<br>|
|
Clinical Impact of EUS Elastography Mean Strain Histograms (SH) and Contrast Peak-enhancement in Focal Pancreatic Masses and Lymph Nodes
Study Overview
=================
Brief Summary
-----------------
The study protocol is based on a multi-center semi-quantitative approach of EUS elastography data in combination with contrast-enhanced EUS, consisting of measuring SR and SH for focal pancreatic masses and lymph nodes, as well as several parameters of CE-EUS based on time-intensity-curve (TIC) analysis. A number of parameters must be taken into consideration, as the ROIs are still manually selected by the user. The aim of the study is to establish an EUS based diagnostic algorithm in patients with pancreatic masses and lymph nodes, with negative or inconclusive cytopathology after EUS-FNA, based on previously published results and cut-offs of elastography and contrast-enhancement. The proposed algorithm of sequential use of real-time elastography, followed by contrast-enhanced EUS could be a good clinical tool to help select the patients with possible pancreatic adenocarcinoma or malignant lymph nodes, in the setting of patients with negative EUS-FNA results.
Detailed Description
-----------------
1. Background Endoscopic ultrasound (EUS) is a technique with a major clinical impact in digestive diseases, determining a change in the diagnosis and management of more than half of examined patients [1]. Recent advances in EUS-FNA techniques, but also the development of real-time EUS elastography and contrast-enhancement, allowed a better characterization of focal pancreatic masses, with possible implications in the management of patients with negative EUS-FNA and a strong suspicion of malignancy. 1.a Elastography Elastography is a recent ultrasound method used for the reconstruction of tissue elasticity distribution in real-time [2]. The method allows the calculation of the elasticity modulus, consequently showing differences in tissue hardness patterns that are determined by diseases. The main intended use is to differentiate between benign and malignant focal lesions based on the significantly smaller strain of the latter [3]. Second generation elastography introduces strain ratio (SR) and strain histogram (SH) as reproducible parametric measurements that retrieve numerical values in real time, adding quantification possibilities to the technique [4]. Elastography typically estimates the axial strain (along the direction of insonification / compression) by analyzing ultrasonic signals obtained with standard ultrasonographic systems - the RF signals returned from tissue structures before and after slight compression (about 1%) are compared [5]. Tissue elastography can be easily performed with conventional probes, including the linear EUS probes used for the examination of the pancreas and/or lymph nodes. The calculation of tissue elasticity distribution is performed in real-time under freehand compression and the examination results are represented as transparent overlay colour images overimposed on the conventional gray-scale B-mode images [6]. Thus, this method allows the characterization of many tumors, because they are stiffer than normal tissues. Ultrasound elastography was previously used for the diagnosis of non-digestive as well as digestive tumors: breast lesions [7], prostate cancer [8], thyroid nodules [9], rectal tumors [10]. Regarding the diagnosis of pancreatic focal masses, some authors could not differentiate between malignancy and benign tumors or chronic pancreatitis [11], while others have obtained good results, especially when using computer assisted means of evaluation like hue histogram analysis [12] and artificial neural networks [13]. More recently, lymph node involvement of several tumors has been succesfully determined using this method: esophagus [14], oral squamous cell carcinoma [15], breast cancer [16]. Since elastography images and movies represent a qualitative type output that entails a subjective interpretation by the examiner, human bias is always susceptible to interfere with the results and diagnoses, due to color perception errors, moving artifacts, or possible selection bias induced by the analysis of still images. More objective, computer-assisted semi-quantitative means of interpreting the results were developed, but these have the disadvantage of being labor-intensive and using third-party software that cannot be used in real time [17]. Second generation elastography introduces strain ratio (SR) and strain histogram (SH) as two reproducible measurements that retrieve numerical values in real time, thus greatly reducing the human bias without the need for third-party software [4]. SR calculates the relative strain between two regions of interest (ROI) (normal and pathological). SH measures the strain values of elemental areas inside a ROI and divides the measurement range into intervals; if the strain value of an element falls into an interval, its initial area normalized by the initial total surface area is added to the running total of that interval; the total values of each interval are used to produce a graph and an average value. Both SR and SH have already been used in vivo for pancreatic masses or lymph nodes, with promising results [18]. b Contrast-enhancement Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use for diagnostic imaging [19]. The study of the pancreas is a new and promising application of contrast-enhanced ultrasound (CE-US), including contrast-enhanced endoscopic ultrasound (CE-EUS). The technique is not indicated to improve the detection of pancreatic lesions, but to improve the delineation and differential diagnosis of pancreatic lesions [20-23]. One of the fluoro-gas-containing contrast agents used in CE-US and CE-EUS is Sonovue®, which consists of phospholipids-stabilized bubbles of sulfurhexafluoride (SF6) [24]. Sonovue® is isotonic, stable and resistant to pressure, with a viscosity similar to blood. It does not diffuse into the extravascular compartment remaining within the blood vessels until the gas dissolves and is eliminated in the expired air (blood pool contrast agent) [25]. The safety profile of SonoVue showed a very low incidence of side effects; it is not nephrotoxic and the incidence of severe hypersensitivity is similar to other magnetic resonance imaging contrast agents. Moreover, Sono-Vue is approved for clinical use in EU countries. The blood supply of the pancreas is entirely arterial, making contrast-enhanced examinations feasible and readily available. Based on the European Federation Societies of Ultrasound in Medicine and Biology guidelines and recommendations, updated in 2008, two phases were defined for CE-US and CE-EUS of the pancreas: an early/arterial phase (starting from 10 to 30 seconds) and a venous/late phase (from 30 to 120 seconds) [19]. Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques [22-27]. The specificity of the discrimination between benign and malignant focal pancreatic lesions was found to be 93.3% using power Doppler contrast-enhanced EUS (PD-CE-EUS) compared with 83.3% for conventional EUS [26]. The hypovascular aspect of lesions under PD-CE-EUS seemed highly sensitive and specific (higher than 90%) for adenocarcinoma in several published studies [22-27]. During PD-CE-EUS examinations the ultrasound frequency returned to the transducer is the same with that transmitted, but the method is associated with artifacts resulting from turbulent flow (flash and overpainting) [28]. At CE-EUS, ductal adenocarcinoma is typically hypoenhanced compared to the adjacent pancreatic tissue in all phases [19]. Furthermore, the lesion size and margins are better visualized, as well as the relationship with peripancreatic arteries and veins. Focal lesions in chronic pancreatitis are reported to have similar or hyper enhancement features as compared to the normal pancreatic parenchyma [19]. Dedicated contrast-enhanced harmonic EUS techniques (based on a low mechanical index) are recently available in new EUS systems. The harmonic frequencies returned during CEH-EUS are different from those transmitted by the transducer and are the result of non-linear oscillations of the microbubbles [24]. The image obtained is an addition of the signal created by the distortion of the microbubbles and the tissue-derived signal. This can be optimized by using low MI, which allows minimum bubble destruction and complete subtraction of the tissue derived signal, obtaining a high resolution continuous real-time assessment of the microvascularization during the contrast uptake period (real-time perfusion imaging) [29-31]. CEH-EUS allows a more precise location of vascular structures within the parenchyma and focal abnormalities, with better delineation of pancreatic lesions than EUS, especially in the cases where air or fat causes artifacts and insufficient visualization of the pancreatic parenchyma. An initial pilot study described an experimental technique of CEH-EUS based on a linear prototype EUS scope, a low mechanical index (0.08 - 0.25) and a 2nd generation contrast agent (Sono-Vue), which allowed the visualization of early arterial phase and late parenchymal phase enhancement of the pancreas [32]. Another pilot study demonstrated both real-time continuous images of finely branching vessels of the pancreas and intermittent homogenous parenchymal perfusion images, by using a radial prototype EUS scope, a low mechanical index (0.4) and a 2nd generation contrast agent (Sono-Vue) [33]. Several other research groups already reported the feasibility of CEH-EUS with low mechanical index [34-36]. The sensitivity, specificity and accuracy for diagnosing pancreatic adenocarcinoma were 88%, 89%, and 88.5% in one study [34] and 80%, 91.7%, and 86% in the other study [33]. However, the data is still limited and a prospective, multicentric blinded study would certainly be necessary. The study protocol is based on a multi-center semi-quantitative approach of EUS elastography data in combination with contrast-enhanced EUS, consisting of measuring SR and SH for focal pancreatic masses and lymph nodes, as well as several parameters of CE-EUS based on time-intensity-curve (TIC) analysis. A number of parameters must be taken into consideration, as the ROIs are still manually selected by the user. The aim of the study is to establish an EUS based diagnostic algorithm in patients with pancreatic masses and lymph nodes, with negative or inconclusive cytopathology after EUS-FNA, based on previously published results and cut-offs of elastography and contrast-enhancement. The proposed algorithm of sequential use of real-time elastography, followed by contrast-enhanced EUS could be a good clinical tool to help select the patients with possible pancreatic adenocarcinoma or malignant lymph nodes, in the setting of patients with negative EUS-FNA results. Aims of the study The aim of the study is to assess quantitative elastography and contrast-enhancement parameters during EUS examinations of focal pancreatic masses and lymph nodes, to standardize an algorithm for their use and to consequently differentiate benign vs malignant pancreatic masses and evaluate lymph node involvement in a prospective multicenter design. Patients and methods The study design is prospective, blinded and multi-center, comparing endoscopic ultrasound elastography (EG-EUS) and contrast-enhnecement (CE-EUS) results for the characterization of focal pancreatic masses and lymph nodes by using parametric measurements, in comparison with the gold standard represented by pathology. The study will be performed with the approval of the institutional board (ethical committee) review of each center. The complete study protocol and particpating centers will be uploaded on ClinicalTrials.gov, the registry of federally and privately supported clinical trials conducted in the United States and around the world. Inclusion criteria Patients diagnosed with solid pancreatic tumor masses, with cytological / histo-logical confirmation Patients with or without suspected lymph node involvement are eligible Age 18 to 90 years old, men or women Signed informed consent for EG-EUS, CE-EUS and FNA biopsy Exclusion criteria Prior surgical treatment with curative intent or chemo-radiotherapy Patients diagnosed with mucin producing tumors, pancreatic cystic tumors, etc. Data collection • Personal data (name, surname, age, admission date, SSN, diagnosis at admission) Imaging tests All patients with a suspicion of pancreatic masses or lymph nodes should undergo EUS, with sequential EG-EUS and CE-EUS EUS with EUS-guided FNA and elastography Protocol of EUS with EUS-FNA should include linear EUS instruments with complete examinations of the pancreas. Tumor characteristics (echogenicity, echostructure, size) will be described as well as presence / absence of power Doppler signals. EUS-FNA will be performed in all pancreatic masses with at least three passes All examiners should be blinded for the results of pathology EG-EUS procedure: EUS-EG will be performed during usual EUS examinations, with two movies of 10 seconds recorded on the embedded HDD in order to minimize variability and to increase repeatability of acquisition. A two panel image with the usual conventional gray-scale B-mode EUS image on the right side and with the elastography image on the left side will be used. The same parameters will be set-up in all systems used: e-dynamic range 2, persistence 3, etc. The region of interest for EUS-EG will be preferably larger than the focal mass (approximately 50%-50%), in order to include the surrounding structures. If the focal mass is larger than 3 cm, part of the mass will be included in the ROI, as well as the surrounding structures (preferably avoiding large vessels). Very large ROI for the elastography calculations will be avoided due to the appearance of side artifacts. The following pre-settings will be used in all centers: elastography colour map 1, frame rejection 2, noise rejection 2, persistence 3, dynamic rage 4, smoothing 2, blend 50%. SR and SH will be measured; with three measurements made and recorded on the embedded HDD. For SR, the reference area should be placed at the same level with the lesion, if possible. CE-EUS procedure: A two panel image with the usual conventional gray-scale B-mode EUS image on the right side and with the contrast harmonic image on the left side will be used, according to pre-established presets. The starting point of the timer will be considered the moment of intravenous contrast injection (Sonovue 4.8 mL). CE-EUS will be performed during usual EUS examinations, with the whole movie (T0-T120s) recorded on the embedded HDD of the ultrasound system, for later analysis. A low mechanical index procedure (dynamic wide-band contrast harmo¬nic imaging mode) will be used, with a mechanical index of 0.2 and corresponding powers. The following pre-settings will be used in all centers: contrast mode dCHI-W, WPI-R/P (resolution / penetration for superficial vs deep structures), mechanical index (variable starting with 0.1, preferred 0.2), MI gray-scale (0.03), grey map 4, AGC 0, R-filter C, persistence 2, dynamic range 50, B-colour 21, smoothing 3, gamma curve linear. In order to minimize human bias, all post-processing and computer analysis of digital movies will be performed within the coordinating IT Center, with all programmers and statisticians being blinded to the clinical, imaging and pathological data. Off-line analysis of time-intensity curves will be performed using Vue-Box, which yields the following quantitative parameters: Peak Enhancement (PE), Wash-in Area Under the Curve (Wi-AUC), Rise Time (RT), mean Transit Time (mTT), Time To Peak (TTP), Wash-in Rate (WiR) and Wash-in Perfusion Index (WiPI). The software also provides referenced values (expressed in percentages), aligning the set of values for the tumor ROI to the parenchymal ones. Final diagnosis A positive cytological diagnosis will be taken as a final proof of malignancy of the pancreas mass or lymph node. The diagnoses obtained by EUS-FNA will be further verified either by surgery or during a clinical follow-up of at least 6 months. The diagnosis of chronic pancreatitis will be based on the clinical information (history of alcohol abuse, previous diagnosis of chronic pancreatitis or diabetes mellitus), as well as a combination of imaging methods (ultrasound, CT and EUS). At least four criteria of chronic pancreatitis during EUS will be considered for the positive diagnosis. The diagnosis of chronic pseudotumoral pancreatitis or benign lymph nodes will always be confirmed by surgery or by a follow-up of at least six months used to exclude malignancy in the patients that will not be operated on. Pathology samples obtained from duodeno-pancreatectomies or caudal pancreatecto-mies done with curative intent, as well as microhistological fragments obtained through EUS-FNA biopsy will be processed by paraffin embedding with usual stainings (haematoxylin-eosin), with subsequent immune-histochemistry at the discretion of the participating centers pathologists in order to exclude neuroendocrine tumors / pancreatic metastases. The patients will be followed-up for at least six months through clinical examination, biological exams and transabdominal ultrasound, eventually with a repeat spiral CT / EUS after six months. Statistical analysis Descriptive statistics All results will be expressed as mean ± standard deviation (SD). Differences between the patients with pancreatic cancer and chronic pancreatitis will performed by the two-sample t-test (two independent samples). Since this parametric method makes assumptions about normality and similar variances, we will initially perform both the Kolmogorov-Smirnov and Shapiro-Wilk W normality tests and verify the equality of variances assumption with the F test. In the case of the two-sample t-test, we will also perform the non-parametric alternative given by the Mann-Whitney U test, since in some instances it may even offer greater power to reject the null hypothesis than the t-test. Since with more than two groups of observations it is far better to use a single analysis that enables us to look at all the data in the same time, we will also perform the one-way analysis of variance (ANOVA) method with the same baseline assumptions. A p-value less than 0.05 will be considered as statistically significant. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EG-EUS and CE-EUS will be determined in comparison with the final diagnosis. Also, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for the subgroup of patients with negative EUS-FNA and a positive diagnosisi of malignancy during ensuing follow-up will be calculated separately. Power analysis The estimated number of patients included is at least 210, based on at least 10 centers with at least 20 patients each, which will be enrolled in a 12 months period. The power analysis was based on the following assumption: in order to use the powerful t-test for independent samples, a sample size equaling 105 patients in each group is sufficient to provide 95% statistical power to detect a difference of 5% in mean, for a type I error alpha = 0.05, and the population standard deviation = 10%. The difference in mean was based on previously published data which report an accuracy of approximately 80-85% for EUS-FNA, and 90% for EG-EUS and/or CE-EUS.
Official Title
-----------------
Real-time Semi-quantification of Endoscopic Ultrasound Elastography and Contrast-enhancement Using Strain Histograms (SH) and Contrast-enhancement (CE) for the Differentiation of Focal Pancreatic Masses and the Assessment of Lymph Node Involvement
Conditions
-----------------
Pancreatic Cancer, Secondary Malignant Neoplasm of Lymph Node, Benign Neoplasm of Lymph Nodes, Benign Pancreatic Tumors
Intervention / Treatment
-----------------
* Other: Elastography, contrast enhancement
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients diagnosed with solid pancreatic tumor masses, with cytological / histo-logical confirmation Patients with or without suspected lymph node involvement are eligible Age 18 to 90 years old, men or women Signed informed consent for EG-EUS, CE-EUS and FNA biopsy Exclusion Criteria: Prior surgical treatment with curative intent or chemo-radiotherapy Patients diagnosed with mucin producing tumors, pancreatic cystic tumors, etc.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pancreatic cancer<br>Consecutively admitted patients with pancreatic cancer confirmed by EUS-guided FNA. EG-EUS and CE-EUS will be applied in all patients. | Other: Elastography, contrast enhancement<br>* Elastography is an ultrasound method used for the reconstruction of tissue elasticity distribution in real-time. The main intended use is to differentiate between benign and malignant focal lesions based on the significantly smaller strain of the latter real time. Tissue elastography can be easily performed with conventional probes, including the linear EUS probes used for the examination of the pancreas and/or lymph nodes. Contrast-enhancement Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use for diagnostic imaging. Pancreatic adenocarcinomas are usually hypovascular tumors.<br>|
| Benign pancreatic masses<br>Consecutively admitted patients with benign pancreatic masses with negative EUS-guided FNA. EG-EUS and CE-EUS will be applied in all patients. | Other: Elastography, contrast enhancement<br>* Elastography is an ultrasound method used for the reconstruction of tissue elasticity distribution in real-time. The main intended use is to differentiate between benign and malignant focal lesions based on the significantly smaller strain of the latter real time. Tissue elastography can be easily performed with conventional probes, including the linear EUS probes used for the examination of the pancreas and/or lymph nodes. Contrast-enhancement Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use for diagnostic imaging. Pancreatic adenocarcinomas are usually hypovascular tumors.<br>|
| Malignant lymph nodes<br>Consecutively admitted patients with malignant lymphnodes confirmed by EUS-guided FNA. EG-EUS will be applied in all patients. | Other: Elastography, contrast enhancement<br>* Elastography is an ultrasound method used for the reconstruction of tissue elasticity distribution in real-time. The main intended use is to differentiate between benign and malignant focal lesions based on the significantly smaller strain of the latter real time. Tissue elastography can be easily performed with conventional probes, including the linear EUS probes used for the examination of the pancreas and/or lymph nodes. Contrast-enhancement Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use for diagnostic imaging. Pancreatic adenocarcinomas are usually hypovascular tumors.<br>|
| Benign lymph nodes<br>Consecutively admitted patients with benign lymphnodes with negative EUS-guided FNA. EG-EUS will be applied in all patients. | Other: Elastography, contrast enhancement<br>* Elastography is an ultrasound method used for the reconstruction of tissue elasticity distribution in real-time. The main intended use is to differentiate between benign and malignant focal lesions based on the significantly smaller strain of the latter real time. Tissue elastography can be easily performed with conventional probes, including the linear EUS probes used for the examination of the pancreas and/or lymph nodes. Contrast-enhancement Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use for diagnostic imaging. Pancreatic adenocarcinomas are usually hypovascular tumors.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Strain histogram and contrast enhancement during EUS in pancreatic masses and lymph nodes | | 12 months |
|
|||
NCT01093157
|
A Dose Escalation Study of Long-acting ACTH Gel in Membranous Nephropathy
|
Membranous Nephropathy (MN) is an immune-mediated kidney disease that affects the glomerulus or the filter that removes toxins from the blood. Damage to the membrane that separates blood from urine results in loss of protein into the urine (proteinuria) and in some cases loss of kidney function.There is no standard specific treatment for MN.~ACTH has a pronounced lipid-lowering effect in healthy individuals, in steroid-treated patients with renal disease and in hemodialysis patients Some studies suggest that prolonged synthetic ACTH therapy may represent an effective therapy in patients with idiopathic MN, more extensive randomized studies with longer follow-up are needed before therapeutic recommendations can be made.~We propose to do a pilot study to test the hypothesis that biologic ACTH, a slow-release formulation of corticotropin extracted from porcine pituitary glands (H.P. Acthar gel) will be effective in reducing proteinuria and improving lipid profile in patients with idiopathic MN.
|
A Dose-finding Pilot Study of ACTH (Adrenocorticotropic Hormone) on the Proteinuria and Serum Lipoprotein Profile in Patients With Idiopathic Membranous Nephropathy (MN)
|
Glomerulonephritis
|
* Drug: Adrenocorticotrophic hormone ACTH
|
Inclusion Criteria:• Idiopathic MN with diagnostic biopsy performed less than 36 months from the time of dose randomization.~Patients need to be treated with an ACEI and/or ARB, for at least 3 months prior to ACTH treatment and have adequately controlled blood pressure (BP <130/75 mm Hg in >75% of the readings). Patients with documented evidence of >3 months treatment with maximal Ang II blockade, target BP (BP <130/75 mm Hg in >75% of the readings) and who remain with proteinuria >4.0g/24h may enter the ACTH phase of the study without the need to have the run-in/conservative phase of the study.~Proteinuria as measured by Uprot/Ucr > 4.0 on a spot sample aliquot from a 24-hour urine collection. The choice of Uprot/UCr is in accord with recent NKF-CKD guidelines.[9]~Estimated GFR ≥ 40 ml/min/1.73m2 while taking ACEI/ARB therapy. The GFR will be estimated using the 4 variable MDRD equation as published in the NKF-CKD guidelines.[9] The same NKF-CKD guidelines also promote the use of estimated GFR (GFRest) values rather than serum creatinine levels or CrCl measurements as the preferred non-invasive method of determining glomerular filtration rates.[9]~Exclusion Criteria:• Age <18 years.~Estimated GFR < 40 ml/min/1.73m2, or serum creatinine >2.0 mg/dl.~Renal biopsy showing more than 30% glomerulosclerosis and/or tubular atrophy.~Patient must be off glucocorticoid, calcineurin inhibitors (cyclosporin A, tacrolimus) or mycophenolic mofetil for > 1 month, and alkylating agents or rituximab for >6 months.~Resistance to the following immunosuppressive routines e.g. steroids alone, calcineurin inhibitors plus or minus steroids, cytotoxic agents plus or minus steroids.~Patients with active infections or secondary causes of MN (e.g. hepatitis B, SLE, medications, malignancies). Testing for HIV, Hepatitis B and C should have occurred < 2 years prior to enrollment into the study.~Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy. Patients who have recent history of steroid induced diabetes but no evidence on renal biopsy performed within 6 months of entry into the study are eligible for enrollment.~Pregnancy or nursing - for safety reasons.~Acute renal vein thrombosis documented prior to entry by renal US or CT scan and requiring anticoagulation therapy.
|
18 Years
|
72 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in proteinuria from baseline to value at 3 months . | | 3 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission(CR) or Partial Remission (PR) at 3 months | Definition of proteinuric status. UP = urinary protein (g/24h) Complete remission (CR) UP ≤ 0.3 g Partial remission (PR) Reduction in UP of > 50% plus final UP ≤ 3.5 g but >0.3g Non-response (NR) Reduction in UP of < 50%. (includes increase in UP <50%) Progression Proteinuria increases by > 50% | 3 months |
| Adverse effects | Patients will be directly questioned every two weeks during the drug exposure and then at monthly intervals during follow-up. In addition a contact number will be provided to the subjects to call if they experience any adverse affect or if they suspect adverse effect at any time between specific visits | Throughout three months of this study and for nine months follow-up |
|
Kidney disease, Glomerulonephritis
|
Hormones, Adrenocorticotropic Hormone, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACTH (HP Acthar gel) 40 units<br> | Drug: Adrenocorticotrophic hormone ACTH<br>* There will be two arms to the study: one arm receive 40 units and the second arm 80 units of the ACTH gel subcutaneously both given in a dose escalating frequency beginning at once every two weeks escalating to a maximum of twice per week over a total of three months exposed.An ammendment(approved by Health Canada and the UHN IRB allows an additional 1 month of the perscribed therapy of ACTH )if there is an improvement in proteinuria at the end of the 3 month exposure.<br>* Other names: HP Acthar gel;|
| Active Comparator: ACTH (HP Acthar gel) 80 units<br> | Drug: Adrenocorticotrophic hormone ACTH<br>* There will be two arms to the study: one arm receive 40 units and the second arm 80 units of the ACTH gel subcutaneously both given in a dose escalating frequency beginning at once every two weeks escalating to a maximum of twice per week over a total of three months exposed.An ammendment(approved by Health Canada and the UHN IRB allows an additional 1 month of the perscribed therapy of ACTH )if there is an improvement in proteinuria at the end of the 3 month exposure.<br>* Other names: HP Acthar gel;|
|
A Dose Escalation Study of Long-acting ACTH Gel in Membranous Nephropathy
Study Overview
=================
Brief Summary
-----------------
Membranous Nephropathy (MN) is an immune-mediated kidney disease that affects the glomerulus or the filter that removes toxins from the blood. Damage to the membrane that separates blood from urine results in loss of protein into the urine (proteinuria) and in some cases loss of kidney function.There is no standard specific treatment for MN. ACTH has a pronounced lipid-lowering effect in healthy individuals, in steroid-treated patients with renal disease and in hemodialysis patients Some studies suggest that prolonged synthetic ACTH therapy may represent an effective therapy in patients with idiopathic MN, more extensive randomized studies with longer follow-up are needed before therapeutic recommendations can be made. We propose to do a pilot study to test the hypothesis that biologic ACTH, a slow-release formulation of corticotropin extracted from porcine pituitary glands (H.P. Acthar gel) will be effective in reducing proteinuria and improving lipid profile in patients with idiopathic MN.
Official Title
-----------------
A Dose-finding Pilot Study of ACTH (Adrenocorticotropic Hormone) on the Proteinuria and Serum Lipoprotein Profile in Patients With Idiopathic Membranous Nephropathy (MN)
Conditions
-----------------
Glomerulonephritis
Intervention / Treatment
-----------------
* Drug: Adrenocorticotrophic hormone ACTH
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria:• Idiopathic MN with diagnostic biopsy performed less than 36 months from the time of dose randomization. Patients need to be treated with an ACEI and/or ARB, for at least 3 months prior to ACTH treatment and have adequately controlled blood pressure (BP <130/75 mm Hg in >75% of the readings). Patients with documented evidence of >3 months treatment with maximal Ang II blockade, target BP (BP <130/75 mm Hg in >75% of the readings) and who remain with proteinuria >4.0g/24h may enter the ACTH phase of the study without the need to have the run-in/conservative phase of the study. Proteinuria as measured by Uprot/Ucr > 4.0 on a spot sample aliquot from a 24-hour urine collection. The choice of Uprot/UCr is in accord with recent NKF-CKD guidelines.[9] Estimated GFR ≥ 40 ml/min/1.73m2 while taking ACEI/ARB therapy. The GFR will be estimated using the 4 variable MDRD equation as published in the NKF-CKD guidelines.[9] The same NKF-CKD guidelines also promote the use of estimated GFR (GFRest) values rather than serum creatinine levels or CrCl measurements as the preferred non-invasive method of determining glomerular filtration rates.[9] Exclusion Criteria:• Age <18 years. Estimated GFR < 40 ml/min/1.73m2, or serum creatinine >2.0 mg/dl. Renal biopsy showing more than 30% glomerulosclerosis and/or tubular atrophy. Patient must be off glucocorticoid, calcineurin inhibitors (cyclosporin A, tacrolimus) or mycophenolic mofetil for > 1 month, and alkylating agents or rituximab for >6 months. Resistance to the following immunosuppressive routines e.g. steroids alone, calcineurin inhibitors plus or minus steroids, cytotoxic agents plus or minus steroids. Patients with active infections or secondary causes of MN (e.g. hepatitis B, SLE, medications, malignancies). Testing for HIV, Hepatitis B and C should have occurred < 2 years prior to enrollment into the study. Type 1 or 2 diabetes mellitus: to exclude proteinuria secondary to diabetic nephropathy. Patients who have recent history of steroid induced diabetes but no evidence on renal biopsy performed within 6 months of entry into the study are eligible for enrollment. Pregnancy or nursing - for safety reasons. Acute renal vein thrombosis documented prior to entry by renal US or CT scan and requiring anticoagulation therapy.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 72 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACTH (HP Acthar gel) 40 units<br> | Drug: Adrenocorticotrophic hormone ACTH<br>* There will be two arms to the study: one arm receive 40 units and the second arm 80 units of the ACTH gel subcutaneously both given in a dose escalating frequency beginning at once every two weeks escalating to a maximum of twice per week over a total of three months exposed.An ammendment(approved by Health Canada and the UHN IRB allows an additional 1 month of the perscribed therapy of ACTH )if there is an improvement in proteinuria at the end of the 3 month exposure.<br>* Other names: HP Acthar gel;|
| Active Comparator: ACTH (HP Acthar gel) 80 units<br> | Drug: Adrenocorticotrophic hormone ACTH<br>* There will be two arms to the study: one arm receive 40 units and the second arm 80 units of the ACTH gel subcutaneously both given in a dose escalating frequency beginning at once every two weeks escalating to a maximum of twice per week over a total of three months exposed.An ammendment(approved by Health Canada and the UHN IRB allows an additional 1 month of the perscribed therapy of ACTH )if there is an improvement in proteinuria at the end of the 3 month exposure.<br>* Other names: HP Acthar gel;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in proteinuria from baseline to value at 3 months . | | 3 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission(CR) or Partial Remission (PR) at 3 months | Definition of proteinuric status. UP = urinary protein (g/24h) Complete remission (CR) UP ≤ 0.3 g Partial remission (PR) Reduction in UP of > 50% plus final UP ≤ 3.5 g but >0.3g Non-response (NR) Reduction in UP of < 50%. (includes increase in UP <50%) Progression Proteinuria increases by > 50% | 3 months |
| Adverse effects | Patients will be directly questioned every two weeks during the drug exposure and then at monthly intervals during follow-up. In addition a contact number will be provided to the subjects to call if they experience any adverse affect or if they suspect adverse effect at any time between specific visits | Throughout three months of this study and for nine months follow-up |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Kidney disease, Glomerulonephritis
|
|
NCT01902290
|
Study of Efficacy and Safety of Brodalumab Compared With Placebo in Adults With Inadequately Controlled Asthma With High Bronchodilator Reversibility
|
The purpose of this study is to determine if brodalumab (AMG 827) is safe and effective compared to placebo as measured by change in Asthma Control Questionnaire (ACQ) composite scores.
|
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Brodalumab in Subjects With Inadequately Controlled Asthma and High Bronchodilator Reversibility
|
Asthma
|
* Biological: Placebo
* Biological: Brodalumab
|
Inclusion Criteria:~Diagnosis of asthma, and presently has reversibility over pre-bronchodilator forced expiratory volume in 1 second (FEV1) of ≥ 20% at screening~Percent of predicted FEV1 ≥ 40% and ≤ 80% at screening~Inhaled corticosteroid (ICS) ≥ 200 and ≤ 1000/μg/day fluticasone powder or equivalent~Ongoing asthma symptoms with asthma control questionnaire (ACQ) composite score at screening and baseline ≥ 1.5 points~Exclusion Criteria:~History of chronic obstructive pulmonary disease (COPD) or other chronic pulmonary condition other than asthma~History of allergic bronchopulmonary aspergillosis~Respiratory infection within 4 weeks of screening or 1 week of baseline visit~Subject has known history of Crohn's disease~Subject has any other significant concurrent medical condition of laboratory abnormalities, as defined in the study protocol~Subject has previously used any anti-interleukin-17 (IL17) biologic therapy~Subject is pregnant or breastfeeding, or planning to become pregnant while enrolled in the study~Female subject is unwilling to use highly effective methods of birth control unless 2 years post-menopausal or surgically sterile~Subject has severe depression measured by Personal Health Questionnaire Depression Scale (PHQ-8) or suicidal ideation/behavior as measured by and Columbia Suicide Severity Rating Scale (e-CSSRS)~Subject has a history or evidence of psychiatric disorder or substance abuse considered by the Investigator to pose a risk to subject safety
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Score at Week 24 | The ACQ is a validated instrument used in clinical research and practice to evaluate asthma control/impairment.~The ACQ assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon wakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and FEV1. All seven items are scored on a 7-point scale, with 0 indicating good control and 6 indicating poor control; the total score is the mean of the seven items and ranges from 0 (totally-controlled) to 6 (extremely poorly controlled). A negative change from baseline indicates improvement. A change of 0.50 points is considered clinically meaningful and a total score of < 1.0 indicates good asthma control. | Baseline and week 24 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Exacerbation Rate | The asthma exacerbation event rate is defined as the number of events per subject-year during the 24 week treatment period. An asthma exacerbation was defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study; distinct asthma exacerbations were defined as events with start dates more than 10 days apart from each other. | Baseline to week 24 |
| Change From Baseline in ACQ Composite Score at Week 24 in ICS+LABA Subpopulation | The ACQ is a validated instrument used in clinical research and practice to evaluate asthma control/impairment.~The ACQ assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon wakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and FEV1. All seven items are scored on a 7-point scale, with 0 indicating good control and 6 indicating poor control; the total score is the mean of the seven items and ranges from 0 (totally-controlled) to 6 (extremely poorly controlled). A negative change from baseline indicates improvement. A change of 0.50 points is considered clinically meaningful and a total score of < 1.0 indicates good asthma control. | Baseline and week 24 |
| Asthma Exacerbation Rate in ICS+LABA Subpopulation | The asthma exacerbation event rate is defined as the number of events per subject-year during the 24 week treatment period. An asthma exacerbation was defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study; distinct asthma exacerbations were defined as events with start dates more than 10 days apart from each other. | Baseline to week 24 |
| Change From Baseline in Daily Asthma Symptom Score (7-day Average Score) | The Asthma Symptom Diary (ASD) consists of 23 questions answered on a handheld device, including 10 asthma symptom-related items (5 answered in the morning and 5 in the evening).~The morning diary comprises questions on 4 asthma-related symptoms (wheezing, shortness of breath, cough, chest tightness), rated on a 5-point severity scale from 0 (no symptom) to 4 (very severe symptoms), and 1 question on nocturnal awakenings, rated from 0 (did not wake up) to 4 (unable to sleep due to asthma). The evening diary has questions on the same 4 asthma-related symptoms and 1 question on limitations of activities, rated from 0 (not at all) to 4 (extremely).~The ASD daily score is computed by averaging the responses to the 10 symptom-related items, and the mean 7-day ASD score is calculated by averaging the 7 daily scores, with the final score ranging from 0 (minimal symptoms) to 4 (very severe symptoms). | Baseline and week 24 |
| Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) | | Baseline and week 24 |
| Change From Baseline in Daily Rescue Short-acting Beta-agonist Use | Participants were permitted allowed to use their inhaled rescue medication (SABA) as needed throughout the study and the use was captured in the daily electronic diary (eDiary). | Baseline and week 24 |
| Time to First Asthma Exacerbation | An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study. Median time to first asthma exacerbation could not be estimated, the percentage of participants with an asthma exacerbation is reported. | From first dose of study drug to week 24 |
| Number of Participants Who Experienced an Asthma Exacerbation | An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study. | Baseline to week 24 |
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Overall Score | The AQLQ is an asthma-specific instrument that includes evaluations of both symptoms and health-related quality of life measures. The 32-item instrument measures 4 domains affected by asthma including activity limitations, emotional function, exposure to environmental stimuli, and symptoms.~Participants were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (7=no impairment, 1=severe impairment). The overall score was calculated as mean of the responses to the 32 questions and ranges from 1 (severe impairment) to 7 (no impairment). A positive change from baseline indicates improvement. | Baseline and week 24 |
| Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) | Peak expiratory flow rate was measured by the participant twice daily at approximately the same time each day (eg, within 1 hour of waking and immediately before bedtime) using a peak flow meter. | Baseline and week 24 |
| Change From Baseline in Variation of Peak Flow | Peak flow was measured by the participant twice daily at approximately the same time each day (eg, within 1 hour of waking and immediately before bedtime) using a peak flow meter. The variation of peak flow is defined as the absolute value of the difference between the A.M. and P.M. peak flow in one day for an individual participant. | Baseline and week 24 |
| Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Asthma symptom-free days is defined as days that a participant had a score of zero in their daily asthma symptom diary score.~The ASD consists of 23 questions answered on a handheld device, including 10 asthma symptom-related items (5 answered in the morning and 5 in the evening).~The morning diary comprises questions on 4 asthma-related symptoms (wheezing, shortness of breath, cough, chest tightness), rated on a 5-point severity scale from 0 (no symptom) to 4 (very severe symptoms), and 1 question on nocturnal awakenings, rated from 0 (did not wake up) to 4 (unable to sleep due to asthma). The evening diary has questions on the same 4 asthma-related symptoms and 1 question on limitations of activities, rated from 0 (not at all) to 4 (extremely).~The daily score is the average of the responses to the 10 items. | Baseline (the 4 weeks prior to first dose) and 4-week intervals up to week 24 |
| Serum Brodalumab Concentration | Serum brodalumab concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) = 0.0500 µg/mL; values below the LLOQ were set to zero. | Day 1 and weeks 1, 2, 4, 8, 12, 16, and 22 at predose, week 2 + 3 days, week 22 + 3, 7, 10, and 14 days |
|
Inadequately controlled asthma, brodalumab, AMG 827
|
Brodalumab, Dermatologic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo administered by subcutaneous injection on day 1, week 1, week 2 and every 2 weeks thereafter for 24 weeks. | Biological: Placebo<br>* Placebo administered subcutaneously<br>|
| Experimental: Brodalumab 210 mg<br>Participants received 210 mg brodalumab administered by subcutaneous injection on day 1, week 1, week 2, and every 2 weeks thereafter for 24 weeks. | Biological: Brodalumab<br>* Brodalumab administered subcutaneously<br>* Other names: AMG 827;|
|
Study of Efficacy and Safety of Brodalumab Compared With Placebo in Adults With Inadequately Controlled Asthma With High Bronchodilator Reversibility
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if brodalumab (AMG 827) is safe and effective compared to placebo as measured by change in Asthma Control Questionnaire (ACQ) composite scores.
Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Brodalumab in Subjects With Inadequately Controlled Asthma and High Bronchodilator Reversibility
Conditions
-----------------
Asthma
Intervention / Treatment
-----------------
* Biological: Placebo
* Biological: Brodalumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of asthma, and presently has reversibility over pre-bronchodilator forced expiratory volume in 1 second (FEV1) of ≥ 20% at screening Percent of predicted FEV1 ≥ 40% and ≤ 80% at screening Inhaled corticosteroid (ICS) ≥ 200 and ≤ 1000/μg/day fluticasone powder or equivalent Ongoing asthma symptoms with asthma control questionnaire (ACQ) composite score at screening and baseline ≥ 1.5 points Exclusion Criteria: History of chronic obstructive pulmonary disease (COPD) or other chronic pulmonary condition other than asthma History of allergic bronchopulmonary aspergillosis Respiratory infection within 4 weeks of screening or 1 week of baseline visit Subject has known history of Crohn's disease Subject has any other significant concurrent medical condition of laboratory abnormalities, as defined in the study protocol Subject has previously used any anti-interleukin-17 (IL17) biologic therapy Subject is pregnant or breastfeeding, or planning to become pregnant while enrolled in the study Female subject is unwilling to use highly effective methods of birth control unless 2 years post-menopausal or surgically sterile Subject has severe depression measured by Personal Health Questionnaire Depression Scale (PHQ-8) or suicidal ideation/behavior as measured by and Columbia Suicide Severity Rating Scale (e-CSSRS) Subject has a history or evidence of psychiatric disorder or substance abuse considered by the Investigator to pose a risk to subject safety
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo administered by subcutaneous injection on day 1, week 1, week 2 and every 2 weeks thereafter for 24 weeks. | Biological: Placebo<br>* Placebo administered subcutaneously<br>|
| Experimental: Brodalumab 210 mg<br>Participants received 210 mg brodalumab administered by subcutaneous injection on day 1, week 1, week 2, and every 2 weeks thereafter for 24 weeks. | Biological: Brodalumab<br>* Brodalumab administered subcutaneously<br>* Other names: AMG 827;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Score at Week 24 | The ACQ is a validated instrument used in clinical research and practice to evaluate asthma control/impairment. The ACQ assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon wakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and FEV1. All seven items are scored on a 7-point scale, with 0 indicating good control and 6 indicating poor control; the total score is the mean of the seven items and ranges from 0 (totally-controlled) to 6 (extremely poorly controlled). A negative change from baseline indicates improvement. A change of 0.50 points is considered clinically meaningful and a total score of < 1.0 indicates good asthma control. | Baseline and week 24 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Exacerbation Rate | The asthma exacerbation event rate is defined as the number of events per subject-year during the 24 week treatment period. An asthma exacerbation was defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study; distinct asthma exacerbations were defined as events with start dates more than 10 days apart from each other. | Baseline to week 24 |
| Change From Baseline in ACQ Composite Score at Week 24 in ICS+LABA Subpopulation | The ACQ is a validated instrument used in clinical research and practice to evaluate asthma control/impairment. The ACQ assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon wakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and FEV1. All seven items are scored on a 7-point scale, with 0 indicating good control and 6 indicating poor control; the total score is the mean of the seven items and ranges from 0 (totally-controlled) to 6 (extremely poorly controlled). A negative change from baseline indicates improvement. A change of 0.50 points is considered clinically meaningful and a total score of < 1.0 indicates good asthma control. | Baseline and week 24 |
| Asthma Exacerbation Rate in ICS+LABA Subpopulation | The asthma exacerbation event rate is defined as the number of events per subject-year during the 24 week treatment period. An asthma exacerbation was defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study; distinct asthma exacerbations were defined as events with start dates more than 10 days apart from each other. | Baseline to week 24 |
| Change From Baseline in Daily Asthma Symptom Score (7-day Average Score) | The Asthma Symptom Diary (ASD) consists of 23 questions answered on a handheld device, including 10 asthma symptom-related items (5 answered in the morning and 5 in the evening). The morning diary comprises questions on 4 asthma-related symptoms (wheezing, shortness of breath, cough, chest tightness), rated on a 5-point severity scale from 0 (no symptom) to 4 (very severe symptoms), and 1 question on nocturnal awakenings, rated from 0 (did not wake up) to 4 (unable to sleep due to asthma). The evening diary has questions on the same 4 asthma-related symptoms and 1 question on limitations of activities, rated from 0 (not at all) to 4 (extremely). The ASD daily score is computed by averaging the responses to the 10 symptom-related items, and the mean 7-day ASD score is calculated by averaging the 7 daily scores, with the final score ranging from 0 (minimal symptoms) to 4 (very severe symptoms). | Baseline and week 24 |
| Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) | | Baseline and week 24 |
| Change From Baseline in Daily Rescue Short-acting Beta-agonist Use | Participants were permitted allowed to use their inhaled rescue medication (SABA) as needed throughout the study and the use was captured in the daily electronic diary (eDiary). | Baseline and week 24 |
| Time to First Asthma Exacerbation | An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study. Median time to first asthma exacerbation could not be estimated, the percentage of participants with an asthma exacerbation is reported. | From first dose of study drug to week 24 |
| Number of Participants Who Experienced an Asthma Exacerbation | An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study. | Baseline to week 24 |
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Overall Score | The AQLQ is an asthma-specific instrument that includes evaluations of both symptoms and health-related quality of life measures. The 32-item instrument measures 4 domains affected by asthma including activity limitations, emotional function, exposure to environmental stimuli, and symptoms. Participants were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (7=no impairment, 1=severe impairment). The overall score was calculated as mean of the responses to the 32 questions and ranges from 1 (severe impairment) to 7 (no impairment). A positive change from baseline indicates improvement. | Baseline and week 24 |
| Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) | Peak expiratory flow rate was measured by the participant twice daily at approximately the same time each day (eg, within 1 hour of waking and immediately before bedtime) using a peak flow meter. | Baseline and week 24 |
| Change From Baseline in Variation of Peak Flow | Peak flow was measured by the participant twice daily at approximately the same time each day (eg, within 1 hour of waking and immediately before bedtime) using a peak flow meter. The variation of peak flow is defined as the absolute value of the difference between the A.M. and P.M. peak flow in one day for an individual participant. | Baseline and week 24 |
| Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Asthma symptom-free days is defined as days that a participant had a score of zero in their daily asthma symptom diary score. The ASD consists of 23 questions answered on a handheld device, including 10 asthma symptom-related items (5 answered in the morning and 5 in the evening). The morning diary comprises questions on 4 asthma-related symptoms (wheezing, shortness of breath, cough, chest tightness), rated on a 5-point severity scale from 0 (no symptom) to 4 (very severe symptoms), and 1 question on nocturnal awakenings, rated from 0 (did not wake up) to 4 (unable to sleep due to asthma). The evening diary has questions on the same 4 asthma-related symptoms and 1 question on limitations of activities, rated from 0 (not at all) to 4 (extremely). The daily score is the average of the responses to the 10 items. | Baseline (the 4 weeks prior to first dose) and 4-week intervals up to week 24 |
| Serum Brodalumab Concentration | Serum brodalumab concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) = 0.0500 µg/mL; values below the LLOQ were set to zero. | Day 1 and weeks 1, 2, 4, 8, 12, 16, and 22 at predose, week 2 + 3 days, week 22 + 3, 7, 10, and 14 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inadequately controlled asthma, brodalumab, AMG 827
|
|
NCT02020213
|
Posaconazole as Salvage Therapy for Aspergillus Pulmonary Infection.
|
Invasive Aspergillus infection (IAI) occasionally occurs in immunocompromised people. Except administrating empirical anti-fungal agent, using objective parameters to support the tentative diagnosis of an IAI in order to make the anti-fungal treatment more specifically is also important. At present, serum galactomannan (GM) test is the less-invasive, non-cultural, and time-saving examination for augmenting a diagnosis of Aspergillosis. It was suggested by Infectious Disease Society of America (IDSA) 2008 as a screening and monitoring tool for Aspergillosis , and the cut-off value was adjusted to 0.5 by USA FDA . However, in clinical practice, GM seems not to have good predicted value even the sensitivity and specificity are declaimed more than 80% . Other controversial issues include the reproducibility of GM5 and the effect of piperacillin-tazobactam or other antibiotics on the accuracy of GM baseline In this study, serum GMs are examined in two conditions, one is collected for establishing a baseline and the other is collected after piperacillin-tazobactam administration. We hope to confirm the validity of GM baseline and the effect of piperacillin-tazobactam on GM value in Taiwan.
|
We try to enroll patient who are followed in hematology department in TCVGH and are diagnosed as probable pulmonary Aspergillus infection or proven pulmonary Aspergillus infection. If they have poor response to current thought effective agent for pulmonary Aspergillus (eg, amphotericin B, Voriconazole, itraconazole) 2 weeks, then they can choose to receive Posaconazole as salvage therapy in our study. However, our study wants to quantification of therapeutic response, so the enrolled patient should be agree to let us check serum galactomannan level at beginning and per 2 weeks. They also should be receive chest CT in the beginning and in the end of posaconazole treatment. The rule out timing is evaluated by clinical doctors (hematology department) per 2 weeks, if posaconazole has poor effect to their disease, the clinical doctors can decided to terminate posaconazole administration. Another effective agent will be given when posaconazole fails.
|
Effectiveness of Posaconazole as Salvage Treatment After 2 Weeks of Preemptive Antifungal Treatment
|
Clinical Infection
|
* Drug: Posaconazole
|
Inclusion Criteria:~Taichung Veterans General Hospital Hematology and Oncology patients with pulmonary aspergillosis, the preliminary use of effective anti-Aspergillus drugs (including amphotericin B, itraconazole, or voriconazole) 14 days later, the symptoms worsen or improve, or can not tolerate the side effects.~The default number of subjects 12.~Exclusion Criteria:~Children, minors, pregnant women, newborns, prisoners, mental illness, loss of adult decision-making capacity due to illness, the Aboriginal ... and other vulnerable groups, and critically ill patients
|
20 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical response | fever subsides (< 38 C) dyspnea improves ( evaluate by clinical doctors) CXR improves | per 2 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum galactomannan level | follow the galactomannan level and check if it corresponds to clinical response or not. | per 2 weeks |
|
successful percentage
|
Posaconazole, Antifungal Agents, Anti-Infective Agents, Trypanocidal Agents, Antiprotozoal Agents, Antiparasitic Agents, 14-alpha Demethylase Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Steroid Synthesis Inhibitors, Hormone Antagonists, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Posaconazole, salvage<br>Posaconazole, per oral , 400 mg, bid , 8 weeks. | Drug: Posaconazole<br>* 400 mg po bid for 8 weeks<br>* Other names: posanol;|
|
Posaconazole as Salvage Therapy for Aspergillus Pulmonary Infection.
Study Overview
=================
Brief Summary
-----------------
Invasive Aspergillus infection (IAI) occasionally occurs in immunocompromised people. Except administrating empirical anti-fungal agent, using objective parameters to support the tentative diagnosis of an IAI in order to make the anti-fungal treatment more specifically is also important. At present, serum galactomannan (GM) test is the less-invasive, non-cultural, and time-saving examination for augmenting a diagnosis of Aspergillosis. It was suggested by Infectious Disease Society of America (IDSA) 2008 as a screening and monitoring tool for Aspergillosis , and the cut-off value was adjusted to 0.5 by USA FDA . However, in clinical practice, GM seems not to have good predicted value even the sensitivity and specificity are declaimed more than 80% . Other controversial issues include the reproducibility of GM5 and the effect of piperacillin-tazobactam or other antibiotics on the accuracy of GM baseline In this study, serum GMs are examined in two conditions, one is collected for establishing a baseline and the other is collected after piperacillin-tazobactam administration. We hope to confirm the validity of GM baseline and the effect of piperacillin-tazobactam on GM value in Taiwan.
Detailed Description
-----------------
We try to enroll patient who are followed in hematology department in TCVGH and are diagnosed as probable pulmonary Aspergillus infection or proven pulmonary Aspergillus infection. If they have poor response to current thought effective agent for pulmonary Aspergillus (eg, amphotericin B, Voriconazole, itraconazole) 2 weeks, then they can choose to receive Posaconazole as salvage therapy in our study. However, our study wants to quantification of therapeutic response, so the enrolled patient should be agree to let us check serum galactomannan level at beginning and per 2 weeks. They also should be receive chest CT in the beginning and in the end of posaconazole treatment. The rule out timing is evaluated by clinical doctors (hematology department) per 2 weeks, if posaconazole has poor effect to their disease, the clinical doctors can decided to terminate posaconazole administration. Another effective agent will be given when posaconazole fails.
Official Title
-----------------
Effectiveness of Posaconazole as Salvage Treatment After 2 Weeks of Preemptive Antifungal Treatment
Conditions
-----------------
Clinical Infection
Intervention / Treatment
-----------------
* Drug: Posaconazole
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Taichung Veterans General Hospital Hematology and Oncology patients with pulmonary aspergillosis, the preliminary use of effective anti-Aspergillus drugs (including amphotericin B, itraconazole, or voriconazole) 14 days later, the symptoms worsen or improve, or can not tolerate the side effects. The default number of subjects 12. Exclusion Criteria: Children, minors, pregnant women, newborns, prisoners, mental illness, loss of adult decision-making capacity due to illness, the Aboriginal ... and other vulnerable groups, and critically ill patients
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Posaconazole, salvage<br>Posaconazole, per oral , 400 mg, bid , 8 weeks. | Drug: Posaconazole<br>* 400 mg po bid for 8 weeks<br>* Other names: posanol;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical response | fever subsides (< 38 C) dyspnea improves ( evaluate by clinical doctors) CXR improves | per 2 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum galactomannan level | follow the galactomannan level and check if it corresponds to clinical response or not. | per 2 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
successful percentage
|
NCT02654327
|
pRotective vEntilation With Veno-venouS Lung assisT in Respiratory Failure
|
This is a trial of a new way of treating patients with respiratory failure. The investigators propose to deliver a multi-centre clinical trial to determine whether veno-venous extracorporeal carbon dioxide removal (VV-ECCO2R) and lower tidal volume mechanical ventilation improves outcomes and is cost-effective, in comparison with standard care in patients who are mechanically ventilated for acute hypoxaemic respiratory failure
|
Acute hypoxaemic respiratory failure requiring mechanical ventilation is a major cause of morbidity and mortality. A significant proportion of affected patients will have the Acute Respiratory Distress Syndrome (ARDS). Mechanical ventilation is often required to provide adequate gas exchange and although it is life-saving in this setting, it is also now known to contribute to the morbidity and mortality in the condition. Ventilators delivering high pressures and volumes cause regional over distension in the injured lung resulting in further inflammation and non-cardiogenic pulmonary oedema. The release of inflammatory mediators from the damaged lung causes systemic inflammation leading to multi-organ failure and death.~The few interventions that have been shown to reduce the high mortality in these patients have targeted ventilator-induced lung injury (VILI). A landmark trial by the ARDSNet trials group found that ventilating patients with acute hypoxaemic respiratory failure secondary to ARDS with a lung protective strategy aiming for a reduced tidal volume of 6ml/kg predicted body weight (PBW) and a maximum end-inspiratory plateau pressure (Pplat) ≤ 30cmH2O decreased mortality from 40% (in the conventional arm treated with tidal volume less than 12ml/kg PBW) to 31%.~Extracorporeal carbon dioxide removal (ECCO2R) in association with mechanical ventilation offers a potentially attractive solution to permit tidal volume reduction to less than 6ml/kg PBW and to achieve low plateau pressures (< 25cmH2O). Using these extracorporeal circuits, carbon dioxide can be 'dialysed' out of the blood while the lungs are ventilated in a more protective manner. In recent years, more efficient veno-venous devices have become available. These have replaced arterio-venous devices and have the advantage of not requiring arterial puncture. These can achieve carbon dioxide removal with relatively low extracorporeal blood flows (0.4-1 l/min) requiring only a smaller dual lumen venous catheter. In addition these ECCO2R devices use more biocompatible materials making the device more resistant to clot formation and cause less platelet and clotting factor consumption. Therefore only minimal systemic anticoagulation is required which reduces the likelihood of bleeding complications. These devices are now comparable to renal dialysis equipment, which is routinely used safely as standard care in ICUs in the United Kingdom.~Together this highlights the need for a large randomised controlled trial to establish whether VV-ECCO2R in acute hypoxaemic respiratory failure can allow the use of a more protective ventilatory strategy and is associated with improved patient outcomes. Importantly, if there was no benefit, the trial would provide evidence to stop the widespread adoption of an expensive and ineffective or potentially harmful treatment in this setting.
|
pRotective vEntilation With Veno-venouS Lung assisT in Respiratory Failure
|
Acute Respiratory Failure With Hypoxia
|
* Device: VV-ECCO2R to enable lower tidal volume mechanical ventilation
|
Inclusion Criteria:~Invasive mechanical ventilation using positive end expiratory pressure (PEEP) ≥ 5cmH2O~Acute and potentially reversible cause of acute respiratory failure as determined by the treating physician~Within 48 hours of the onset of hypoxemia as defined by Pa02/Fi02 less than or equal to 20kPA~Exclusion Criteria:~Age < 16 years old~Intubated and mechanically ventilated via an endotracheal or tracheostomy tube ≥ 7 days (168 hours) up to the time of randomisation~Ability to maintain Vt to ≤ 3ml/kg PBW while maintaining pH ≥ 7.2 as determined by the treating physician~Receiving, or decision to commence, ECMO in the next 24 hours~Mechanical ventilation using high frequency oscillation ventilation or airway pressure release ventilation~Untreated pulmonary embolism, pleural effusion or pneumothorax as the primary cause of acute respiratory failure~Acute respiratory failure fully explained by left ventricular failure or fluid overload (May be determined by clinical assessment or echocardiography/cardiac output monitoring)~Left ventricular failure requiring mechanical support~Contra-indication to limited systemic anticoagulation with heparin~Unable to obtain vascular access to a central vein (internal jugular or femoral vein)~Consent declined~Treatment withdrawal imminent within 24 hours~Patients not expected to survive 90 days on basis of premorbid health status~DNAR (Do Not Attempt Resuscitation) order (excluding advance directives) in place~Severe chronic respiratory disease requiring domiciliary ventilation (except for sleep disordered breathing)~Severe chronic liver disease (Child Pugh >11)~Platelet count < 40,000 mm3 (Prior to catheter insertion)~Previously enrolled in the REST trial~Prisoners
|
16 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality | | 90 days after randomisation |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tidal volume (ml/kg Predicted Body Weight) | | day 2 and day 3 after randomisation |
| Ventilator free days | | 28 days after randomisation |
| Duration of ventilation in survivors | | 28 days after randomisation |
| Need for Extracorporeal Membrane Oxygenation (ECMO) | | 7 days after randomisation |
| Mortality rate | | 28 days, 6 months and 1 year after randomisation |
| Health Related Quality of Life | | 6 months and 1 year after randomisation |
| Adverse Event Rate | | 28 days |
| Health & Social Care Service costs | | 6 months and 1 year after randomisation |
| St George Respiratory Questionnaire | | 1 year after randomisation |
| Need for home oxygen | | 6 months and 1 year after randomisation |
| Post Traumatic Stress Syndrome Questionnaire (PTSS-14) | | 1 year after randomisation |
| Montreal Cognitive Assessment (MoCA-BLIND) or AD8 Dementia Screening Interview (AD8) | | 1 year after randomisation |
|
Extracorporeal, Acute Respiratory Distress Syndrome, Protective Lung Ventilation, Ventilator Induced Lung Injury, Carbon Dioxide Removal, Lung, Lung Injury
|
Respiratory Insufficiency, Hypoxia, Respiration Disorders, Respiratory Tract Diseases, Signs and Symptoms, Respiratory
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Care<br>Standard care with conventional lung protective mechanical ventilation | |
| Experimental: ECCO2R to enable lower tidal volume mechanical ventilation<br>VV-ECCO2R to enable lower tidal volume mechanical ventilation (target tidal volume of ≤ 3ml/kg predicted body weight and a Pplat ≤ 25cmH20) | Device: VV-ECCO2R to enable lower tidal volume mechanical ventilation<br>* In the intervention arm a dual lumen catheter will be inserted into a central vein. VV-ECCO2R is commenced and managed as per study manual. Tidal volumes are then reduced on mechanical ventilation to enable lower tidal volume ventilation. Lower tidal volume facilitated by VV-ECCO2R will continue for a least 2 days up to a maximum of 7 days<br>|
|
pRotective vEntilation With Veno-venouS Lung assisT in Respiratory Failure
Study Overview
=================
Brief Summary
-----------------
This is a trial of a new way of treating patients with respiratory failure. The investigators propose to deliver a multi-centre clinical trial to determine whether veno-venous extracorporeal carbon dioxide removal (VV-ECCO2R) and lower tidal volume mechanical ventilation improves outcomes and is cost-effective, in comparison with standard care in patients who are mechanically ventilated for acute hypoxaemic respiratory failure
Detailed Description
-----------------
Acute hypoxaemic respiratory failure requiring mechanical ventilation is a major cause of morbidity and mortality. A significant proportion of affected patients will have the Acute Respiratory Distress Syndrome (ARDS). Mechanical ventilation is often required to provide adequate gas exchange and although it is life-saving in this setting, it is also now known to contribute to the morbidity and mortality in the condition. Ventilators delivering high pressures and volumes cause regional over distension in the injured lung resulting in further inflammation and non-cardiogenic pulmonary oedema. The release of inflammatory mediators from the damaged lung causes systemic inflammation leading to multi-organ failure and death. The few interventions that have been shown to reduce the high mortality in these patients have targeted ventilator-induced lung injury (VILI). A landmark trial by the ARDSNet trials group found that ventilating patients with acute hypoxaemic respiratory failure secondary to ARDS with a lung protective strategy aiming for a reduced tidal volume of 6ml/kg predicted body weight (PBW) and a maximum end-inspiratory plateau pressure (Pplat) ≤ 30cmH2O decreased mortality from 40% (in the conventional arm treated with tidal volume less than 12ml/kg PBW) to 31%. Extracorporeal carbon dioxide removal (ECCO2R) in association with mechanical ventilation offers a potentially attractive solution to permit tidal volume reduction to less than 6ml/kg PBW and to achieve low plateau pressures (< 25cmH2O). Using these extracorporeal circuits, carbon dioxide can be 'dialysed' out of the blood while the lungs are ventilated in a more protective manner. In recent years, more efficient veno-venous devices have become available. These have replaced arterio-venous devices and have the advantage of not requiring arterial puncture. These can achieve carbon dioxide removal with relatively low extracorporeal blood flows (0.4-1 l/min) requiring only a smaller dual lumen venous catheter. In addition these ECCO2R devices use more biocompatible materials making the device more resistant to clot formation and cause less platelet and clotting factor consumption. Therefore only minimal systemic anticoagulation is required which reduces the likelihood of bleeding complications. These devices are now comparable to renal dialysis equipment, which is routinely used safely as standard care in ICUs in the United Kingdom. Together this highlights the need for a large randomised controlled trial to establish whether VV-ECCO2R in acute hypoxaemic respiratory failure can allow the use of a more protective ventilatory strategy and is associated with improved patient outcomes. Importantly, if there was no benefit, the trial would provide evidence to stop the widespread adoption of an expensive and ineffective or potentially harmful treatment in this setting.
Official Title
-----------------
pRotective vEntilation With Veno-venouS Lung assisT in Respiratory Failure
Conditions
-----------------
Acute Respiratory Failure With Hypoxia
Intervention / Treatment
-----------------
* Device: VV-ECCO2R to enable lower tidal volume mechanical ventilation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Invasive mechanical ventilation using positive end expiratory pressure (PEEP) ≥ 5cmH2O Acute and potentially reversible cause of acute respiratory failure as determined by the treating physician Within 48 hours of the onset of hypoxemia as defined by Pa02/Fi02 less than or equal to 20kPA Exclusion Criteria: Age < 16 years old Intubated and mechanically ventilated via an endotracheal or tracheostomy tube ≥ 7 days (168 hours) up to the time of randomisation Ability to maintain Vt to ≤ 3ml/kg PBW while maintaining pH ≥ 7.2 as determined by the treating physician Receiving, or decision to commence, ECMO in the next 24 hours Mechanical ventilation using high frequency oscillation ventilation or airway pressure release ventilation Untreated pulmonary embolism, pleural effusion or pneumothorax as the primary cause of acute respiratory failure Acute respiratory failure fully explained by left ventricular failure or fluid overload (May be determined by clinical assessment or echocardiography/cardiac output monitoring) Left ventricular failure requiring mechanical support Contra-indication to limited systemic anticoagulation with heparin Unable to obtain vascular access to a central vein (internal jugular or femoral vein) Consent declined Treatment withdrawal imminent within 24 hours Patients not expected to survive 90 days on basis of premorbid health status DNAR (Do Not Attempt Resuscitation) order (excluding advance directives) in place Severe chronic respiratory disease requiring domiciliary ventilation (except for sleep disordered breathing) Severe chronic liver disease (Child Pugh >11) Platelet count < 40,000 mm3 (Prior to catheter insertion) Previously enrolled in the REST trial Prisoners
Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Care<br>Standard care with conventional lung protective mechanical ventilation | |
| Experimental: ECCO2R to enable lower tidal volume mechanical ventilation<br>VV-ECCO2R to enable lower tidal volume mechanical ventilation (target tidal volume of ≤ 3ml/kg predicted body weight and a Pplat ≤ 25cmH20) | Device: VV-ECCO2R to enable lower tidal volume mechanical ventilation<br>* In the intervention arm a dual lumen catheter will be inserted into a central vein. VV-ECCO2R is commenced and managed as per study manual. Tidal volumes are then reduced on mechanical ventilation to enable lower tidal volume ventilation. Lower tidal volume facilitated by VV-ECCO2R will continue for a least 2 days up to a maximum of 7 days<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality | | 90 days after randomisation |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tidal volume (ml/kg Predicted Body Weight) | | day 2 and day 3 after randomisation |
| Ventilator free days | | 28 days after randomisation |
| Duration of ventilation in survivors | | 28 days after randomisation |
| Need for Extracorporeal Membrane Oxygenation (ECMO) | | 7 days after randomisation |
| Mortality rate | | 28 days, 6 months and 1 year after randomisation |
| Health Related Quality of Life | | 6 months and 1 year after randomisation |
| Adverse Event Rate | | 28 days |
| Health & Social Care Service costs | | 6 months and 1 year after randomisation |
| St George Respiratory Questionnaire | | 1 year after randomisation |
| Need for home oxygen | | 6 months and 1 year after randomisation |
| Post Traumatic Stress Syndrome Questionnaire (PTSS-14) | | 1 year after randomisation |
| Montreal Cognitive Assessment (MoCA-BLIND) or AD8 Dementia Screening Interview (AD8) | | 1 year after randomisation |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Extracorporeal, Acute Respiratory Distress Syndrome, Protective Lung Ventilation, Ventilator Induced Lung Injury, Carbon Dioxide Removal, Lung, Lung Injury
|
NCT03876925
|
A Single Arm, Open-label,Phase Ib Study of CT053PTSA in Preciously Treated Patients With Advanced and Metastatic RCC
|
This is a phase Ib,single arm,open label study evaluating the safety and efficacy of CT053PTSA in patients with advanced and metastatic renal cell cancer who have progressed from previous treatment
|
This study is being carried out in two parts,part 1 and part 2. Part 1: This is the dose-escalation part. The primary purpose of the part 1 portion is to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and recommend the appropriate doses of CT053PTSA for further study Part 2: This is the expansion part.The part 2 portion of this study will continue to evaluate the safety and efficacy of CT053PTSA at the appropriate dose recommended in Part 1,in patients with advanced and metastatic RCC
|
A Single Arm, Open-label,Phase Ib Study of CT053PTSA in Preciously Treated Patients With Advanced and Metastatic Renal Cell Cancer
|
Renal Cell Cancer Metastatic
|
* Drug: CT053PTSA
|
Inclusion Criteria:~Histologically or cytologically confirmed renal cell cancer.Patients must be diagnosed with advanced or metastatic disease,disease progressed to previous treatment .~Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)~Toxicity recovered to NCI CTCAE v.4.03 Grade ≤1 from previous treatments (except alopecia)~ECOG performance status (PS) 0 or 1~Life expectancy of ≥ 12 weeks~Adequate organ function~Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol~Exclusion Criteria:~Chemotherapy,radiotherapy,immunotherapy and targeted therapy less than 4 months prior to administration.~Symptomatic, untreated or unstable central nervous system metastases~Uncontrolled hypertension that require anti-hypertensive agents to control, or systolic blood pressure (BP) >140mmHg or diastolic BP >90 mmHg before the first administration (BP is the mean blood pressure of two measures that 1 hours interval or above)~Doppler ultrasound evaluation：Left ventricular ejection fraction < 50%~Significantly clinical arrhythmia or symptomatic bradycardia, or male with QTCF > 450 ms or female with QTCF > 470 ms, or patients with a history of torsion or congenital QT prolonged syndrome long QT syndrome~Certain factors that would preclude adequate absorption of CT053PTSA and gefitinib (eg. unable to swallow, chronic diarrhea, intestinal obstruction)~Patients with evidence of bleeding tendency, including the following cases: gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above; or melena or hematemesis within 2 months; or visceral bleeding that may occur considered by investigator~History of organ transplantation~Any disease of the following bellowed within 12 months prior to administration: Myocardial infarction, severe angina, or unstable angina, coronary or peripheral artery bypass graft, congestive heart failure~Pulmonary embolism or cerebrovascular events (including transient ischemic attack)within 6 months prior to administration~Infection of HIV~Patients with infection of HBV or HCV. Patients with positive of HBsAg or HBcAb,and HBV-DNA can be measured (>500IU/ml). Patients with positive of anti-HCV,and HCV-RNA can be measured by PCR.~Other malignancies within 5 years prior to enrollment, with the exception of carcinoma in situ of the cervix, basal or squamous cell skin cancer~Pregnant or lactating woman~Any other reason the investigator considers the patient is not suitable to participate in the study
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1(dose-escalation part):Maximum Tolerated Dose (MTD) | The maximum tolerated dose (MTD) of the CT053PTSA will be determined according to incidence of dose-limiting toxicity (DLT) assessed by NCI CTCAEv4.03 | Cycle 1 Day 1 to Cycle 1 Day 28 |
| Part 2 (expansion part):Overall Response Rate | Overall response rate (ORR),defined as a partial response (PR) or complete response (CR) occurring at any point post-treatment according to Response Evaluation Criteria in Solid Tumors as assessed by RECIST1.1 | up to approximately 24 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events (AEs) as a measure of safety and tolerability | Safety and tolerability will be assessed through AEs, via monitoring changes in physical examination, clinical laboratory parameters, vital signs and ECGs | up to approximately 24 months |
| Disease Control Rate (DCR) | DCR, proportion of patients with best overall response of CR, PR or SD | up to approximately 24 months |
| Progression-free Survival (PFS) | PFS, defined as time from date of treatment to disease progression or death due to any cause | up to approximately 24 months |
| Duration of Response (DOR) | DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause | up to approximately 24 months |
| Overall Survival (OS) | OS, defined as time from date of treatment to death due to any cause | up to approximately 24 months |
| Maximum observed plasma concentration (Cmax) | to assess the pharmacokinetic profile | Cycle 1 Day1 and Day 28 |
| Time of maximum observed plasma concentration (Tmax) | to assess the pharmacokinetic profile | Cycle 1 Day1 and Day 28 |
| Area under the plasma concentration time curve (AUC) | to assess the pharmacokinetic profile | Cycle 1 Day1 and Day 28 |
|
RCC
|
Carcinoma, Renal Cell, Adenocarcinoma, Carcinoma, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Kidney Neoplasms, Urologic Neoplasms, Urogenital Neoplasms, Neoplasms by Site, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Kidney Diseases, Urologic Diseases, Male Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CT053PTSA<br>60-100mg | Drug: CT053PTSA<br>* Patients will received oral CT053PTSA once daily until disease progression or intolerable toxicity or subject's withdrawal from treatment ,each cycle is defined as 28 days<br>* Other names: Ningetinib;|
|
A Single Arm, Open-label,Phase Ib Study of CT053PTSA in Preciously Treated Patients With Advanced and Metastatic RCC
Study Overview
=================
Brief Summary
-----------------
This is a phase Ib,single arm,open label study evaluating the safety and efficacy of CT053PTSA in patients with advanced and metastatic renal cell cancer who have progressed from previous treatment
Detailed Description
-----------------
This study is being carried out in two parts,part 1 and part 2. Part 1: This is the dose-escalation part. The primary purpose of the part 1 portion is to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD), and recommend the appropriate doses of CT053PTSA for further study Part 2: This is the expansion part.The part 2 portion of this study will continue to evaluate the safety and efficacy of CT053PTSA at the appropriate dose recommended in Part 1,in patients with advanced and metastatic RCC
Official Title
-----------------
A Single Arm, Open-label,Phase Ib Study of CT053PTSA in Preciously Treated Patients With Advanced and Metastatic Renal Cell Cancer
Conditions
-----------------
Renal Cell Cancer Metastatic
Intervention / Treatment
-----------------
* Drug: CT053PTSA
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed renal cell cancer.Patients must be diagnosed with advanced or metastatic disease,disease progressed to previous treatment . Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) Toxicity recovered to NCI CTCAE v.4.03 Grade ≤1 from previous treatments (except alopecia) ECOG performance status (PS) 0 or 1 Life expectancy of ≥ 12 weeks Adequate organ function Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol Exclusion Criteria: Chemotherapy,radiotherapy,immunotherapy and targeted therapy less than 4 months prior to administration. Symptomatic, untreated or unstable central nervous system metastases Uncontrolled hypertension that require anti-hypertensive agents to control, or systolic blood pressure (BP) >140mmHg or diastolic BP >90 mmHg before the first administration (BP is the mean blood pressure of two measures that 1 hours interval or above) Doppler ultrasound evaluation：Left ventricular ejection fraction < 50% Significantly clinical arrhythmia or symptomatic bradycardia, or male with QTCF > 450 ms or female with QTCF > 470 ms, or patients with a history of torsion or congenital QT prolonged syndrome long QT syndrome Certain factors that would preclude adequate absorption of CT053PTSA and gefitinib (eg. unable to swallow, chronic diarrhea, intestinal obstruction) Patients with evidence of bleeding tendency, including the following cases: gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occult blood ++ and above; or melena or hematemesis within 2 months; or visceral bleeding that may occur considered by investigator History of organ transplantation Any disease of the following bellowed within 12 months prior to administration: Myocardial infarction, severe angina, or unstable angina, coronary or peripheral artery bypass graft, congestive heart failure Pulmonary embolism or cerebrovascular events (including transient ischemic attack)within 6 months prior to administration Infection of HIV Patients with infection of HBV or HCV. Patients with positive of HBsAg or HBcAb,and HBV-DNA can be measured (>500IU/ml). Patients with positive of anti-HCV,and HCV-RNA can be measured by PCR. Other malignancies within 5 years prior to enrollment, with the exception of carcinoma in situ of the cervix, basal or squamous cell skin cancer Pregnant or lactating woman Any other reason the investigator considers the patient is not suitable to participate in the study
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CT053PTSA<br>60-100mg | Drug: CT053PTSA<br>* Patients will received oral CT053PTSA once daily until disease progression or intolerable toxicity or subject's withdrawal from treatment ,each cycle is defined as 28 days<br>* Other names: Ningetinib;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1(dose-escalation part):Maximum Tolerated Dose (MTD) | The maximum tolerated dose (MTD) of the CT053PTSA will be determined according to incidence of dose-limiting toxicity (DLT) assessed by NCI CTCAEv4.03 | Cycle 1 Day 1 to Cycle 1 Day 28 |
| Part 2 (expansion part):Overall Response Rate | Overall response rate (ORR),defined as a partial response (PR) or complete response (CR) occurring at any point post-treatment according to Response Evaluation Criteria in Solid Tumors as assessed by RECIST1.1 | up to approximately 24 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events (AEs) as a measure of safety and tolerability | Safety and tolerability will be assessed through AEs, via monitoring changes in physical examination, clinical laboratory parameters, vital signs and ECGs | up to approximately 24 months |
| Disease Control Rate (DCR) | DCR, proportion of patients with best overall response of CR, PR or SD | up to approximately 24 months |
| Progression-free Survival (PFS) | PFS, defined as time from date of treatment to disease progression or death due to any cause | up to approximately 24 months |
| Duration of Response (DOR) | DOR, defined as time from the first documented CR or PR to first documented progression or death due to any cause | up to approximately 24 months |
| Overall Survival (OS) | OS, defined as time from date of treatment to death due to any cause | up to approximately 24 months |
| Maximum observed plasma concentration (Cmax) | to assess the pharmacokinetic profile | Cycle 1 Day1 and Day 28 |
| Time of maximum observed plasma concentration (Tmax) | to assess the pharmacokinetic profile | Cycle 1 Day1 and Day 28 |
| Area under the plasma concentration time curve (AUC) | to assess the pharmacokinetic profile | Cycle 1 Day1 and Day 28 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RCC
|
NCT05271799
|
A Study to Evaluate Pharmacokinetic, Safety, Tolerability and Relative Bioavailability of Gepotidacin in Healthy Adult Male and Female Participants
|
This study is a randomized, open-label, two periods, cross-over pharmacokinetic, safety, tolerability and relative bioavailability of gepotidacin in healthy adult male and female participants of aged 18 to 50 years.
|
A Randomized, Open-Label, Single-Dose, 2-Period, Crossover Study to Compare Gepotidacin Powder for Oral Suspension With the Adult Tablet Formulation in Healthy Male and Female Participants Aged 18 to 50 Years
|
Healthy Volunteers
|
* Drug: Gepotidacin
|
Inclusion Criteria:~Participant must be 18 to 50 years of age, inclusive, at the time of signing the informed consent.~Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, clinical laboratory tests, vital sign measurements, and 12-lead electrocardiogram results. A participant with a clinical abnormality or laboratory parameters outside the reference range may be included only if the investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.~Body weight more than or equal to (>=) 50.0 kilograms (kg) (110 pound) for males and >=45 kg (99 pound) for females and body mass index within the range 18.5 to 32.0 kilogram per square meters (kg/m^2) (inclusive).~Male or Female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male participants: Male participants are eligible to participate if they agree to the following during the study intervention period until completion of the follow-up visit: Refrain from donating sperm PLUS, either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below: Agree to use a male condom with female partner and should also be advised of the benefit for a female partner to use a highly effective method of contraception, as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person. b. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is not a WOCBP OR Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of less than (<) 1 percent (%), for at least 30 days prior to dosing until completion of the follow up visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.~Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.~Exclusion Criteria:~History or presence of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, constituting a risk when taking the study intervention, or interfering with the interpretation of data.~Abnormal blood pressure as determined by the investigator or designee~Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention, or any other condition that may place the participant at risk, in the opinion of the investigator.~Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening.~Use of any systemic antibiotic within 30 days of screening.~Within 2 months before screening, either a confirmed history of Clostridium difficile diarrhea infection or a past positive of Clostridium difficile toxin test.~Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert syndrome or asymptomatic gallstones).~History of drug and/or alcohol abuse within 6 months before screening, as determined by the investigator, or has a positive drug screen at screening or upon admission to the clinic.~History of sensitivity/hypersensitivity to any of the study drugs, components thereof, or a history of drug or other allergy that, in the opinion of the investigator or the GlaxoSmithKline medical monitor contraindicates their participation.~History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinic uses heparin to maintain intravenous cannula patency).~Impaired sense of taste or smell, in the opinion of the investigator.~Participants must abstain from taking prescription or non-prescription drugs (except for hormonal contraceptives and/or acetaminophen [up to 2 grams per day]), vitamins, and dietary or herbal supplements, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to study intervention until completion of the follow-up visit, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.~Participants must abstain from taking QT-prolonging drugs or drugs known to increase the risk of torsades de pointes or the participant is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor within 7 days or 5 half-lives (whichever is longer).~Previous exposure to gepotidacin within 12 months prior to starting study intervention~Participant has participated in a clinical trial and has received an investigational product prior to gepotidacin administration within 30 days, 5 half-lives, or twice the duration of the biological effect of investigational product (whichever is longer).~Participant has participated in a clinical trial with frequent blood sampling and/or sampling blood volumes that in total may reached an extracted blood volume above 7 milliliter per kilogram (mL/kg) (i.e., approximately 500 milliliter (mL) for a 70 kg participant) within the previous 56 days prior to informed consent.~Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention.~Alanine aminotransferase (ALT) more than (>)1.5 * upper limit of normal (ULN) at screening or check-in.~Bilirubin >1.5 * ULN (isolated bilirubin >1.5 * ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening or check-in.~History of any kidney disease or current or chronic history of impaired renal function as indicated by an estimated creatinine clearance <60 milliliter per minute (mL/min).~A positive test for human immunodeficiency virus antibody.~History of regular alcohol consumption within 6 months of screening defined as an average weekly intake of >21 units (or an average daily intake of >3 units) for males or an average weekly intake of >14 units (or an average daily intake >2 units) for females. One unit is equivalent to 270 mL of full-strength beer, 470 mL of light beer, 30 mL of spirits, or 100 mL of wine.~Urinary cotinine level indicative of smoking or history of regular use of tobacco- or nicotine-containing products within 3 months of screening.~Clinically significant abnormal findings in serum chemistry, hematology, or urinalysis results obtained at screening or check-in (Day-1).~Baseline QTcF of >450 milliseconds (msec) at screening or check-in (Day-1).
|
18 Years
|
50 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a two periods, crossover study
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Periods 1 and 2: Area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: AUC from time zero to the time of the last quantifiable concentration (AUC[0-t]) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Maximum observed plasma concentration (Cmax) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Periods 1 and 2: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | | Up to 14 days |
| Periods 1 and 2: Maximum change from Baseline in QT interval corrected with Fridericia's method (QTcF) | | Baseline and up to 14 days |
| Periods 1 and 2: Time to reach maximum observed plasma concentration (Tmax) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin. | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Absorption lag time (Tlag) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Terminal phase half-life (t1/2) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Apparent volume of distribution (Vz/F) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Relative bioavailability (Frel) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Apparent oral clearance (CL/F) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: AUC from time zero to 24 hours (AUC[0-24]) of gepotidacin | Urine samples will be collected for the concentrations of gepotidacin. | Up to 24 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Total unchanged drug (Ae total) of gepotidacin | Urine samples will be collected for the concentrations of gepotidacin. | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Percentage of the given dose of drug excreted in urine (fe%) of gepotidacin | Urine samples will be collected for the concentrations of gepotidacin. | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Renal clearance of drug (CLr) of gepotidacin | Urine samples will be collected for the concentrations of gepotidacin. | Up to 48 hours post dose in each period (each period is 3 days) |
|
Gepotidacin, Relative Bioavailability, Healthy participants
|
Gepotidacin, Topoisomerase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving gepotidacin powder for oral suspension followed by tablet<br> | Drug: Gepotidacin<br>* Gepotidacin will be administered<br>|
| Experimental: Participants receiving gepotidacin tablet followed by powder for oral suspension<br> | Drug: Gepotidacin<br>* Gepotidacin will be administered<br>|
|
A Study to Evaluate Pharmacokinetic, Safety, Tolerability and Relative Bioavailability of Gepotidacin in Healthy Adult Male and Female Participants
Study Overview
=================
Brief Summary
-----------------
This study is a randomized, open-label, two periods, cross-over pharmacokinetic, safety, tolerability and relative bioavailability of gepotidacin in healthy adult male and female participants of aged 18 to 50 years.
Official Title
-----------------
A Randomized, Open-Label, Single-Dose, 2-Period, Crossover Study to Compare Gepotidacin Powder for Oral Suspension With the Adult Tablet Formulation in Healthy Male and Female Participants Aged 18 to 50 Years
Conditions
-----------------
Healthy Volunteers
Intervention / Treatment
-----------------
* Drug: Gepotidacin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant must be 18 to 50 years of age, inclusive, at the time of signing the informed consent. Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, clinical laboratory tests, vital sign measurements, and 12-lead electrocardiogram results. A participant with a clinical abnormality or laboratory parameters outside the reference range may be included only if the investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Body weight more than or equal to (>=) 50.0 kilograms (kg) (110 pound) for males and >=45 kg (99 pound) for females and body mass index within the range 18.5 to 32.0 kilogram per square meters (kg/m^2) (inclusive). Male or Female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male participants: Male participants are eligible to participate if they agree to the following during the study intervention period until completion of the follow-up visit: Refrain from donating sperm PLUS, either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below: Agree to use a male condom with female partner and should also be advised of the benefit for a female partner to use a highly effective method of contraception, as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person. b. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is not a WOCBP OR Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of less than (<) 1 percent (%), for at least 30 days prior to dosing until completion of the follow up visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol. Exclusion Criteria: History or presence of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, constituting a risk when taking the study intervention, or interfering with the interpretation of data. Abnormal blood pressure as determined by the investigator or designee Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention, or any other condition that may place the participant at risk, in the opinion of the investigator. Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening. Use of any systemic antibiotic within 30 days of screening. Within 2 months before screening, either a confirmed history of Clostridium difficile diarrhea infection or a past positive of Clostridium difficile toxin test. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert syndrome or asymptomatic gallstones). History of drug and/or alcohol abuse within 6 months before screening, as determined by the investigator, or has a positive drug screen at screening or upon admission to the clinic. History of sensitivity/hypersensitivity to any of the study drugs, components thereof, or a history of drug or other allergy that, in the opinion of the investigator or the GlaxoSmithKline medical monitor contraindicates their participation. History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinic uses heparin to maintain intravenous cannula patency). Impaired sense of taste or smell, in the opinion of the investigator. Participants must abstain from taking prescription or non-prescription drugs (except for hormonal contraceptives and/or acetaminophen [up to 2 grams per day]), vitamins, and dietary or herbal supplements, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to study intervention until completion of the follow-up visit, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study. Participants must abstain from taking QT-prolonging drugs or drugs known to increase the risk of torsades de pointes or the participant is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor within 7 days or 5 half-lives (whichever is longer). Previous exposure to gepotidacin within 12 months prior to starting study intervention Participant has participated in a clinical trial and has received an investigational product prior to gepotidacin administration within 30 days, 5 half-lives, or twice the duration of the biological effect of investigational product (whichever is longer). Participant has participated in a clinical trial with frequent blood sampling and/or sampling blood volumes that in total may reached an extracted blood volume above 7 milliliter per kilogram (mL/kg) (i.e., approximately 500 milliliter (mL) for a 70 kg participant) within the previous 56 days prior to informed consent. Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention. Alanine aminotransferase (ALT) more than (>)1.5 * upper limit of normal (ULN) at screening or check-in. Bilirubin >1.5 * ULN (isolated bilirubin >1.5 * ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening or check-in. History of any kidney disease or current or chronic history of impaired renal function as indicated by an estimated creatinine clearance <60 milliliter per minute (mL/min). A positive test for human immunodeficiency virus antibody. History of regular alcohol consumption within 6 months of screening defined as an average weekly intake of >21 units (or an average daily intake of >3 units) for males or an average weekly intake of >14 units (or an average daily intake >2 units) for females. One unit is equivalent to 270 mL of full-strength beer, 470 mL of light beer, 30 mL of spirits, or 100 mL of wine. Urinary cotinine level indicative of smoking or history of regular use of tobacco- or nicotine-containing products within 3 months of screening. Clinically significant abnormal findings in serum chemistry, hematology, or urinalysis results obtained at screening or check-in (Day-1). Baseline QTcF of >450 milliseconds (msec) at screening or check-in (Day-1).
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a two periods, crossover study
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving gepotidacin powder for oral suspension followed by tablet<br> | Drug: Gepotidacin<br>* Gepotidacin will be administered<br>|
| Experimental: Participants receiving gepotidacin tablet followed by powder for oral suspension<br> | Drug: Gepotidacin<br>* Gepotidacin will be administered<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Periods 1 and 2: Area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: AUC from time zero to the time of the last quantifiable concentration (AUC[0-t]) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Maximum observed plasma concentration (Cmax) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Periods 1 and 2: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | | Up to 14 days |
| Periods 1 and 2: Maximum change from Baseline in QT interval corrected with Fridericia's method (QTcF) | | Baseline and up to 14 days |
| Periods 1 and 2: Time to reach maximum observed plasma concentration (Tmax) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin. | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Absorption lag time (Tlag) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Terminal phase half-life (t1/2) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Apparent volume of distribution (Vz/F) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Relative bioavailability (Frel) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Apparent oral clearance (CL/F) of gepotidacin | Blood samples will be collected for the concentrations of gepotidacin | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: AUC from time zero to 24 hours (AUC[0-24]) of gepotidacin | Urine samples will be collected for the concentrations of gepotidacin. | Up to 24 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Total unchanged drug (Ae total) of gepotidacin | Urine samples will be collected for the concentrations of gepotidacin. | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Percentage of the given dose of drug excreted in urine (fe%) of gepotidacin | Urine samples will be collected for the concentrations of gepotidacin. | Up to 48 hours post dose in each period (each period is 3 days) |
| Periods 1 and 2: Renal clearance of drug (CLr) of gepotidacin | Urine samples will be collected for the concentrations of gepotidacin. | Up to 48 hours post dose in each period (each period is 3 days) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gepotidacin, Relative Bioavailability, Healthy participants
|
|
NCT00444821
|
The (PIVOTAL) Study
|
The purpose of this study is to compare endovascular repair using any FDA approved Medtronic AAA Stent Graft System versus surveillance in subjects with smaller abdominal aortic aneurysms (AAA)(4-5CM), with respect to AAA rupture and AAA related deaths.
|
Positive Impact of Endovascular Options for Treating Aneurysms Early (PIVOTAL)
|
ABDOMINAL AORTIC ANEURYSMS
|
* Device: AneuRx AAA stent graft / Talent AAA stent graft
|
Inclusion Criteria:~40 to 90 years of age~Meet all indications for use as stated in the Medtronic Vascular AAA Endograft Instructions for Use~Maximum aneurysm diameter of 4-5cm~If female patient with child bearing potential, must have a documented negative pregnancy test within seven(7)days prior to inclusion~Patient is willing and able to comply with the specified follow-up evaluation~Life expectancy at least 3 years~Exclusion Criteria:~Meet any of the Contraindications stated in the Medtronic Vascular AAA Endograft instructions for Use~Known co-existing condition with a life expectancy of less than 3 years~Major surgical or interventional procedure (vascular and/or non-vascular)within 30 days prior to study enrollment~Subjects enrolled in another clinical trial or anticipated to be included into a trial, which may interfere with this study, or subjects already enrolled in this trial before.~Planned conduit procedure for introduction of endograft
|
40 Years
|
90 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects That Experienced Rupture or Aneurysm Related Death | | 3 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aneurysm Growth >0.5 cm | After repair, AAA enlargement by >0.5cm | 1 year |
| Secondary Endovascular Procedures Between the 30-day Post Treatment and 3-year Follow-up | secondary interventions in those that had successful delivery and deployment by treatment group randomized to. | study termination |
|
AAA, Aneurysm, AneuRx, Talent
|
Aneurysm, Aortic Aneurysm, Aortic Aneurysm, Abdominal, Vascular Diseases, Cardiovascular Diseases, Aortic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Surveillance<br> | |
| Experimental: Early Endovascular Repair<br> | Device: AneuRx AAA stent graft / Talent AAA stent graft<br>* Catheter based stent graft inserted to seal off an abdominal aortic aneurysm<br>|
|
The (PIVOTAL) Study
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare endovascular repair using any FDA approved Medtronic AAA Stent Graft System versus surveillance in subjects with smaller abdominal aortic aneurysms (AAA)(4-5CM), with respect to AAA rupture and AAA related deaths.
Official Title
-----------------
Positive Impact of Endovascular Options for Treating Aneurysms Early (PIVOTAL)
Conditions
-----------------
ABDOMINAL AORTIC ANEURYSMS
Intervention / Treatment
-----------------
* Device: AneuRx AAA stent graft / Talent AAA stent graft
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 40 to 90 years of age Meet all indications for use as stated in the Medtronic Vascular AAA Endograft Instructions for Use Maximum aneurysm diameter of 4-5cm If female patient with child bearing potential, must have a documented negative pregnancy test within seven(7)days prior to inclusion Patient is willing and able to comply with the specified follow-up evaluation Life expectancy at least 3 years Exclusion Criteria: Meet any of the Contraindications stated in the Medtronic Vascular AAA Endograft instructions for Use Known co-existing condition with a life expectancy of less than 3 years Major surgical or interventional procedure (vascular and/or non-vascular)within 30 days prior to study enrollment Subjects enrolled in another clinical trial or anticipated to be included into a trial, which may interfere with this study, or subjects already enrolled in this trial before. Planned conduit procedure for introduction of endograft
Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 90 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Surveillance<br> | |
| Experimental: Early Endovascular Repair<br> | Device: AneuRx AAA stent graft / Talent AAA stent graft<br>* Catheter based stent graft inserted to seal off an abdominal aortic aneurysm<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects That Experienced Rupture or Aneurysm Related Death | | 3 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aneurysm Growth >0.5 cm | After repair, AAA enlargement by >0.5cm | 1 year |
| Secondary Endovascular Procedures Between the 30-day Post Treatment and 3-year Follow-up | secondary interventions in those that had successful delivery and deployment by treatment group randomized to. | study termination |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AAA, Aneurysm, AneuRx, Talent
|
|
NCT04203680
|
Histidine-Tryptophan-Ketoglutarate Solution Versus Blood Cardioplegia in CABG
|
Background: In cardiac surgery, myocardial protection is mandatory during cross clamp time followed by reperfusion. Use of cardioplegic solutions preserves myocardial energy stores, hindering electrolyte disturbances and acidosis during periods of myocardial ischemia. This study was designed to compare the efficacy and safety of Histidine-tryptophan-ketoglutarate (HTK) solution versus blood cardioplegia in coronary artery bypass graft surgery.~Methods: Three hundred and twenty patients were randomized into Histidine-tryptophan-ketoglutarate (HTK) group and blood cardioplegia group. Ventilation time, total bypass time, cross clamp time, length of ICU or hospital stay and the early postoperative outcomes were analysed.
|
The Ethics Committee of Ain Shams university approved this randomized prospective double-blinded controlled parallel group study to be held in Cardiothoracic Academy for three months from December 2019 to April 2020. The study was conducted on three hundred and twenty older patients aged from 60-80 years old posted for elective coronary artery bypass grafting (CABG). Written informed consents were signed by all patients. Exclusion criteria included (1) patients with Unstable angina (class III or IV); (2) Poor left ventricular function (LVEF <40%) ;(3) Patient with acute myocardial infarction; (4) Previous CABG; (5) Previous renal failure; (6) Preoperative Aortic valve or Mitral valve disease requiring replacement ;(7) Urgent CABG operation.~A detailed medical history, including medications used, symptoms and risk factors for ischemic heart disease (smoking, DM, hypertension), NYHA classification and full investigations were assessed on the night of the surgical procedure. Anesthesia management was standardized for all patients. Premedication with midazolam was limited to a maximum of 0.05 mg/kg. Anesthesia was done with 12 μg/kg fentanyl, 5-7 mg/kg thiopental sodium, and 0.15 mg/kg pancuronium and was maintained with 1-2.0% isoflurane. Heart rate and blood pressure were maintained within 20% of the baseline values. Anticoagulation was achieved with heparin 300 U/kg administered into the right atrium to maintain an activated clotting time above 480 s. Cardiopulmonary bypass (CPB) was established by non-occlusive roller pumps, membrane oxygenators and arterial line filtration. The CPB circuit was primed with 1.8 l lactated Ringer's solution and 50 ml of 20% mannitol. Management of CPB included systemic hypothermia during aortic cross-clamping, targeted mean perfusion pressure between 60 and 80 mmHg, and pump flow rates of 2.2 l/min/m2.Intraoperatively the patients were monitored using ECG, pulse oximetry, Invasive blood pressure monitoring, arterial blood gases, central venous line catheter and temperature probe. Surgical approach was performed by median sternotomy.~Patients were randomly allocated into 2 groups either HTK group and blood cardioplegia group according to a computer-generated randomization code, with allocation ratio 1:1. Opaque sealed envelopes were prepared according to the randomization schedule, and were opened by a clinician not involved in any part of the study.~In the HTK group, patients received 30 ml/kg of HTK cardioplegic solution at 4°C through an antegrade fashion at an initial perfusion pressure of 80-100 mmHg. In blood cardioplegia group, patients received one liter of blood cardioplegia was given with the antegrade route at 30°C, or lower. Blood maintenance cardioplegia was repeated every 30-45mins. The study medications were calculated and prepared by ICU residents who were not a part of the research team. To ensure blinding of study drug administration, the medication vials were kept in opaque bags. Trial bags were blinded and marked with a unique number. The allocation of trial drugs was determined by the web-based randomization system by the allocation of the bag number. The end-point assessor of the outcomes was blinded to the study drugs.~Before separation from CPB, patients were rewarmed to 36-37°C. After separation from CPB, heparin was neutralized with protamine sulfate 1 mg/100 U heparin to reach an activated clotting time within 10% of baseline. All patients were then transferred to the ICU after surgery.~The primary end-point of the study included early postoperative outcomes including cardiac enzymes preoperatively, 8 & 24 hour post-operatively, 30-day mortality, wall motion abnormalities and pericardial effusion. The secondary end-points included ventilation time, cross clamp and total bypass time, length of ICU stay, length of hospital stay, need for inotropic support, 30-day readmission, the incidence of late postoperative complications as renal dysfunction.
|
Efficacy of Histidine-Tryptophan-Ketoglutarate Solution Versus Blood Cardioplegia in Coronary Artery Bypass Graft Surgery: A Randomized Double Blinded Study
|
Cardioplegia Solution Adverse Reaction
|
* Drug: HTK cardioplegic solution
* Drug: blood cardioplegia
|
Inclusion Criteria:~age from 60-80 years old~elective CABG~no comorbidities~Exclusion Criteria:~patients with Unstable angina~Poor left ventricular function~Patient with acute myocardial infarction~previous renal failure~Preoperative Aortic valve or Mitral valve disease requiring replacement
|
60 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality rate | mortality rate | up to 30 days postoperative |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Troponin I level | level of troponin in the blood | Up to 24 hours postoperative |
| length of ICU stay | ICU stay duration | up to 3 days postoperative |
| length of hospital stay | hospital stay duration | up to 7 days postoperative |
|
Cardioplegic Solutions, Tryptophan, Pharmaceutical Solutions, Antidepressive Agents, Second-Generation, Antidepressive Agents, Psychotropic Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: HTK group<br>Patients received 30 ml/kg of HTK cardioplegic solution at 4°C through an antegrade fashion at an initial perfusion pressure of 80-100 mmHg | Drug: HTK cardioplegic solution<br>* 30 ml/kg of HTK cardioplegic solution at 4°C through an antegrade fashion at an initial perfusion pressure of 80-100 mmHg<br>* Other names: Histidine-tryptophan-ketoglutarate solution;|
| Active Comparator: blood cardioplegia group<br>patients received one liter of blood cardioplegia was given with the antegrade route at 30°C, or lower. Blood maintenance cardioplegia was repeated every 30-45mins | Drug: blood cardioplegia<br>* one liter of blood cardioplegia was given with the antegrade route at 30°C, or lower. Blood maintenance cardioplegia was repeated every 30-45mins<br>|
|
Histidine-Tryptophan-Ketoglutarate Solution Versus Blood Cardioplegia in CABG
Study Overview
=================
Brief Summary
-----------------
Background: In cardiac surgery, myocardial protection is mandatory during cross clamp time followed by reperfusion. Use of cardioplegic solutions preserves myocardial energy stores, hindering electrolyte disturbances and acidosis during periods of myocardial ischemia. This study was designed to compare the efficacy and safety of Histidine-tryptophan-ketoglutarate (HTK) solution versus blood cardioplegia in coronary artery bypass graft surgery. Methods: Three hundred and twenty patients were randomized into Histidine-tryptophan-ketoglutarate (HTK) group and blood cardioplegia group. Ventilation time, total bypass time, cross clamp time, length of ICU or hospital stay and the early postoperative outcomes were analysed.
Detailed Description
-----------------
The Ethics Committee of Ain Shams university approved this randomized prospective double-blinded controlled parallel group study to be held in Cardiothoracic Academy for three months from December 2019 to April 2020. The study was conducted on three hundred and twenty older patients aged from 60-80 years old posted for elective coronary artery bypass grafting (CABG). Written informed consents were signed by all patients. Exclusion criteria included (1) patients with Unstable angina (class III or IV); (2) Poor left ventricular function (LVEF <40%) ;(3) Patient with acute myocardial infarction; (4) Previous CABG; (5) Previous renal failure; (6) Preoperative Aortic valve or Mitral valve disease requiring replacement ;(7) Urgent CABG operation. A detailed medical history, including medications used, symptoms and risk factors for ischemic heart disease (smoking, DM, hypertension), NYHA classification and full investigations were assessed on the night of the surgical procedure. Anesthesia management was standardized for all patients. Premedication with midazolam was limited to a maximum of 0.05 mg/kg. Anesthesia was done with 12 μg/kg fentanyl, 5-7 mg/kg thiopental sodium, and 0.15 mg/kg pancuronium and was maintained with 1-2.0% isoflurane. Heart rate and blood pressure were maintained within 20% of the baseline values. Anticoagulation was achieved with heparin 300 U/kg administered into the right atrium to maintain an activated clotting time above 480 s. Cardiopulmonary bypass (CPB) was established by non-occlusive roller pumps, membrane oxygenators and arterial line filtration. The CPB circuit was primed with 1.8 l lactated Ringer's solution and 50 ml of 20% mannitol. Management of CPB included systemic hypothermia during aortic cross-clamping, targeted mean perfusion pressure between 60 and 80 mmHg, and pump flow rates of 2.2 l/min/m2.Intraoperatively the patients were monitored using ECG, pulse oximetry, Invasive blood pressure monitoring, arterial blood gases, central venous line catheter and temperature probe. Surgical approach was performed by median sternotomy. Patients were randomly allocated into 2 groups either HTK group and blood cardioplegia group according to a computer-generated randomization code, with allocation ratio 1:1. Opaque sealed envelopes were prepared according to the randomization schedule, and were opened by a clinician not involved in any part of the study. In the HTK group, patients received 30 ml/kg of HTK cardioplegic solution at 4°C through an antegrade fashion at an initial perfusion pressure of 80-100 mmHg. In blood cardioplegia group, patients received one liter of blood cardioplegia was given with the antegrade route at 30°C, or lower. Blood maintenance cardioplegia was repeated every 30-45mins. The study medications were calculated and prepared by ICU residents who were not a part of the research team. To ensure blinding of study drug administration, the medication vials were kept in opaque bags. Trial bags were blinded and marked with a unique number. The allocation of trial drugs was determined by the web-based randomization system by the allocation of the bag number. The end-point assessor of the outcomes was blinded to the study drugs. Before separation from CPB, patients were rewarmed to 36-37°C. After separation from CPB, heparin was neutralized with protamine sulfate 1 mg/100 U heparin to reach an activated clotting time within 10% of baseline. All patients were then transferred to the ICU after surgery. The primary end-point of the study included early postoperative outcomes including cardiac enzymes preoperatively, 8 & 24 hour post-operatively, 30-day mortality, wall motion abnormalities and pericardial effusion. The secondary end-points included ventilation time, cross clamp and total bypass time, length of ICU stay, length of hospital stay, need for inotropic support, 30-day readmission, the incidence of late postoperative complications as renal dysfunction.
Official Title
-----------------
Efficacy of Histidine-Tryptophan-Ketoglutarate Solution Versus Blood Cardioplegia in Coronary Artery Bypass Graft Surgery: A Randomized Double Blinded Study
Conditions
-----------------
Cardioplegia Solution Adverse Reaction
Intervention / Treatment
-----------------
* Drug: HTK cardioplegic solution
* Drug: blood cardioplegia
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age from 60-80 years old elective CABG no comorbidities Exclusion Criteria: patients with Unstable angina Poor left ventricular function Patient with acute myocardial infarction previous renal failure Preoperative Aortic valve or Mitral valve disease requiring replacement
Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: HTK group<br>Patients received 30 ml/kg of HTK cardioplegic solution at 4°C through an antegrade fashion at an initial perfusion pressure of 80-100 mmHg | Drug: HTK cardioplegic solution<br>* 30 ml/kg of HTK cardioplegic solution at 4°C through an antegrade fashion at an initial perfusion pressure of 80-100 mmHg<br>* Other names: Histidine-tryptophan-ketoglutarate solution;|
| Active Comparator: blood cardioplegia group<br>patients received one liter of blood cardioplegia was given with the antegrade route at 30°C, or lower. Blood maintenance cardioplegia was repeated every 30-45mins | Drug: blood cardioplegia<br>* one liter of blood cardioplegia was given with the antegrade route at 30°C, or lower. Blood maintenance cardioplegia was repeated every 30-45mins<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality rate | mortality rate | up to 30 days postoperative |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Troponin I level | level of troponin in the blood | Up to 24 hours postoperative |
| length of ICU stay | ICU stay duration | up to 3 days postoperative |
| length of hospital stay | hospital stay duration | up to 7 days postoperative |
|
|
NCT00036582
|
Clozapine vs. Placebo in Treatment-Refractory Bipolar Disorder in Children and Adolescents
|
The purpose of this study is to determine the safety and effectiveness of clozapine in children and adolescents with treatment resistant bipolar disorder. This study will also explore how the brain functions in early-onset bipolar disorder.
|
Bipolar disorder (BPD) in children and adolescents is a serious illness that carries a high risk for chronicity, impairing comorbidities, and completed suicide. Treatment options are often limited by inefficacy or intolerable side effects. Open trials in adult bipolar subjects and several case series in children and adolescents provide preliminary evidence that clozapine, an atypical antipsychotic, may be effective in treatment-resistant bipolar disorder. The first specific aim of this study is to test the efficacy and safety of clozapine compared to placebo in a double-blind study of children and adolescents with treatment refractory BPD. Other specific aims involve exploring the pathophysiology of early-onset BPD by 1) testing the hypotheses that, compared to controls, children with BPD have increased psychophysiological reactivity to emotional stimuli and decreased prepulse inhibition; 2) obtaining samples of genetic material from affected probands and their parents for later analysis; and 3) identifying anatomic changes in the brains of children with BPD using structural MRI.
|
Clozapine vs Placebo In Treatment-Refractory Bipolar Disorder In Children And Adolescents
|
Bipolar Disorder
|
* Drug: Clozapine
|
INCLUSION CRITERIA (All 5 must be met): Children with BPD~Ages 8-17~Currently meets criteria for bipolar disorder, manic or mixed, as determined by the K-SADS diagnostic interview.~Treatment-resistant, defined as a history of unsuccessful trials of lithium (documented level of greater than 0.8 mEq/L), valproic acid (documented level of greater than 50 ug/ml), carbamazepine (documented level greater than or equal to 6 ug/ml), a neuroleptic as well as a combination of two of these agents. Each trial must have been at least 6 weeks long. A trial will be considered unsuccessful if the medication was discontinued because of intolerable side-effects.~The child should be in treatment with a community psychiatrist to whom they will return upon completion of the study.~Current CGAS score less than 50~EXCLUSION CRITERIA: Children with BPD~Full scale IQ less than 80~Meets criteria for substance use disorder in the three months prior to randomization~Currently pregnant, lactating, or sexually active without using a barrier method of contraception~Previous treatment with clozapine~History of seizures~History of leukopenia or agranulocytosis~Presence of an unstable medical illness~INCLUSION CRITERIA: CONTROLS~Control subjects will be age- and sex- matched to the BPD subjects. They will have normal physical and neurological examinations, and an identified primary care physician. Both control subjects and their first-degree relatives must be free of current or past psychopathology.~EXCLUSION CRITERIA: CONTROLS~I.Q less than 80; ongoing medical illness; neurologic disorder (including seizures); pregnancy; meeting past or present criteria for any diagnosis on the K-SADS-PL; meeting criterion A of post-traumatic stress disorder (exposure to a traumatic event).
| null | null |
All
|
No
|
Primary Purpose: Treatment
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
HV, Psychophysiology, Structural MRI, Genetics, Bipolar Disorder, Children and Adolescents, Clozapine, Placebo, Treatment-Refractory, Bipolar, Healthy Volunteer, BPD, Normal Control
|
Clozapine, Serotonin Antagonists, Serotonin Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs, Antipsychotic Agents, Tranquilizing Agents, Central Nervous System Depressants, Psychotropic Drugs, GABA Antagonists, GABA Agents
|
| Intervention/Treatment |
| --- |
|Drug: Clozapine|nan|
|
Clozapine vs. Placebo in Treatment-Refractory Bipolar Disorder in Children and Adolescents
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the safety and effectiveness of clozapine in children and adolescents with treatment resistant bipolar disorder. This study will also explore how the brain functions in early-onset bipolar disorder.
Detailed Description
-----------------
Bipolar disorder (BPD) in children and adolescents is a serious illness that carries a high risk for chronicity, impairing comorbidities, and completed suicide. Treatment options are often limited by inefficacy or intolerable side effects. Open trials in adult bipolar subjects and several case series in children and adolescents provide preliminary evidence that clozapine, an atypical antipsychotic, may be effective in treatment-resistant bipolar disorder. The first specific aim of this study is to test the efficacy and safety of clozapine compared to placebo in a double-blind study of children and adolescents with treatment refractory BPD. Other specific aims involve exploring the pathophysiology of early-onset BPD by 1) testing the hypotheses that, compared to controls, children with BPD have increased psychophysiological reactivity to emotional stimuli and decreased prepulse inhibition; 2) obtaining samples of genetic material from affected probands and their parents for later analysis; and 3) identifying anatomic changes in the brains of children with BPD using structural MRI.
Official Title
-----------------
Clozapine vs Placebo In Treatment-Refractory Bipolar Disorder In Children And Adolescents
Conditions
-----------------
Bipolar Disorder
Intervention / Treatment
-----------------
* Drug: Clozapine
Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA (All 5 must be met): Children with BPD Ages 8-17 Currently meets criteria for bipolar disorder, manic or mixed, as determined by the K-SADS diagnostic interview. Treatment-resistant, defined as a history of unsuccessful trials of lithium (documented level of greater than 0.8 mEq/L), valproic acid (documented level of greater than 50 ug/ml), carbamazepine (documented level greater than or equal to 6 ug/ml), a neuroleptic as well as a combination of two of these agents. Each trial must have been at least 6 weeks long. A trial will be considered unsuccessful if the medication was discontinued because of intolerable side-effects. The child should be in treatment with a community psychiatrist to whom they will return upon completion of the study. Current CGAS score less than 50 EXCLUSION CRITERIA: Children with BPD Full scale IQ less than 80 Meets criteria for substance use disorder in the three months prior to randomization Currently pregnant, lactating, or sexually active without using a barrier method of contraception Previous treatment with clozapine History of seizures History of leukopenia or agranulocytosis Presence of an unstable medical illness INCLUSION CRITERIA: CONTROLS Control subjects will be age- and sex- matched to the BPD subjects. They will have normal physical and neurological examinations, and an identified primary care physician. Both control subjects and their first-degree relatives must be free of current or past psychopathology. EXCLUSION CRITERIA: CONTROLS I.Q less than 80; ongoing medical illness; neurologic disorder (including seizures); pregnancy; meeting past or present criteria for any diagnosis on the K-SADS-PL; meeting criterion A of post-traumatic stress disorder (exposure to a traumatic event).
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Arms and Interventions
| Intervention/Treatment |
| --- |
|Drug: Clozapine|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HV, Psychophysiology, Structural MRI, Genetics, Bipolar Disorder, Children and Adolescents, Clozapine, Placebo, Treatment-Refractory, Bipolar, Healthy Volunteer, BPD, Normal Control
|
|
NCT00001652
|
The Evaluation and Follow-up of Patients With Bipolar Disorder
|
The purpose of this research protocol is to screen and enroll individuals who have bipolar disorder and to track each person's course of illness in order to study the long-term course of illness and to elucidate possible clinical and biological predictors of acute and sustained treatment response. As a part of this protocol, subjects will: systematically be administered psychiatric rating scales such as the life-chart method (LCM) for daily assessment of mood, sleep, and behavior; be asked to participate in non-invasive research procedures, such as blood drawing for measurement of thyroid antibodies and intracellular calcium; and be medicated as is clinically appropriate. This protocol also serves as a stepping stone to other protocols such as the comparative acute and long-term efficacy of three antidepressants (#95-M-0129), and the efficacy of omega-3 fatty acids (#00-M-0004), for which separate written informed consents are obtained. Patients in this study are participants in the larger NIMH-Stanley Foundation Bipolar Network (SFBN), which involves six academic sites focused on better understanding the long-term course and treatment of the illness. The current protocol thus serves as an entry point for individuals with bipolar disorder for screening and detailed longitudinal assessment both prior to and in between more formal blind randomized IRB approved treatment protocols.
|
The purpose of this research protocol is to screen and enroll individuals who have bipolar disorder and to track each person's course of illness in order to study the long-term course of illness and to elucidate possible clinical and biological predictors of acute and sustained treatment response. As a part of this protocol, subjects will: systematically be administered psychiatric rating scales such as the life-chart method (LCM) for daily assessment of mood, sleep, and behavior; be asked to participate in non-invasive research procedures, such as blood drawing for measurement of thyroid antibodies and intracellular calcium; and be medicated as is clinically appropriate. This protocol also serves as a stepping stone to other protocols such as the comparative acute and long-term efficacy of three antidepressants (#95-M-0129), and the efficacy of omega-3 fatty acids (#00-M-0004), for which separate written informed consents are obtained. Patients in this study are participants in the larger NIMH-Stanley Foundation Bipolar Network (SFBN), which involves six academic sites focused on better understanding the long-term course and treatment of the illness. The current protocol thus serves as an entry point for individuals with bipolar disorder for screening and detailed longitudinal assessment both prior to and in between more formal blind randomized IRB approved treatment protocols.
|
The Evaluation and Naturalistic Follow-up of Patients With Bipolar Disorder
|
Bipolar Disorder
|
Subjects must fulfill DSM-IV criteria for Bipolar I disorder (BPI), Bipolar II disorder (BPII), Bipolar Disorder not otherwise specified (BPNOS), or schizoaffective disorder bipolar type.~Subjects must be competent to comprehend the purpose of the study and to provide written informed consent and be willing to participate in detailed longitudinal follow-up.~Subjects will undergo complete psychiatric diagnostic interview (SCID--DSM-IV), medical, neurological, and laboratory examinations (as appropriate such as EKG, renal and liver function tests, serum electrolytes, urinalysis, HIV, hepatitis B, pregnancy testing, and urine drug screen for the presence of psychoactive drugs and drugs of abuse).~Subjects must be at least 18 years old.~Subjects should have no general medical illness that is primary (i.e. appears to be causing the mood disorder), or contraindicates the use of conventional and study medications under other protocols.~Women participants of child bearing potential must be nongravid, nonnursing, and using acceptable method of birth control such as intrauterine device, diaphragm with contraceptive foam, or condom with spermicide.~Subjects must not have alcohol or substance use or dependence of sufficient magnitude to require independent, concurrent treatment intervention (excluding self-help groups), i.e., hospitalization, day treatment programs, or counselor visits.
| null | null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Course of Illness, Life-Charting, Cerebrospinal Fluid, Diagnostic Tests, Cognitive Testing, Bipolar Disorder
|
Bipolar Disorder, Bipolar and Related Disorders, Mood Disorders, Mental Disorders
|
The Evaluation and Follow-up of Patients With Bipolar Disorder
Study Overview
=================
Brief Summary
-----------------
The purpose of this research protocol is to screen and enroll individuals who have bipolar disorder and to track each person's course of illness in order to study the long-term course of illness and to elucidate possible clinical and biological predictors of acute and sustained treatment response. As a part of this protocol, subjects will: systematically be administered psychiatric rating scales such as the life-chart method (LCM) for daily assessment of mood, sleep, and behavior; be asked to participate in non-invasive research procedures, such as blood drawing for measurement of thyroid antibodies and intracellular calcium; and be medicated as is clinically appropriate. This protocol also serves as a stepping stone to other protocols such as the comparative acute and long-term efficacy of three antidepressants (#95-M-0129), and the efficacy of omega-3 fatty acids (#00-M-0004), for which separate written informed consents are obtained. Patients in this study are participants in the larger NIMH-Stanley Foundation Bipolar Network (SFBN), which involves six academic sites focused on better understanding the long-term course and treatment of the illness. The current protocol thus serves as an entry point for individuals with bipolar disorder for screening and detailed longitudinal assessment both prior to and in between more formal blind randomized IRB approved treatment protocols.
Detailed Description
-----------------
The purpose of this research protocol is to screen and enroll individuals who have bipolar disorder and to track each person's course of illness in order to study the long-term course of illness and to elucidate possible clinical and biological predictors of acute and sustained treatment response. As a part of this protocol, subjects will: systematically be administered psychiatric rating scales such as the life-chart method (LCM) for daily assessment of mood, sleep, and behavior; be asked to participate in non-invasive research procedures, such as blood drawing for measurement of thyroid antibodies and intracellular calcium; and be medicated as is clinically appropriate. This protocol also serves as a stepping stone to other protocols such as the comparative acute and long-term efficacy of three antidepressants (#95-M-0129), and the efficacy of omega-3 fatty acids (#00-M-0004), for which separate written informed consents are obtained. Patients in this study are participants in the larger NIMH-Stanley Foundation Bipolar Network (SFBN), which involves six academic sites focused on better understanding the long-term course and treatment of the illness. The current protocol thus serves as an entry point for individuals with bipolar disorder for screening and detailed longitudinal assessment both prior to and in between more formal blind randomized IRB approved treatment protocols.
Official Title
-----------------
The Evaluation and Naturalistic Follow-up of Patients With Bipolar Disorder
Conditions
-----------------
Bipolar Disorder
Participation Criteria
=================
Eligibility Criteria
-----------------
Subjects must fulfill DSM-IV criteria for Bipolar I disorder (BPI), Bipolar II disorder (BPII), Bipolar Disorder not otherwise specified (BPNOS), or schizoaffective disorder bipolar type. Subjects must be competent to comprehend the purpose of the study and to provide written informed consent and be willing to participate in detailed longitudinal follow-up. Subjects will undergo complete psychiatric diagnostic interview (SCID--DSM-IV), medical, neurological, and laboratory examinations (as appropriate such as EKG, renal and liver function tests, serum electrolytes, urinalysis, HIV, hepatitis B, pregnancy testing, and urine drug screen for the presence of psychoactive drugs and drugs of abuse). Subjects must be at least 18 years old. Subjects should have no general medical illness that is primary (i.e. appears to be causing the mood disorder), or contraindicates the use of conventional and study medications under other protocols. Women participants of child bearing potential must be nongravid, nonnursing, and using acceptable method of birth control such as intrauterine device, diaphragm with contraceptive foam, or condom with spermicide. Subjects must not have alcohol or substance use or dependence of sufficient magnitude to require independent, concurrent treatment intervention (excluding self-help groups), i.e., hospitalization, day treatment programs, or counselor visits.
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Course of Illness, Life-Charting, Cerebrospinal Fluid, Diagnostic Tests, Cognitive Testing, Bipolar Disorder
|
||||
NCT04499898
|
Carvedilol Versus Endoscopic Band Ligation for Primary Prophylaxis of Oesophageal Variceal Bleeding
|
Carvedilol versus endoscopic band ligation for primary prophylaxis of oesophageal variceal bleeding in cirrhotic patients with arterial hypertension
|
A Randomized controlled trial of carvedilol versus endoscopic band ligation for primary prophylaxis of oesophageal variceal bleeding in cirrhotic patients with arterial hypertension
|
Randomized Controlled Trial of Carvedilol Versus Endoscopic Band Ligation for Primary Prophylaxis of Oesophageal Variceal Bleeding in Cirrhotic Patients With Arterial Hypertension
|
Esophageal Varices
|
* Drug: Carvedilol
* Procedure: Endoscopic band ligation
|
Inclusion Criteria:~• Aged >18 years~Cirrhotic patients with arterial hypertension~Endoscopic evidence of medium/large-sized esophageal varices~Exclusion Criteria:~• History of variceal bleeding or previous primary prevention of varices.~Portal vein thrombosis or previous porto-systemic shunts as TIPS.~Patients on drugs affecting portal pressure (beta blockers, nitrates).~Advanced cardiovascular disease including acute myocardial infarction, atrio-ventricular block, congestive heart failure, chronic peripheral ischemia, severe bradycardia.~Patients with severe respiratory diseases (COPD, bronchial asthma).~Uncontrolled diabetes mellitus~Renal impairment~Hepatocellular carcinoma~Allergy to carvedilol~Pregnancy or lactation
|
18 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with the first variceal bleeding within 1 year | The number of patients with the first variceal bleeding within 1 year | 1 year |
|
Carvedilol, Adrenergic beta-Antagonists, Adrenergic Antagonists, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs, Antihypertensive Agents, Antioxidants, Protective Agents, Calcium Channel Blockers, Membrane Transport Modulators, Calcium-Regulating Hormones and Agents, Vasodilator Agents, Adrenergic alpha-1 Receptor Antagonists, Adrenergic alpha-Antagonists
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carvedilol<br>Carvedilol | Drug: Carvedilol<br>* Carvedilol<br>* Other names: carvid;|
| Active Comparator: Band Ligation<br>Band Ligation | Procedure: Endoscopic band ligation<br>* Endoscopic band ligation<br>* Other names: band ligation;|
|
Carvedilol Versus Endoscopic Band Ligation for Primary Prophylaxis of Oesophageal Variceal Bleeding
Study Overview
=================
Brief Summary
-----------------
Carvedilol versus endoscopic band ligation for primary prophylaxis of oesophageal variceal bleeding in cirrhotic patients with arterial hypertension
Detailed Description
-----------------
A Randomized controlled trial of carvedilol versus endoscopic band ligation for primary prophylaxis of oesophageal variceal bleeding in cirrhotic patients with arterial hypertension
Official Title
-----------------
Randomized Controlled Trial of Carvedilol Versus Endoscopic Band Ligation for Primary Prophylaxis of Oesophageal Variceal Bleeding in Cirrhotic Patients With Arterial Hypertension
Conditions
-----------------
Esophageal Varices
Intervention / Treatment
-----------------
* Drug: Carvedilol
* Procedure: Endoscopic band ligation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: • Aged >18 years Cirrhotic patients with arterial hypertension Endoscopic evidence of medium/large-sized esophageal varices Exclusion Criteria: • History of variceal bleeding or previous primary prevention of varices. Portal vein thrombosis or previous porto-systemic shunts as TIPS. Patients on drugs affecting portal pressure (beta blockers, nitrates). Advanced cardiovascular disease including acute myocardial infarction, atrio-ventricular block, congestive heart failure, chronic peripheral ischemia, severe bradycardia. Patients with severe respiratory diseases (COPD, bronchial asthma). Uncontrolled diabetes mellitus Renal impairment Hepatocellular carcinoma Allergy to carvedilol Pregnancy or lactation
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carvedilol<br>Carvedilol | Drug: Carvedilol<br>* Carvedilol<br>* Other names: carvid;|
| Active Comparator: Band Ligation<br>Band Ligation | Procedure: Endoscopic band ligation<br>* Endoscopic band ligation<br>* Other names: band ligation;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with the first variceal bleeding within 1 year | The number of patients with the first variceal bleeding within 1 year | 1 year |
|
||
NCT02877173
|
A Safety/Efficacy Study of Alprostadil Liposomes for Injection to Treat Lower Extremity Arteriosclerosis Obliterans
|
A phase II,randomized,double-blind,multi-doses,positive drug parallel controlled,multi-center clinical trial to evaluate initially the efficacy and safety of alprostadil liposomes for injection in the treatment of atherosclerotic occlusive disease of the lower extremities.
|
This is a phase 2 dose-finding study evaluating initially the efficacy and safety of alprostadil liposomes for injection in the treatment of atherosclerotic occlusive disease of the lower extremities at different dose strengths.The total duration of subject participation will be approximately 5 weeks,consisting of a 2-week run-in period,3-week treatment and safety follow-up period.~Subjects will sign the informed consent form(ICF) at a screening visit and will be assigned a subject identifier.Subjects meeting all inclusion/exclusion criteria and who have successfully completed all protocol procedures at screening will enter the 2-week run-in.Following the 2-week run-in period,eligible subjects will be randomized(1:1:1:1) to one of the following double-blind treatment groups:~Group A : Alprostadil Liposomes for Injection at low dose:20ug,once a day(QD); Group B : Alprostadil Liposomes for Injection at medium dose:40ug,QD Group C : Alprostadil Liposomes for Injection at high dose:60ug,QD Group D(Positive Control Group) : Alprostadil Injection:10ug,QD All treatments will be delivered by intravenously guttae.A subject will be consider to have completed the study when they have completed all phase of the study including run-in,randomization,the randomized treatment and efficacy and safety follow-up phase.
|
Efficacy and Safety of Alprostadil Liposomes for Injection in the Treatment of Atherosclerotic Occlusive Disease of the Lower Extremities-A Phase II Multi-center Randomised Controlled Trial
|
Arteriosclerosis Obliterans
|
* Drug: Alprostadil Liposomes for Injection
* Drug: Alprostadil Injection
|
Inclusion Criteria:~An established clinical history of Atherosclerotic Occlusive Disease of the Lower Extremities in accordance with the definition by Chinese Medical Association(2015).~Age>40~Atherosclerotic Occlusive Disease of the Lower Extremities diagnosis~Arterial ischemia of the lower extremities pulsation has been weakened or disappeared.~Ankle brachial index(ABI) less than or equal to 0.9~Diagnosis of artery stenosis or occlusion with imaging tests,including Doppler ultrasonography,CT angiogram(CTA),magnetic resonance angiography (MRA) or digital subtraction angiography(DSA) within 1 month prior to Screening.~Fontaine stage classification:Stage II~Distance of asymptomatic disease and claudication between 50m to 800m(The treadmill setting:pace at 3 km/h,incline at 12%).Subjects have intermittent claudication twice within 1 week prior to enrollment visit(Baseline is defined as the first measurement.Change from baseline in P-values less than or equal to 25%).~Age:80 years old or younger.~Intermittent claudication has been in stable condition in the last 6 months.And there was no history of exacerbations within 3 months prior to enrollment visit.~Informed Consent:A signed and dated written informed consent prior to study participation.~Exclusion Criteria:~Subjects who have cardiac disease including caradiac failure,arrhythmias,coronary disease,mitral or aortic stenosis.Subjects with a recent history of myocardial infarction within the past 6 months are to be excluded.~Subjects who have pneumonedema,pulmonary infiltrates,interstitial pneumonia,severe chronic obstructive airway disorders or respiratory insufficiency confirmed by clinical examination.~Liver:Subjects with abnormal liver function tests defined as aspartate aminotransferase(AST) or alanine aminotransferase(ALT) greater than equal to 1.5 times upper limit of normal,as well as a diagnosis of primary liver disease will be excluded.~Renal:Subjects with abnormal kidney function tests defined as Creatinine clearance rate(SCr) greater than or equal to upper limit of normal.~Clinically Uncontrolled Hypertension:Subjects who have clinically significant uncontrolled hypertension(Systolic blood pressure:greater than or equal to 180mmHg;Or diastolic blood pressure:greater than or equal to 110mmHg).~Ankle systolic pressure is less than or equal to 50mmHg.~Subjects with affected limbs surgery or endovascular treatment within 3 months prior to Screening.Subjects who received Prostanoids within the past 1 week are to be excluded.~Subjects who received walking rehabilitation training successfully within the past 6 months.~Subjects with a diagnosis of other diseases such as lower limb joint disorder,spinal lesions,neuropathy,serious lung and heart conditions which may impact intermittent claudication will be excluded.~Subjects who have inflammation of the vascular disease including Takayasu's arteritis,edema perivascular.~Subjects with active peptic ulcerease or bleeding tendency will be excluded.~Glaucoma:Subjects with a diagnosis of glaucoma or high intraocular pressure will be excluded.~Subjects who are medically unable to withhold their vasodilator including naftidrofuryl,pentoxy,buflomedil or cilostazol will be excluded.~Subjects who received any powerful analgesic within 1 month perior to Screening.~Subjects with a history of psychiatric disease or Alzheimer's Disease.~Cancer:Subjects with a diagnosis of cancer will be excluded.~Drug Allergy:Subjects who have a history of any componet of Alprostadil Injection.~Previous Participation:Subjects who were previously enrolled in any clinical trial within 1 month period to Screening.~Pregnancy:Women who are pregnant or lactating or women of childbearing potential who are not using an acceptable method of contraception.~Subjects,who in the opinion of the Investigator,will not be fit for this study.
|
40 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in distance of asymptomatic disease and claudication after 3 weeks of treatment. | Unit of distance of asymptomatic disease and claudication:meters | After 3 weeks of treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in maximun distance of claudication after 3 weeks of treatment. | Unit of maximun distance of claudication :meters | After 3 weeks of treatment |
| Change from baseline in distance of asymptomatic disease and claudication and in maximum distance of claudication after 2 weeks of treatment. | Unit of distance of asymptomatic disease and claudication:meters | After 2 weeks of treatment |
| The proportion of patients to treatment failure. | The treatment failure is defined as arteriosclerosis obliterans(ASO) exacerbation that has necessary to change chemotherapy or have interventional operation. | After 3 weeks of treatment |
| Incidence of Adverse Events(AEs) | The safety endpoints for this study include:~AEs~Vital Sign Measurements~Physical examination~Clinical Laboratory Evaluations | over 3 weeks of treatment |
|
Arteriosclerosis Obliterans, Atherosclerotic Occlusive Disease of the Lower Extremities, Intermittent Claudication
|
Alprostadil, Platelet Aggregation Inhibitors, Vasodilator Agents, Urological Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alprostadil Liposomes for Injection<br>Alprostadil Liposomes for Injection at low dose:20ug,once a day,continuous administration for 3 weeks; Alprostadil Liposomes for Injection at medium dose:40ug,once a day,continuous administration for 3 weeks; Alprostadil Liposomes for Injection at high dose:60ug,once a day,continuous administration for 3 weeks; | Drug: Alprostadil Liposomes for Injection<br>* 3 doses of Alprostadil Liposomes for Injection are 20ug/q.d,40ug/q.d,60ug/q.d.All groups will be continuous administration for 3 weeks.<br>* Other names: No other names;|
| Active Comparator: Alprostadil Injection<br>Alprostadil Injection:10ug,once a day,continuous administration for 3 weeks; | Drug: Alprostadil Injection<br>* Alprostadil Injection(the positive control group):10ug/q.d,continuous administration for 3 weeks.<br>* Other names: No other names;|
|
A Safety/Efficacy Study of Alprostadil Liposomes for Injection to Treat Lower Extremity Arteriosclerosis Obliterans
Study Overview
=================
Brief Summary
-----------------
A phase II,randomized,double-blind,multi-doses,positive drug parallel controlled,multi-center clinical trial to evaluate initially the efficacy and safety of alprostadil liposomes for injection in the treatment of atherosclerotic occlusive disease of the lower extremities.
Detailed Description
-----------------
This is a phase 2 dose-finding study evaluating initially the efficacy and safety of alprostadil liposomes for injection in the treatment of atherosclerotic occlusive disease of the lower extremities at different dose strengths.The total duration of subject participation will be approximately 5 weeks,consisting of a 2-week run-in period,3-week treatment and safety follow-up period. Subjects will sign the informed consent form(ICF) at a screening visit and will be assigned a subject identifier.Subjects meeting all inclusion/exclusion criteria and who have successfully completed all protocol procedures at screening will enter the 2-week run-in.Following the 2-week run-in period,eligible subjects will be randomized(1:1:1:1) to one of the following double-blind treatment groups: Group A : Alprostadil Liposomes for Injection at low dose:20ug,once a day(QD); Group B : Alprostadil Liposomes for Injection at medium dose:40ug,QD Group C : Alprostadil Liposomes for Injection at high dose:60ug,QD Group D(Positive Control Group) : Alprostadil Injection:10ug,QD All treatments will be delivered by intravenously guttae.A subject will be consider to have completed the study when they have completed all phase of the study including run-in,randomization,the randomized treatment and efficacy and safety follow-up phase.
Official Title
-----------------
Efficacy and Safety of Alprostadil Liposomes for Injection in the Treatment of Atherosclerotic Occlusive Disease of the Lower Extremities-A Phase II Multi-center Randomised Controlled Trial
Conditions
-----------------
Arteriosclerosis Obliterans
Intervention / Treatment
-----------------
* Drug: Alprostadil Liposomes for Injection
* Drug: Alprostadil Injection
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: An established clinical history of Atherosclerotic Occlusive Disease of the Lower Extremities in accordance with the definition by Chinese Medical Association(2015). Age>40 Atherosclerotic Occlusive Disease of the Lower Extremities diagnosis Arterial ischemia of the lower extremities pulsation has been weakened or disappeared. Ankle brachial index(ABI) less than or equal to 0.9 Diagnosis of artery stenosis or occlusion with imaging tests,including Doppler ultrasonography,CT angiogram(CTA),magnetic resonance angiography (MRA) or digital subtraction angiography(DSA) within 1 month prior to Screening. Fontaine stage classification:Stage II Distance of asymptomatic disease and claudication between 50m to 800m(The treadmill setting:pace at 3 km/h,incline at 12%).Subjects have intermittent claudication twice within 1 week prior to enrollment visit(Baseline is defined as the first measurement.Change from baseline in P-values less than or equal to 25%). Age:80 years old or younger. Intermittent claudication has been in stable condition in the last 6 months.And there was no history of exacerbations within 3 months prior to enrollment visit. Informed Consent:A signed and dated written informed consent prior to study participation. Exclusion Criteria: Subjects who have cardiac disease including caradiac failure,arrhythmias,coronary disease,mitral or aortic stenosis.Subjects with a recent history of myocardial infarction within the past 6 months are to be excluded. Subjects who have pneumonedema,pulmonary infiltrates,interstitial pneumonia,severe chronic obstructive airway disorders or respiratory insufficiency confirmed by clinical examination. Liver:Subjects with abnormal liver function tests defined as aspartate aminotransferase(AST) or alanine aminotransferase(ALT) greater than equal to 1.5 times upper limit of normal,as well as a diagnosis of primary liver disease will be excluded. Renal:Subjects with abnormal kidney function tests defined as Creatinine clearance rate(SCr) greater than or equal to upper limit of normal. Clinically Uncontrolled Hypertension:Subjects who have clinically significant uncontrolled hypertension(Systolic blood pressure:greater than or equal to 180mmHg;Or diastolic blood pressure:greater than or equal to 110mmHg). Ankle systolic pressure is less than or equal to 50mmHg. Subjects with affected limbs surgery or endovascular treatment within 3 months prior to Screening.Subjects who received Prostanoids within the past 1 week are to be excluded. Subjects who received walking rehabilitation training successfully within the past 6 months. Subjects with a diagnosis of other diseases such as lower limb joint disorder,spinal lesions,neuropathy,serious lung and heart conditions which may impact intermittent claudication will be excluded. Subjects who have inflammation of the vascular disease including Takayasu's arteritis,edema perivascular. Subjects with active peptic ulcerease or bleeding tendency will be excluded. Glaucoma:Subjects with a diagnosis of glaucoma or high intraocular pressure will be excluded. Subjects who are medically unable to withhold their vasodilator including naftidrofuryl,pentoxy,buflomedil or cilostazol will be excluded. Subjects who received any powerful analgesic within 1 month perior to Screening. Subjects with a history of psychiatric disease or Alzheimer's Disease. Cancer:Subjects with a diagnosis of cancer will be excluded. Drug Allergy:Subjects who have a history of any componet of Alprostadil Injection. Previous Participation:Subjects who were previously enrolled in any clinical trial within 1 month period to Screening. Pregnancy:Women who are pregnant or lactating or women of childbearing potential who are not using an acceptable method of contraception. Subjects,who in the opinion of the Investigator,will not be fit for this study.
Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alprostadil Liposomes for Injection<br>Alprostadil Liposomes for Injection at low dose:20ug,once a day,continuous administration for 3 weeks; Alprostadil Liposomes for Injection at medium dose:40ug,once a day,continuous administration for 3 weeks; Alprostadil Liposomes for Injection at high dose:60ug,once a day,continuous administration for 3 weeks; | Drug: Alprostadil Liposomes for Injection<br>* 3 doses of Alprostadil Liposomes for Injection are 20ug/q.d,40ug/q.d,60ug/q.d.All groups will be continuous administration for 3 weeks.<br>* Other names: No other names;|
| Active Comparator: Alprostadil Injection<br>Alprostadil Injection:10ug,once a day,continuous administration for 3 weeks; | Drug: Alprostadil Injection<br>* Alprostadil Injection(the positive control group):10ug/q.d,continuous administration for 3 weeks.<br>* Other names: No other names;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in distance of asymptomatic disease and claudication after 3 weeks of treatment. | Unit of distance of asymptomatic disease and claudication:meters | After 3 weeks of treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in maximun distance of claudication after 3 weeks of treatment. | Unit of maximun distance of claudication :meters | After 3 weeks of treatment |
| Change from baseline in distance of asymptomatic disease and claudication and in maximum distance of claudication after 2 weeks of treatment. | Unit of distance of asymptomatic disease and claudication:meters | After 2 weeks of treatment |
| The proportion of patients to treatment failure. | The treatment failure is defined as arteriosclerosis obliterans(ASO) exacerbation that has necessary to change chemotherapy or have interventional operation. | After 3 weeks of treatment |
| Incidence of Adverse Events(AEs) | The safety endpoints for this study include: AEs Vital Sign Measurements Physical examination Clinical Laboratory Evaluations | over 3 weeks of treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Arteriosclerosis Obliterans, Atherosclerotic Occlusive Disease of the Lower Extremities, Intermittent Claudication
|
NCT03170583
|
SJM Brady MRI Post Approval Study
|
The purpose of this post approval study is to evaluate the long-term safety of the FDA approved St. Jude Medical Tendril MRI™ lead implanted with a SJM Brady MRI implantable pulse generator (IPG) such as the Accent MRI™, Assurity MRI™, Endurity MRI™ pacemaker, or similar model (SJM Brady MRI System) in subjects with a standard bradycardia pacing indication.
|
This is a prospective, multi-center clinical study designed to evaluate the long-term safety of the Tendril MRI™ lead implanted with any SJM Brady MRI pacemaker or similar model (SJM Brady MRI system) in subjects with a standard bradycardia pacing indication through 60 months of follow up.~Additionally, the study will assess the safety of the pacemaker system in subject(s) undergoing clinically indicated MRI scan(s). Any enrolled subject implanted with the SJM Brady MRI system may be included in this evaluation if they are scheduled for or planning to have a MRI scan during the course of the study.
|
SJM Brady MRI Post Approval Study
|
Bradycardia
|
* Device: St. Jude Medical Tendril MRI™ lead
|
Inclusion Criteria:~Subject is able to provide informed consent for study participation (legally authorized representative is NOT acceptable).~Subject is at least 18 years of age or of legal age to give informed consent specific to state and national law.~Subject meets at least one of the following criteria:~Is an Accent MRI IDE study subject who is being rolled over into the SJM Brady MRI PAS and still has at least one Tendril MRI™ lead implanted with a SJM Brady MRI pacemaker such as the Accent MRI or similar model.~Is a subject who has been implanted with at least one Tendril MRI lead and a SJM Brady MRI pacemaker such as the Accent MRI or similar model, but is not part of the Accent MRI IDE study and will be enrolled within 30 days after implant.~Is a subject who will be implanted with at least one Tendril MRI lead and a SJM Brady MRI pacemaker such as the Accent MRI or similar model and will be consented either at or within 30 days before implant.~Subject is willing and able to comply with the prescribed follow-up tests and schedule of evaluations including MRI scan procedures.~Exclusion Criteria:~Subject has been enrolled or intends to participate in a clinical drug and/or device study with an active treatment arm or that has any procedures, which could confound the results of this trial.~Subject is not expected to be able to complete the study follow up schedule or duration due to any health condition such as has malignancy, is deemed a candidate for transplant or Ventricular Assist Device, or in hospice care.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from Tendril MRI RA lead-related complications through 60 months of follow up | | 60 months |
| Freedom from Tendril MRI RV lead-related complications through 60 months of follow up | | 60 months |
| MRI scan related complications rate through one-month following the MRI scan | | 1 month |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The complication rate of the Tendril MRI lead | | 60 months |
|
bradycardia, pacemaker, MRI scan
|
Bradycardia, Arrhythmias, Cardiac, Heart Diseases, Cardiovascular Diseases, Pathologic Processes
|
| Intervention/Treatment |
| --- |
|Device: St. Jude Medical Tendril MRI™ lead|pacemaker, leads|
|
SJM Brady MRI Post Approval Study
Study Overview
=================
Brief Summary
-----------------
The purpose of this post approval study is to evaluate the long-term safety of the FDA approved St. Jude Medical Tendril MRI™ lead implanted with a SJM Brady MRI implantable pulse generator (IPG) such as the Accent MRI™, Assurity MRI™, Endurity MRI™ pacemaker, or similar model (SJM Brady MRI System) in subjects with a standard bradycardia pacing indication.
Detailed Description
-----------------
This is a prospective, multi-center clinical study designed to evaluate the long-term safety of the Tendril MRI™ lead implanted with any SJM Brady MRI pacemaker or similar model (SJM Brady MRI system) in subjects with a standard bradycardia pacing indication through 60 months of follow up. Additionally, the study will assess the safety of the pacemaker system in subject(s) undergoing clinically indicated MRI scan(s). Any enrolled subject implanted with the SJM Brady MRI system may be included in this evaluation if they are scheduled for or planning to have a MRI scan during the course of the study.
Official Title
-----------------
SJM Brady MRI Post Approval Study
Conditions
-----------------
Bradycardia
Intervention / Treatment
-----------------
* Device: St. Jude Medical Tendril MRI™ lead
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is able to provide informed consent for study participation (legally authorized representative is NOT acceptable). Subject is at least 18 years of age or of legal age to give informed consent specific to state and national law. Subject meets at least one of the following criteria: Is an Accent MRI IDE study subject who is being rolled over into the SJM Brady MRI PAS and still has at least one Tendril MRI™ lead implanted with a SJM Brady MRI pacemaker such as the Accent MRI or similar model. Is a subject who has been implanted with at least one Tendril MRI lead and a SJM Brady MRI pacemaker such as the Accent MRI or similar model, but is not part of the Accent MRI IDE study and will be enrolled within 30 days after implant. Is a subject who will be implanted with at least one Tendril MRI lead and a SJM Brady MRI pacemaker such as the Accent MRI or similar model and will be consented either at or within 30 days before implant. Subject is willing and able to comply with the prescribed follow-up tests and schedule of evaluations including MRI scan procedures. Exclusion Criteria: Subject has been enrolled or intends to participate in a clinical drug and/or device study with an active treatment arm or that has any procedures, which could confound the results of this trial. Subject is not expected to be able to complete the study follow up schedule or duration due to any health condition such as has malignancy, is deemed a candidate for transplant or Ventricular Assist Device, or in hospice care.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Device: St. Jude Medical Tendril MRI™ lead|pacemaker, leads|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from Tendril MRI RA lead-related complications through 60 months of follow up | | 60 months |
| Freedom from Tendril MRI RV lead-related complications through 60 months of follow up | | 60 months |
| MRI scan related complications rate through one-month following the MRI scan | | 1 month |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The complication rate of the Tendril MRI lead | | 60 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bradycardia, pacemaker, MRI scan
|
|
NCT00683709
|
Specialized Clozapine Clinic for Bipolar and Schizoaffective Disorder
|
Bipolar Disorder (BD) and Schizoaffective Disorder (SA) clients.~determine if after 12 months of treatment with clozapine, the BMI changes with clients who are councelled as usual regarding weight gain while on Clozapine.~determine if after 12 months of treatment with clozapine, the BMI changes with intense, structured councelling about diet and exercise.
|
To determine whether the changes in BMI produced in subjects with Bipolar Disorder (BD) and Schizoaffective Disorder (SA) by 12 months of treatment with clozapine, can be diminished after an intense and highly structured intervention focused on diet and exercise, compared with the usual brief counseling regarding weight gain on this drug.
|
Metabolic Side Effects, Diet and Exercise Counseling and Brain Function in a Naturalistic Clinical Trial of Clozapine for Treatment Resistant Bipolar and Schizoaffective Disorder
|
Bipolar Affective Disorder, Schizoaffective Disorder
|
* Behavioral: Counselling as Usual
* Behavioral: CBT
|
Inclusion Criteria:~Clients diagnosed with bipolar disorder or schizoaffective disorder~Clients who respond poorly to treatment~Males and females ages 18 years or older~Clients who have had a trial of antipsychotics, incl. at least one atypical antipsychotic plus at least 2 mood stabilizers~Clients who are capable of providing informed consent~Exclusion Criteria:~Clients who take carbamazepine~Clients with a history of extremely low white blood counts~Clients with severe kidney, liver or heart disease, or heart operation~Clients are hypersensitive to clozapine~Clients who have a history of serious side effects after previous treatment with clozapine~Clients with alcohol or drugs abuse within the last 3 months~Clients who have a seizure disorder~Clients who have metal in the head, neck or eyes, shrapnel, bullets, or body piercing, a pacemaker, brain aneurism clips, cochlear implant, hearing aid, tens unit, spinal implant, or pregnancy. These safety measures are necessary because of the magnetic fields of the MRI scan.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increases in BMI in subjects with BD and SA after 12 months of clozapine treatment will be smaller in subjects treated with CBT ex/diet compared with those receiving CAU. | | 5 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse changes in plasma lipids, blood sugar, and fitness level will be greater in subjects treated with CBT ex/diet compared with those receiving CAU after 12 months of clozapine treatment. | | 5 years |
|
Bipolar and Schizoaffective Disorder, Clozapine, Metabolic Side Effects, Diet & Exercise, BMI
|
Psychotic Disorders, Mood Disorders, Bipolar Disorder, Schizophrenia Spectrum and Other Psychotic Disorders, Mental Disorders, Bipolar and Related Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Counselling as Usual<br>Discussing Clozapine medication, diet and exercise as per clinical protocol potential weight changes | Behavioral: Counselling as Usual<br>* 5 - 20 minutes, about the effects of clozapine on body weight, appetite, blood sugar and fats such as cholesterol and triglycerides in the blood, and how these might affect your health in the future.<br>|
| Cognitive Behavoural Therapy<br>Counselling about Clozapine medication, diet and exercise in a structured fashion using Cognitive Behavioural Therapy about potential weight changes | Behavioral: CBT<br>* 45 - 60 minutes individual treatment sessions focused on nutrition, exercise and weight control and will occur weekly for 4 weeks. After this, 10 group sessions focused on weight reduction will be held every 2 weeks. This will be followed by 6 group sessions focused on weight maintenance held every 2 weeks.<br>|
|
Specialized Clozapine Clinic for Bipolar and Schizoaffective Disorder
Study Overview
=================
Brief Summary
-----------------
Bipolar Disorder (BD) and Schizoaffective Disorder (SA) clients. determine if after 12 months of treatment with clozapine, the BMI changes with clients who are councelled as usual regarding weight gain while on Clozapine. determine if after 12 months of treatment with clozapine, the BMI changes with intense, structured councelling about diet and exercise.
Detailed Description
-----------------
To determine whether the changes in BMI produced in subjects with Bipolar Disorder (BD) and Schizoaffective Disorder (SA) by 12 months of treatment with clozapine, can be diminished after an intense and highly structured intervention focused on diet and exercise, compared with the usual brief counseling regarding weight gain on this drug.
Official Title
-----------------
Metabolic Side Effects, Diet and Exercise Counseling and Brain Function in a Naturalistic Clinical Trial of Clozapine for Treatment Resistant Bipolar and Schizoaffective Disorder
Conditions
-----------------
Bipolar Affective Disorder, Schizoaffective Disorder
Intervention / Treatment
-----------------
* Behavioral: Counselling as Usual
* Behavioral: CBT
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clients diagnosed with bipolar disorder or schizoaffective disorder Clients who respond poorly to treatment Males and females ages 18 years or older Clients who have had a trial of antipsychotics, incl. at least one atypical antipsychotic plus at least 2 mood stabilizers Clients who are capable of providing informed consent Exclusion Criteria: Clients who take carbamazepine Clients with a history of extremely low white blood counts Clients with severe kidney, liver or heart disease, or heart operation Clients are hypersensitive to clozapine Clients who have a history of serious side effects after previous treatment with clozapine Clients with alcohol or drugs abuse within the last 3 months Clients who have a seizure disorder Clients who have metal in the head, neck or eyes, shrapnel, bullets, or body piercing, a pacemaker, brain aneurism clips, cochlear implant, hearing aid, tens unit, spinal implant, or pregnancy. These safety measures are necessary because of the magnetic fields of the MRI scan.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Counselling as Usual<br>Discussing Clozapine medication, diet and exercise as per clinical protocol potential weight changes | Behavioral: Counselling as Usual<br>* 5 - 20 minutes, about the effects of clozapine on body weight, appetite, blood sugar and fats such as cholesterol and triglycerides in the blood, and how these might affect your health in the future.<br>|
| Cognitive Behavoural Therapy<br>Counselling about Clozapine medication, diet and exercise in a structured fashion using Cognitive Behavioural Therapy about potential weight changes | Behavioral: CBT<br>* 45 - 60 minutes individual treatment sessions focused on nutrition, exercise and weight control and will occur weekly for 4 weeks. After this, 10 group sessions focused on weight reduction will be held every 2 weeks. This will be followed by 6 group sessions focused on weight maintenance held every 2 weeks.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increases in BMI in subjects with BD and SA after 12 months of clozapine treatment will be smaller in subjects treated with CBT ex/diet compared with those receiving CAU. | | 5 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse changes in plasma lipids, blood sugar, and fitness level will be greater in subjects treated with CBT ex/diet compared with those receiving CAU after 12 months of clozapine treatment. | | 5 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bipolar and Schizoaffective Disorder, Clozapine, Metabolic Side Effects, Diet & Exercise, BMI
|
|
NCT02175433
|
A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Refractory or Relapsed Lymphoid Malignancies
|
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of AGS67E both without and with myeloid growth factor (GF) in subjects with refractory or relapsed lymphoid malignancies. Immunogenicity and anticancer activity of AGS67E will also be assessed.
|
The dose escalation study will have two parts:~Dose Escalation of AGS67E without myeloid growth factor (GF)~Dose Escalation of AGS67E with myeloid growth factor (GF)~Subjects will be enrolled sequentially into dose cohorts starting with AGS67E without GF.~All subjects will receive a single 30 minute intravenous (IV) infusion of AGS67E once every three weeks. Subjects will continue treatment until disease progression, intolerability of AGS67E, investigator decision or consent withdrawal.~This dose escalation will first determine the maximum tolerated dose (MTD) of AGS67E without GF and then determine the MTD of AGS67E with GF. Once an MTD has been established, the study may enroll subjects into respective expansion cohorts of 12 subjects each at doses recommended by the data review team (DRT) (expansion cohort without GF and/or expansion cohort with GF).~During dose escalation, the Data Review Team will review cumulative unaudited data on an interim basis to review subject safety, recommend exploring additional doses and/or schedules, or the expansion of existing cohorts.
|
A Phase 1 Study Evaluating Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Refractory or Relapsed Lymphoid Malignancies
|
Relapsed Lymphoid Malignancy, Refractory Lymphoid Malignancy
|
* Drug: AGS67E
|
Inclusion Criteria:~Refractory or relapsed chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HCL) or non-Hodgkin lymphoma (NHL) (including those of T cell origin)~Eastern Cooperative Oncology Group performance score (ECOG) ≤ 2~Negative pregnancy test (women of childbearing potential)~Hematologic function, as follows (no platelet transfusion within 2 weeks and no RBC transfusion within 4 days before the first dose of study drug)~Absolute neutrophil count (ANC) ≥ 1,000/μL~Platelets ≥ 75,000/μL~Hemoglobin ≥ 8 g/dL (may be transfused ≥ 5 days)~Renal function: serum creatinine ≤ 2.0 mg/dL and estimated creatinine clearance of ≥ 45 mL/min by the Cockcroft-Gault equation~Direct bilirubin ≤ 1.5 x upper limit of normal (ULN)~Serum albumin ≥ 2.5 g/dL~Aspartate aminotransferase (AST) ≤ 1.5 x ULN unless there is hepatic involvement, then 3 x ULN~Alanine aminotransferase (ALT) ≤ 1.5 x ULN unless there is hepatic involvement, then 3 x ULN~Sexually active fertile subjects, and their partners, must agree to use medically accepted double-barrier methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the study and at least 6 weeks after termination of study therapy~Exclusion Criteria:~Preexisting sensory and/or motor neuropathy Grade ≥ 2~Small molecule therapy, radiotherapy, immunotherapy, monoclonal antibodies, or chemotherapy within 2 weeks before first dose of study drug~Radioimmunotherapy within 4 weeks before first dose of study drug~Use of any investigational drug (including marketed drugs not approved for this indication) within 14 days prior to the first dose of study drug~Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 2 weeks before the first dose of study drug (See Appendix F for list of excluded drugs)~Anti Graft-Versus-Host Disease (GVHD) therapy within 12 weeks before the first dose of study drug~Platelet transfusion within 2 weeks and RBC transfusion within 4 days before the first dose of study drug~Known central nervous system (CNS) disease~History of other primary malignancy (including myeloid malignancy, e.g., myelodysplastic syndrome), unless~Curatively resected nonmelanomatous skin cancer~Other malignancy curatively treated with no known active disease present and no systemic treatment administered for 3 years before the first dose of study drug~Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of the first dose of study drug, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication~Women who are pregnant or lactating~Known HIV positive or AIDS~Positive Hepatitis B surface antigen test~Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy~Known sensitivity to any of the components of the investigational product AGS67E:~AGS67E~L-Histidine~α-trehalose dihydrate or~polysorbate 20~History of thromboembolic events (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) ≤ 2 weeks before the first dose of study drug and/or clinical diffuse intravascular coagulation (DIC)~Active infection requiring treatment ≤7 days before the first dose of study drug~Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study~Any medical, psychiatric, addictive or other disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of adverse events | | up to 34 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-21) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Anti-Drug Antibody (ADA) formation to the fully human monoclonal antibody (AGS67C) and antibody-drug conjugate (AGS67E) | | Up to 34 months |
| Incidence of tumor response | Tumor response is defined as either a complete response (CR) or partial response (PR) | Up to 34 months |
| Objective response rate (ORR) | ORR for a cohort is defined as the percentage of subjects who experience a best response of either complete response (CR) or partial response (PR) in that cohort. | Up to 34 months |
|
Refractory or relapsed chronic lymphocytic leukemia (CLL) prolymphocytic leukemia (PLL), Relapsed lymphoid malignancy, Refractory lymphoid malignancy, Pharmacokinetics of AGS67E, hairy cell leukemia (HCL), AGS67C, non-Hodgkin lymphoma (NHL), AGS67E
|
AGS67E, Immunologic Factors, Immunoconjugates, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation of AGS67E 0.05 mg/kg Without GF<br>Participants will receive 0.05 milligram per kilogram (mg/kg) AGS67E without growth factor (GF) by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 0.1 mg/kg Without GF<br>Participants will receive 0.1 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 0.3 mg/kg Without GF<br>Participants will receive 0.3 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 0.6 mg/kg Without GF<br>Participants will receive 0.6 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 0.9 mg/kg Without GF<br>Participants will receive 0.9 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 1.2 mg/kg Without GF<br>Participants will receive 1.2 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Expansion of AGS67E 0.9 mg/kg Without GF<br>Participants will receive 0.9 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 1.2 mg/kg With GF<br>Participants will receive 1.2 mg/kg AGS67E with GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 1.5 mg/kg With GF<br>Participants will receive 1.5 mg/kg AGS67E with GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 1.8 mg/kg With GF<br>Participants will receive 1.8 mg/kg AGS67E with GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Expansion of AGS67E 1.5 mg/kg With GF<br>Participants will receive 1.5 mg/kg AGS67E with GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
|
A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Refractory or Relapsed Lymphoid Malignancies
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of AGS67E both without and with myeloid growth factor (GF) in subjects with refractory or relapsed lymphoid malignancies. Immunogenicity and anticancer activity of AGS67E will also be assessed.
Detailed Description
-----------------
The dose escalation study will have two parts: Dose Escalation of AGS67E without myeloid growth factor (GF) Dose Escalation of AGS67E with myeloid growth factor (GF) Subjects will be enrolled sequentially into dose cohorts starting with AGS67E without GF. All subjects will receive a single 30 minute intravenous (IV) infusion of AGS67E once every three weeks. Subjects will continue treatment until disease progression, intolerability of AGS67E, investigator decision or consent withdrawal. This dose escalation will first determine the maximum tolerated dose (MTD) of AGS67E without GF and then determine the MTD of AGS67E with GF. Once an MTD has been established, the study may enroll subjects into respective expansion cohorts of 12 subjects each at doses recommended by the data review team (DRT) (expansion cohort without GF and/or expansion cohort with GF). During dose escalation, the Data Review Team will review cumulative unaudited data on an interim basis to review subject safety, recommend exploring additional doses and/or schedules, or the expansion of existing cohorts.
Official Title
-----------------
A Phase 1 Study Evaluating Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Refractory or Relapsed Lymphoid Malignancies
Conditions
-----------------
Relapsed Lymphoid Malignancy, Refractory Lymphoid Malignancy
Intervention / Treatment
-----------------
* Drug: AGS67E
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Refractory or relapsed chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HCL) or non-Hodgkin lymphoma (NHL) (including those of T cell origin) Eastern Cooperative Oncology Group performance score (ECOG) ≤ 2 Negative pregnancy test (women of childbearing potential) Hematologic function, as follows (no platelet transfusion within 2 weeks and no RBC transfusion within 4 days before the first dose of study drug) Absolute neutrophil count (ANC) ≥ 1,000/μL Platelets ≥ 75,000/μL Hemoglobin ≥ 8 g/dL (may be transfused ≥ 5 days) Renal function: serum creatinine ≤ 2.0 mg/dL and estimated creatinine clearance of ≥ 45 mL/min by the Cockcroft-Gault equation Direct bilirubin ≤ 1.5 x upper limit of normal (ULN) Serum albumin ≥ 2.5 g/dL Aspartate aminotransferase (AST) ≤ 1.5 x ULN unless there is hepatic involvement, then 3 x ULN Alanine aminotransferase (ALT) ≤ 1.5 x ULN unless there is hepatic involvement, then 3 x ULN Sexually active fertile subjects, and their partners, must agree to use medically accepted double-barrier methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the study and at least 6 weeks after termination of study therapy Exclusion Criteria: Preexisting sensory and/or motor neuropathy Grade ≥ 2 Small molecule therapy, radiotherapy, immunotherapy, monoclonal antibodies, or chemotherapy within 2 weeks before first dose of study drug Radioimmunotherapy within 4 weeks before first dose of study drug Use of any investigational drug (including marketed drugs not approved for this indication) within 14 days prior to the first dose of study drug Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 2 weeks before the first dose of study drug (See Appendix F for list of excluded drugs) Anti Graft-Versus-Host Disease (GVHD) therapy within 12 weeks before the first dose of study drug Platelet transfusion within 2 weeks and RBC transfusion within 4 days before the first dose of study drug Known central nervous system (CNS) disease History of other primary malignancy (including myeloid malignancy, e.g., myelodysplastic syndrome), unless Curatively resected nonmelanomatous skin cancer Other malignancy curatively treated with no known active disease present and no systemic treatment administered for 3 years before the first dose of study drug Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of the first dose of study drug, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication Women who are pregnant or lactating Known HIV positive or AIDS Positive Hepatitis B surface antigen test Decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy Known sensitivity to any of the components of the investigational product AGS67E: AGS67E L-Histidine α-trehalose dihydrate or polysorbate 20 History of thromboembolic events (e.g., deep vein thrombosis (DVT) or pulmonary embolism (PE)) ≤ 2 weeks before the first dose of study drug and/or clinical diffuse intravascular coagulation (DIC) Active infection requiring treatment ≤7 days before the first dose of study drug Condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study Any medical, psychiatric, addictive or other disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation of AGS67E 0.05 mg/kg Without GF<br>Participants will receive 0.05 milligram per kilogram (mg/kg) AGS67E without growth factor (GF) by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 0.1 mg/kg Without GF<br>Participants will receive 0.1 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 0.3 mg/kg Without GF<br>Participants will receive 0.3 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 0.6 mg/kg Without GF<br>Participants will receive 0.6 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 0.9 mg/kg Without GF<br>Participants will receive 0.9 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 1.2 mg/kg Without GF<br>Participants will receive 1.2 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Expansion of AGS67E 0.9 mg/kg Without GF<br>Participants will receive 0.9 mg/kg AGS67E without GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 1.2 mg/kg With GF<br>Participants will receive 1.2 mg/kg AGS67E with GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 1.5 mg/kg With GF<br>Participants will receive 1.5 mg/kg AGS67E with GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Escalation of AGS67E 1.8 mg/kg With GF<br>Participants will receive 1.8 mg/kg AGS67E with GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
| Experimental: Dose Expansion of AGS67E 1.5 mg/kg With GF<br>Participants will receive 1.5 mg/kg AGS67E with GF by intravenous infusion once every three weeks. | Drug: AGS67E<br>* intravenous (IV) infusion<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of adverse events | | up to 34 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-21) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
| Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss) | | Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Anti-Drug Antibody (ADA) formation to the fully human monoclonal antibody (AGS67C) and antibody-drug conjugate (AGS67E) | | Up to 34 months |
| Incidence of tumor response | Tumor response is defined as either a complete response (CR) or partial response (PR) | Up to 34 months |
| Objective response rate (ORR) | ORR for a cohort is defined as the percentage of subjects who experience a best response of either complete response (CR) or partial response (PR) in that cohort. | Up to 34 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Refractory or relapsed chronic lymphocytic leukemia (CLL) prolymphocytic leukemia (PLL), Relapsed lymphoid malignancy, Refractory lymphoid malignancy, Pharmacokinetics of AGS67E, hairy cell leukemia (HCL), AGS67C, non-Hodgkin lymphoma (NHL), AGS67E
|
NCT03324009
|
2-stage Cervical Cancer Screening in Botswana
|
Cervical cancer is the leading cause of cancer death among women in Botswana. The burden of cervical cancer is largely related to the high prevalence of HIV in Botswana (22%), as HIV is known to be a significant risk factor for cervical cancer. Cervical cancer screening is life-saving and has been shown to reduce cervical cancer incidence in multiple settings. Yet, there is no consensus on appropriate screening algorithms for women living with HIV, across resource settings. Botswana is in a unique position, relative to its neighbors in Sub-Saharan Africa, in that there exists capacity for advanced screening modalities, including primary high risk human papilloma virus (hrHPV) testing and cytology-based screening. To address this issue, this study seeks to evaluate two-stage cervical cancer screening algorithms for women living with HIV in Botswana using hrHPV testing. The protocols include hrHPV testing followed by Pap Smear evaluation, VIA and colposcopy. These same participants will be invited back at one-year for cervical cancer screening using hrHPV testing (followed by triage testing) in order to inform guidelines on the frequency of HPV testing in women living with HIV. The evidence generated will be critical to guiding cervical cancer screening in HIV-infected women across resource settings.
|
Cervical cancer screening programs vary across settings and there is no clear guidance for effective screening programs for HIV-positive women. Evaluating the performance of algorithms that include human papillomavirus (HPV) DNA testing as first stage screening in high HIV prevalence settings like Botswana is essential for establishing an evidence-based strategy for cervical cancer screening in HIV-positive women.~This study seeks to evaluate the performance of two-stage cervical cancer screening algorithms using primary HPV testing in women living with HIV in Botswana. Second stage screening modalities include Papanicolaou (Pap) smear, visual inspection with acetic acid (VIA) and colposcopy.~The study will enroll 300 HIV positive women. For all 300 participants, gynecologic speculum exam will be performed and provider-collected cervical swabs will be collected for HPV testing and Pap smear preparation. HPV testing will be performed with either the commercially-available Cepheid Xpert® HPV Assay or a high throughput PCR platform. Pap smear will be prepared using standard technique at the site of collection.~Participants who test HPV-negative will have their Pap smear sent to the National Health Lab (NHL) for staining and pathologist evaluation. If the Pap smear is abnormal, they will be referred to colposcopy per current Botswana Cervical Cancer Prevention Guidelines.~Participants who test HPV-positive will also have their Pap smear reviewed, and will also be asked to return for colposcopy and will undergo further diagnosis and treatment for cervical cancer per national guidelines. At the colposcopy visit, a trained nurse will conduct VIA using the Botswana standard protocol. After application of acetic acid to the cervix, the nurse will record visual results as positive or negative. If VIA is positive based on assessment of the lesion(s), the nurse will record a recommendation for either cryotherapy or loop electrosurgical excision procedure (LEEP). Since all of these HPV-positive participants will undergo colposcopy, the participants will not be informed of the VIA results, as neither cryotherapy nor LEEP will be administered based on the VIA results. Rather, the participants will proceed to colposcopy and results of colposcopy will determine further diagnosis and treatment. This design enables us to assess the utility of the two-stage algorithms while providing the highest-quality follow-up to cervical cancer screening abnormalities in Botswana.~These same participants will be invited back at one-year for repeat cervical cancer screening using the same screening methods as at baseline. The data will inform guidelines on the frequency of hrHPV testing in women living with HIV.
|
Development of a Two-stage Cervical Cancer Screening Algorithm for Botswana
|
Cervical Cancer, HIV/AIDS
|
* Diagnostic Test: 2-stage screen
|
Inclusion Criteria:~≥25 years of age~HIV-positive~Competent to understand study procedures and give informed consent.~Exclusion Criteria:~Currently pregnant~Currently menstruating or having persistent vaginal discharge~Previous hysterectomy~Previous diagnosis of cervical cancer
|
25 Years
| null |
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective cohort
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance of HPV-Pap screening algorithm | Measurement of the sensitivity, specificity and positive predictive value of Pap smear in predicting cervical precancer and cancer in HPV positive, HIV positive women. | 2 months |
| Performance of HPV-VIA screening algorithm | Measurement of the sensitivity, specificity and positive predictive value of VIA in predicting cervical precancer and cancer in HPV positive, HIV positive women. | 2 months |
| Performance of HPV-Colposcopy screening algorithm | Measurement of the sensitivity, specificity and positive predictive value of Colposcopy in predicting cervical precancer and cancer in HPV positive, HIV positive women. | 6 months |
| Incident and persistent HPV infection at one-year follow-up | | 18 months |
| Incidence, persistence and progression of histopathologic abnormality at one-year follow-up | | 18 months |
|
Uterine Cervical Neoplasms, Uterine Neoplasms, Genital Neoplasms, Female, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Uterine Cervical Diseases, Uterine Diseases, Genital Diseases, Female, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Genital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2-stage screen<br>All patients will be enrolled in the two-stage cervical cancer screening protocol | Diagnostic Test: 2-stage screen<br>* Pap smear is currently the standard of care for cervical cancer screening in Botswana. In this study, participants will undergo HPV DNA testing at the time of Pap smear collection. If HPV DNA test is positive, they will be referred for colposcopy. Patients who have an HPV negative test but positive Pap smear will be referred for colposcopy per Botswana cervical cancer screening guidelines.<br>|
|
2-stage Cervical Cancer Screening in Botswana
Study Overview
=================
Brief Summary
-----------------
Cervical cancer is the leading cause of cancer death among women in Botswana. The burden of cervical cancer is largely related to the high prevalence of HIV in Botswana (22%), as HIV is known to be a significant risk factor for cervical cancer. Cervical cancer screening is life-saving and has been shown to reduce cervical cancer incidence in multiple settings. Yet, there is no consensus on appropriate screening algorithms for women living with HIV, across resource settings. Botswana is in a unique position, relative to its neighbors in Sub-Saharan Africa, in that there exists capacity for advanced screening modalities, including primary high risk human papilloma virus (hrHPV) testing and cytology-based screening. To address this issue, this study seeks to evaluate two-stage cervical cancer screening algorithms for women living with HIV in Botswana using hrHPV testing. The protocols include hrHPV testing followed by Pap Smear evaluation, VIA and colposcopy. These same participants will be invited back at one-year for cervical cancer screening using hrHPV testing (followed by triage testing) in order to inform guidelines on the frequency of HPV testing in women living with HIV. The evidence generated will be critical to guiding cervical cancer screening in HIV-infected women across resource settings.
Detailed Description
-----------------
Cervical cancer screening programs vary across settings and there is no clear guidance for effective screening programs for HIV-positive women. Evaluating the performance of algorithms that include human papillomavirus (HPV) DNA testing as first stage screening in high HIV prevalence settings like Botswana is essential for establishing an evidence-based strategy for cervical cancer screening in HIV-positive women. This study seeks to evaluate the performance of two-stage cervical cancer screening algorithms using primary HPV testing in women living with HIV in Botswana. Second stage screening modalities include Papanicolaou (Pap) smear, visual inspection with acetic acid (VIA) and colposcopy. The study will enroll 300 HIV positive women. For all 300 participants, gynecologic speculum exam will be performed and provider-collected cervical swabs will be collected for HPV testing and Pap smear preparation. HPV testing will be performed with either the commercially-available Cepheid Xpert® HPV Assay or a high throughput PCR platform. Pap smear will be prepared using standard technique at the site of collection. Participants who test HPV-negative will have their Pap smear sent to the National Health Lab (NHL) for staining and pathologist evaluation. If the Pap smear is abnormal, they will be referred to colposcopy per current Botswana Cervical Cancer Prevention Guidelines. Participants who test HPV-positive will also have their Pap smear reviewed, and will also be asked to return for colposcopy and will undergo further diagnosis and treatment for cervical cancer per national guidelines. At the colposcopy visit, a trained nurse will conduct VIA using the Botswana standard protocol. After application of acetic acid to the cervix, the nurse will record visual results as positive or negative. If VIA is positive based on assessment of the lesion(s), the nurse will record a recommendation for either cryotherapy or loop electrosurgical excision procedure (LEEP). Since all of these HPV-positive participants will undergo colposcopy, the participants will not be informed of the VIA results, as neither cryotherapy nor LEEP will be administered based on the VIA results. Rather, the participants will proceed to colposcopy and results of colposcopy will determine further diagnosis and treatment. This design enables us to assess the utility of the two-stage algorithms while providing the highest-quality follow-up to cervical cancer screening abnormalities in Botswana. These same participants will be invited back at one-year for repeat cervical cancer screening using the same screening methods as at baseline. The data will inform guidelines on the frequency of hrHPV testing in women living with HIV.
Official Title
-----------------
Development of a Two-stage Cervical Cancer Screening Algorithm for Botswana
Conditions
-----------------
Cervical Cancer, HIV/AIDS
Intervention / Treatment
-----------------
* Diagnostic Test: 2-stage screen
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥25 years of age HIV-positive Competent to understand study procedures and give informed consent. Exclusion Criteria: Currently pregnant Currently menstruating or having persistent vaginal discharge Previous hysterectomy Previous diagnosis of cervical cancer
Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective cohort
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2-stage screen<br>All patients will be enrolled in the two-stage cervical cancer screening protocol | Diagnostic Test: 2-stage screen<br>* Pap smear is currently the standard of care for cervical cancer screening in Botswana. In this study, participants will undergo HPV DNA testing at the time of Pap smear collection. If HPV DNA test is positive, they will be referred for colposcopy. Patients who have an HPV negative test but positive Pap smear will be referred for colposcopy per Botswana cervical cancer screening guidelines.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance of HPV-Pap screening algorithm | Measurement of the sensitivity, specificity and positive predictive value of Pap smear in predicting cervical precancer and cancer in HPV positive, HIV positive women. | 2 months |
| Performance of HPV-VIA screening algorithm | Measurement of the sensitivity, specificity and positive predictive value of VIA in predicting cervical precancer and cancer in HPV positive, HIV positive women. | 2 months |
| Performance of HPV-Colposcopy screening algorithm | Measurement of the sensitivity, specificity and positive predictive value of Colposcopy in predicting cervical precancer and cancer in HPV positive, HIV positive women. | 6 months |
| Incident and persistent HPV infection at one-year follow-up | | 18 months |
| Incidence, persistence and progression of histopathologic abnormality at one-year follow-up | | 18 months |
|
||
NCT01478854
|
Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide
|
The long term goal of this research is to establish whether NPC sparing RT techniques improve neurocognitive outcomes compared to conventional RT for brain tumors. If the proposed study demonstrates that NPC sparing RT is not associated with increased LR in the spared regions of the brain compared to conventional RT, it will ideally serve as the foundation for a future multi-institutional randomized controlled trial comparing neurocognitive outcomes in patients treated with NPC-sparing RT versus conventional radiation therapy.
|
Radiation therapy (RT) is an integral component of the management of brain tumors, but cognitive deficits following cranial irradiation are well documented. There is an association between damage to neural progenitor cells (NPC) and neurocognitive dysfunction. NPC are similarly known to play an important role in recovery from damage to the brain, including radiation-induced damage. However NPC are extremely sensitive to radiation. In spite of this information, current RT planning techniques do not limit the radiation dose to the NPC containing regions. Recent human studies have demonstrated that it is possible to use intensity modulated radiation therapy to reduce the radiation dose to NPC containing regions during RT for brain tumors, without compromising coverage of the tumor. We hypothesize that NPC-sparing RT will reduce neurocognitive decline following treatment for brain tumors, without compromising tumor local control. However, there is conflicting data regarding the role of NPC in the development of glioblastoma multiforme (GBM). Some studies suggest that GBM are derived from NPC whereas others have associated NPC with improved tumor control following therapy for GBM. Prior to evaluation of neurocognitive outcomes with NPC-sparing RT, it is therefore imperative to evaluate whether NPC-sparing RT techniques lead to increased LR in the spared NPC containing niches of the brain.~The proposed study is designed to evaluate LR in the spared regions of the brain following NPC sparing RT in patients with newly diagnosed GBM. Our research will consist of 3 specific aims: 1) Determine the LR rate at 1 year in the spared NPC containing niches in patients treated with NPC sparing RT for GBM; 2) Quantify the extent of radiation dose sparing to the NPC containing regions that is possible without compromising tumor coverage in patients with GBM; 3) Determine if it is feasible to evaluate cognitive function prospectively in patients undergoing NPC sparing RT for GBM.~The long term goal of this research is to establish whether NPC sparing RT techniques improve neurocognitive outcomes compared to conventional RT for brain tumors. If the proposed study demonstrates that NPC sparing RT is not associated with increased LR in the spared regions of the brain compared to conventional RT, it will ideally serve as the foundation for a future multi-institutional randomized controlled trial comparing neurocognitive outcomes in patients treated with NPC-sparing RT versus conventional radiation therapy.
|
A Prospective Trial of Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Glioblastoma Multiforme
|
Glioblastoma Multiforme
|
* Radiation: Radiation
* Drug: Chemotherapy
|
Inclusion Criteria:~Patient must have newly diagnosed Glioblastoma Multiforme (GBM).~Patient must have undergone surgical resection and must begin radiation within 12 weeks of this procedure.~Patients must not have received previous irradiation to the brain.~Patient must be at least 18 years of age~Karnofsky performance status of greater than 60%~Patient must receive temozolomide concurrent with and following radiation.~If a woman is of child-bearing potential, a negative urine or serum pregnancy test must be demonstrated prior to treatment. Women of childbearing potential and men must agree to use adequate contraception for the duration of study participation and for up to 12 weeks following the study. Should a women become pregnant or suspect she is pregnant while participating in this study she should inform her treating physician immediately.~Patient must have the ability to understand and the willingness to sign a written informed consent document.~All patients must be informed of the investigational nature of this study and must be given written informed consent in accordance with institutional and federal guidelines.~Exclusion Criteria:~Patients may not be receiving any other agents to treat their GBM~No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or other cancer from which the patient has been disease free for at least 2 years.~Patients with any other uncontrolled illness will be excluded.~Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. This applies to any woman who has not experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months). Male subjects must also agree to use effective contraception for the same period as above.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Local Recurrence in the Spared NPC Niches | Number of participants with local recurrence (LR) at 1 year in the spared neural progenitor cell (NPC) containing niches of the brain in patients treated with NPC sparing radiation therapy (RT) plus temozolomide for newly diagnosed glioblastoma multiforme (GBM). Local recurrence in spared area is defined as development of a new regions of T1 post gadolinium enhancement. | 1 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of NPC Sparing | The extent of NPC-sparing will be recorded for each patient. Patients will be binned into 4 groups according to the volume of NPC region that receives a certain dose as follows: 1) V5Gy≤50%; 2) V5Gy ≤20%; 3) V10Gy≤20%; 4) Doses higher than levels 1-3. | 1 year |
| Distance of Tumor to Spared NPC Niches | The X-, Y-, and Z- coordinate distances in centimeters will be recorded from the most proximal point of the planning tumor volume to the closest point of the spared NPC-containing niche. | 1 year |
| Change in Neurocognitive Function as Measured by Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Subtest | Change in mean score of neurocognitive function (processing speed) as measured by WAIS-IV (Coding subtest) in patients treated with NPC sparing radiation for newly diagnosed GBM. The coding subtest of WAIS-IV is a visual, paper and pencil task that requires individuals to match numbers with symbols based on a key at the top of the page (Coding) by drawing the correct symbol in the boxes provided. Coding measures visual processing speed, short-term visual memory, and the ability to shift the eyes efficiently back and forth between the key and the responses. This task requires fine motor skills (using a pencil) but does not require expressive language. Minimal demands are placed on receptive language. This task also assesses the ability to sustain focus and effort for a two minutes. The score is the total number of correct responses within a given time frame, which ranges from 0-135. A higher score reflects a better outcome. A negative value for change reflects a worse outcome. | Change from baseline to 6 months |
| Change in Neurocognitive Function as Measured by Trail Making Test | Change in mean score of neurocognitive function as measured by Trail Making test Parts A and B in patients treated with NPC sparing radiation for newly diagnosed GBM. The Trail making score is the number of seconds spent connecting numbered circles (1-13) to circles containing letters of the alphabet (A-L) in alternating sequential order. Score ranges from 0-150 for Part A and 0-300 for Part B. A higher score reflects greater neurocognitive impairment. Therefore, a negative value for change reflects an improvement in this measure, whereas a positive value reflects worsening impairment. | Change from baseline to 6 months |
| Change in Neurocognitive Function (Verbal Fluency) as Measured by Controlled Oral Word Association Test (COWAT) | Change in neurocognitive function (verbal fluency) as measured by COWAT in patients treated with NPC sparing radiation for newly diagnosed GBM. COWAT assesses verbal fluency by asking the participant to produce words for three designated letters. The test score is the total number of different words produced for all three letters. A higher score reflects a better outcome. Therefore, a positive value for change reflects an improvement in this measure. | Change from baseline to 6 months |
| Change in Neurocognitive Function (Total Recall, Delayed Recall, Recognition Discrimination) as Measured by Hopkins Verbal Learning Test-Revised (HVLT-R) | Change in total recall, delayed recall, and recognition discrimination index as measured by HVLT-R in patients treated with NPC sparing radiation for newly diagnosed GBM. 12-item word list, composed of four words from each of the three semantic categories which the patient must learn over three trials. For each trial, the subject is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The score for total recall is the sum of all the correctly-recalled words from each trial, for a maximum of 36. Delayed recall is assessed as the number of words freely recalled 20-25 minutes after the learning trials. Recognition is assessed after 20-25 minutes where the patient is read 24 words and is asked to say yes after words from the recall list (12 targets) and no after other words (12 distractors). RDI is the number of recalled target words minus the number of recalled distractor words. A higher score reflects a better outcome. | Change from baseline to 6 months |
| Radiation Dose to Spared NPC Region | The mean radiation dose (cGy) to spared NPC region (hippocampus, subventricular zone [SVZ]) in reference to site of lesion. | Day 1 of radiation therapy |
| Volume (cc) of NPC for Sparing Region | The volume of the NPC_for_sparing region as collected using the Pinnacle treatment planning system. | day 1 of radiation therapy |
|
Glioblastoma, Astrocytoma, Glioma, Neoplasms, Neuroepithelial, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms, Nerve Tissue
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neural Progenitor Cell Sparing Radiation with Temozolomide<br>All subjects are treated with neural progenitor cell sparing radiation to 60 Gy in 2 Gy per day, 30 fractions Concurrent and adjuvant temozolomide chemotherapy | Radiation: Radiation<br>* Patients will be treated to a total dose of 60 Gy with a once daily fractionation schedule of 2 Gy per fraction, administered five days per week. All patients will undergo CT simulation with intravenous contrast. In addition they will undergo MRI simulation with both T1 with gadolinium as well as FLAIR sequences. They will be treated in a supine position using an aquaplast mask system for immobilization. CT image data will be reconstructed in approximately 3 mm slice thickness and manually coregistered with T1 post-gadolinium and FLAIR sequence MRI.<br>Drug: Chemotherapy<br>* Temozolomide<br>|
|
Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide
Study Overview
=================
Brief Summary
-----------------
The long term goal of this research is to establish whether NPC sparing RT techniques improve neurocognitive outcomes compared to conventional RT for brain tumors. If the proposed study demonstrates that NPC sparing RT is not associated with increased LR in the spared regions of the brain compared to conventional RT, it will ideally serve as the foundation for a future multi-institutional randomized controlled trial comparing neurocognitive outcomes in patients treated with NPC-sparing RT versus conventional radiation therapy.
Detailed Description
-----------------
Radiation therapy (RT) is an integral component of the management of brain tumors, but cognitive deficits following cranial irradiation are well documented. There is an association between damage to neural progenitor cells (NPC) and neurocognitive dysfunction. NPC are similarly known to play an important role in recovery from damage to the brain, including radiation-induced damage. However NPC are extremely sensitive to radiation. In spite of this information, current RT planning techniques do not limit the radiation dose to the NPC containing regions. Recent human studies have demonstrated that it is possible to use intensity modulated radiation therapy to reduce the radiation dose to NPC containing regions during RT for brain tumors, without compromising coverage of the tumor. We hypothesize that NPC-sparing RT will reduce neurocognitive decline following treatment for brain tumors, without compromising tumor local control. However, there is conflicting data regarding the role of NPC in the development of glioblastoma multiforme (GBM). Some studies suggest that GBM are derived from NPC whereas others have associated NPC with improved tumor control following therapy for GBM. Prior to evaluation of neurocognitive outcomes with NPC-sparing RT, it is therefore imperative to evaluate whether NPC-sparing RT techniques lead to increased LR in the spared NPC containing niches of the brain. The proposed study is designed to evaluate LR in the spared regions of the brain following NPC sparing RT in patients with newly diagnosed GBM. Our research will consist of 3 specific aims: 1) Determine the LR rate at 1 year in the spared NPC containing niches in patients treated with NPC sparing RT for GBM; 2) Quantify the extent of radiation dose sparing to the NPC containing regions that is possible without compromising tumor coverage in patients with GBM; 3) Determine if it is feasible to evaluate cognitive function prospectively in patients undergoing NPC sparing RT for GBM. The long term goal of this research is to establish whether NPC sparing RT techniques improve neurocognitive outcomes compared to conventional RT for brain tumors. If the proposed study demonstrates that NPC sparing RT is not associated with increased LR in the spared regions of the brain compared to conventional RT, it will ideally serve as the foundation for a future multi-institutional randomized controlled trial comparing neurocognitive outcomes in patients treated with NPC-sparing RT versus conventional radiation therapy.
Official Title
-----------------
A Prospective Trial of Neural Progenitor Cell Sparing Radiation Therapy Plus Temozolomide for Newly Diagnosed Glioblastoma Multiforme
Conditions
-----------------
Glioblastoma Multiforme
Intervention / Treatment
-----------------
* Radiation: Radiation
* Drug: Chemotherapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient must have newly diagnosed Glioblastoma Multiforme (GBM). Patient must have undergone surgical resection and must begin radiation within 12 weeks of this procedure. Patients must not have received previous irradiation to the brain. Patient must be at least 18 years of age Karnofsky performance status of greater than 60% Patient must receive temozolomide concurrent with and following radiation. If a woman is of child-bearing potential, a negative urine or serum pregnancy test must be demonstrated prior to treatment. Women of childbearing potential and men must agree to use adequate contraception for the duration of study participation and for up to 12 weeks following the study. Should a women become pregnant or suspect she is pregnant while participating in this study she should inform her treating physician immediately. Patient must have the ability to understand and the willingness to sign a written informed consent document. All patients must be informed of the investigational nature of this study and must be given written informed consent in accordance with institutional and federal guidelines. Exclusion Criteria: Patients may not be receiving any other agents to treat their GBM No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, cervical carcinoma in situ, or other cancer from which the patient has been disease free for at least 2 years. Patients with any other uncontrolled illness will be excluded. Pregnant and breastfeeding women are excluded. Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 12 weeks after the study are excluded. This applies to any woman who has not experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months). Male subjects must also agree to use effective contraception for the same period as above.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neural Progenitor Cell Sparing Radiation with Temozolomide<br>All subjects are treated with neural progenitor cell sparing radiation to 60 Gy in 2 Gy per day, 30 fractions Concurrent and adjuvant temozolomide chemotherapy | Radiation: Radiation<br>* Patients will be treated to a total dose of 60 Gy with a once daily fractionation schedule of 2 Gy per fraction, administered five days per week. All patients will undergo CT simulation with intravenous contrast. In addition they will undergo MRI simulation with both T1 with gadolinium as well as FLAIR sequences. They will be treated in a supine position using an aquaplast mask system for immobilization. CT image data will be reconstructed in approximately 3 mm slice thickness and manually coregistered with T1 post-gadolinium and FLAIR sequence MRI.<br>Drug: Chemotherapy<br>* Temozolomide<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Local Recurrence in the Spared NPC Niches | Number of participants with local recurrence (LR) at 1 year in the spared neural progenitor cell (NPC) containing niches of the brain in patients treated with NPC sparing radiation therapy (RT) plus temozolomide for newly diagnosed glioblastoma multiforme (GBM). Local recurrence in spared area is defined as development of a new regions of T1 post gadolinium enhancement. | 1 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of NPC Sparing | The extent of NPC-sparing will be recorded for each patient. Patients will be binned into 4 groups according to the volume of NPC region that receives a certain dose as follows: 1) V5Gy≤50%; 2) V5Gy ≤20%; 3) V10Gy≤20%; 4) Doses higher than levels 1-3. | 1 year |
| Distance of Tumor to Spared NPC Niches | The X-, Y-, and Z- coordinate distances in centimeters will be recorded from the most proximal point of the planning tumor volume to the closest point of the spared NPC-containing niche. | 1 year |
| Change in Neurocognitive Function as Measured by Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV) Coding Subtest | Change in mean score of neurocognitive function (processing speed) as measured by WAIS-IV (Coding subtest) in patients treated with NPC sparing radiation for newly diagnosed GBM. The coding subtest of WAIS-IV is a visual, paper and pencil task that requires individuals to match numbers with symbols based on a key at the top of the page (Coding) by drawing the correct symbol in the boxes provided. Coding measures visual processing speed, short-term visual memory, and the ability to shift the eyes efficiently back and forth between the key and the responses. This task requires fine motor skills (using a pencil) but does not require expressive language. Minimal demands are placed on receptive language. This task also assesses the ability to sustain focus and effort for a two minutes. The score is the total number of correct responses within a given time frame, which ranges from 0-135. A higher score reflects a better outcome. A negative value for change reflects a worse outcome. | Change from baseline to 6 months |
| Change in Neurocognitive Function as Measured by Trail Making Test | Change in mean score of neurocognitive function as measured by Trail Making test Parts A and B in patients treated with NPC sparing radiation for newly diagnosed GBM. The Trail making score is the number of seconds spent connecting numbered circles (1-13) to circles containing letters of the alphabet (A-L) in alternating sequential order. Score ranges from 0-150 for Part A and 0-300 for Part B. A higher score reflects greater neurocognitive impairment. Therefore, a negative value for change reflects an improvement in this measure, whereas a positive value reflects worsening impairment. | Change from baseline to 6 months |
| Change in Neurocognitive Function (Verbal Fluency) as Measured by Controlled Oral Word Association Test (COWAT) | Change in neurocognitive function (verbal fluency) as measured by COWAT in patients treated with NPC sparing radiation for newly diagnosed GBM. COWAT assesses verbal fluency by asking the participant to produce words for three designated letters. The test score is the total number of different words produced for all three letters. A higher score reflects a better outcome. Therefore, a positive value for change reflects an improvement in this measure. | Change from baseline to 6 months |
| Change in Neurocognitive Function (Total Recall, Delayed Recall, Recognition Discrimination) as Measured by Hopkins Verbal Learning Test-Revised (HVLT-R) | Change in total recall, delayed recall, and recognition discrimination index as measured by HVLT-R in patients treated with NPC sparing radiation for newly diagnosed GBM. 12-item word list, composed of four words from each of the three semantic categories which the patient must learn over three trials. For each trial, the subject is instructed to listen carefully as the examiner reads the word list and attempt to memorize the words. The score for total recall is the sum of all the correctly-recalled words from each trial, for a maximum of 36. Delayed recall is assessed as the number of words freely recalled 20-25 minutes after the learning trials. Recognition is assessed after 20-25 minutes where the patient is read 24 words and is asked to say yes after words from the recall list (12 targets) and no after other words (12 distractors). RDI is the number of recalled target words minus the number of recalled distractor words. A higher score reflects a better outcome. | Change from baseline to 6 months |
| Radiation Dose to Spared NPC Region | The mean radiation dose (cGy) to spared NPC region (hippocampus, subventricular zone [SVZ]) in reference to site of lesion. | Day 1 of radiation therapy |
| Volume (cc) of NPC for Sparing Region | The volume of the NPC_for_sparing region as collected using the Pinnacle treatment planning system. | day 1 of radiation therapy |
|
|
NCT02304757
|
99Tc-MDP in Postmenopausal Women With Differentiated Thyroid Cancer and Osteoporosis
|
Postmenopausal women with differentiated thyroid cancer (DTC) taking suppressive doses of levothyroxine (L-T4) are thought to have accelerated bone loss and increased risk of osteoporosis. Therefore, the investigators try to investigate the effects of 99Tc-MDP,alendronate sodium in postmenopausal women with DTC under TSH suppression and osteoporosis.
|
Differentiated thyroid cancer (DTC) has become one of the most common endocrine malignancies. According to American Thyroid Association (ATA) and Chinese Thyroid Association (CTA), most of DTC patients undergo total or near total thyroidectomy, radioiodine ablation and TSH (thyroid stimulating hormone) suppression. Osteoporosis (OS) and fractures are important comorbidities in patients with DTC, with potential negative impact on quality of life (QOL) and survival. The main determinant of skeletal fragility in DTC is the TSH suppression. Postmenopausal women with DTC under TSH suppression therapy are more vulnerable to OS. Technetium-99 methylene diphosphonate (99Tc-MDP) is a decay product of 99mTc-MDP (used for bone scintigraphy) and a novel bisphosphonates, which has been used in China for diseases like rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteochondral lesions of the talus, etc. However, as a member of bisphosphates, little attention has been paid to its anti-OS effect for DTC under TSH suppression.
|
Prospective Trial of 99Tc-MDP and Fosamax in Postmenopausal Women With Differentiated Thyroid Cancer and Osteoporosis Treated With Supraphysiological Doses of Thyroid Hormone
|
Differentiated Thyroid Cancer, Osteoporosis
|
* Drug: 99Tc-MDP
* Drug: Fosamax
|
Inclusion Criteria:~(1) They were pathologically diagnosed with DTC including papillary or follicular carcinoma. (2) They received a near total thyroidectomy and radioiodine treatment. (3) TSH suppression should be at least one year before the study. (4) Bone mineral density (BMD) in lumbar spine and/or hip was tested by Dual-energy X-ray absorptiometry (DXA) at baseline, 6 month (m) and/or 12m follow up. 5) The diagnosis of osteoporosis was T-score ≤-2.5 SD at the lumbar spine, or hip.~Exclusion Criteria:~patients having medications for osteoporosis before TSH suppression treatment;~secondary osteoporosis ;~severe liver or kidney disease;~myelosuppression;~digestive disease;~long term use of immunosuppressive agent, estrogen or estrogen receptor modulators. This study was approved by the Institutional Review Board of Hospital Research Ethics. All the patients were fully acquainted with their treatment and consented to participate in the clinical trial.
|
45 Years
| null |
Female
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients with OS were divided into 99Tc-MDP and fosamax treatment groups.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change of Bone Mineral Density in Lumbar and Hip | Percent change of bone mineral density in lumbar and hip by dual energy x-ray absorptiometry | baseline, 6 months, and 12 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Turnover Markers | bone turnover markers including C-telopeptides of type I collagen (CTX), Type I N-procollagen terminal propeptide(PINP) | baseline and 12 months |
| Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | The health related quality of life was measured by 36-item Short Form Health Status Survey questionnaire (SF-36). The minimum and maximum values were 0 and 100, respectively. Higher scores mean a better a better outcome.~The questionnaire includes 36 items that can be classified into the following eight health status subscales: Physical Functioning, Physical Role Limitations, Bodily Pain, General Health Perception, Vitality, Social Functioning, Emotional Role Limitations, and Mental Health. A standardized Physical Component Summary and a standardized mental component score were calculated. The physical component summary and mental component summary represent the deviation from the reference population in Sweden. Higher scores mean a better a better outcome. | baseline, 6 months, and 12 months |
| Side Effects | A transient rash and phlebitis, gastrointestinal reaction. | 6 months, and 12 months |
|
differentiated thyroid cancer, bone mineral density, thyroid stimulating hormone suppression
|
Alendronate, Methylene diphosphonate, Bone Density Conservation Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 99Tc-MDP<br>15mg 99Tc-MDP were intravenously administered twice a week for 10 weeks, then once a week for 8 weeks, every two weeks for 22 weeks and monthly for another 3m. | Drug: 99Tc-MDP<br>* 99Tc-MDP, H20000218<br>* Other names: Yunke,Technetium [99Tc] Methylenediphosphonate;|
| Active Comparator: Fosamax<br>70mg po every week for 12 months. | Drug: Fosamax<br>* H20080172<br>* Other names: alendronate sodium;|
|
99Tc-MDP in Postmenopausal Women With Differentiated Thyroid Cancer and Osteoporosis
Study Overview
=================
Brief Summary
-----------------
Postmenopausal women with differentiated thyroid cancer (DTC) taking suppressive doses of levothyroxine (L-T4) are thought to have accelerated bone loss and increased risk of osteoporosis. Therefore, the investigators try to investigate the effects of 99Tc-MDP,alendronate sodium in postmenopausal women with DTC under TSH suppression and osteoporosis.
Detailed Description
-----------------
Differentiated thyroid cancer (DTC) has become one of the most common endocrine malignancies. According to American Thyroid Association (ATA) and Chinese Thyroid Association (CTA), most of DTC patients undergo total or near total thyroidectomy, radioiodine ablation and TSH (thyroid stimulating hormone) suppression. Osteoporosis (OS) and fractures are important comorbidities in patients with DTC, with potential negative impact on quality of life (QOL) and survival. The main determinant of skeletal fragility in DTC is the TSH suppression. Postmenopausal women with DTC under TSH suppression therapy are more vulnerable to OS. Technetium-99 methylene diphosphonate (99Tc-MDP) is a decay product of 99mTc-MDP (used for bone scintigraphy) and a novel bisphosphonates, which has been used in China for diseases like rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteochondral lesions of the talus, etc. However, as a member of bisphosphates, little attention has been paid to its anti-OS effect for DTC under TSH suppression.
Official Title
-----------------
Prospective Trial of 99Tc-MDP and Fosamax in Postmenopausal Women With Differentiated Thyroid Cancer and Osteoporosis Treated With Supraphysiological Doses of Thyroid Hormone
Conditions
-----------------
Differentiated Thyroid Cancer, Osteoporosis
Intervention / Treatment
-----------------
* Drug: 99Tc-MDP
* Drug: Fosamax
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: (1) They were pathologically diagnosed with DTC including papillary or follicular carcinoma. (2) They received a near total thyroidectomy and radioiodine treatment. (3) TSH suppression should be at least one year before the study. (4) Bone mineral density (BMD) in lumbar spine and/or hip was tested by Dual-energy X-ray absorptiometry (DXA) at baseline, 6 month (m) and/or 12m follow up. 5) The diagnosis of osteoporosis was T-score ≤-2.5 SD at the lumbar spine, or hip. Exclusion Criteria: patients having medications for osteoporosis before TSH suppression treatment; secondary osteoporosis ; severe liver or kidney disease; myelosuppression; digestive disease; long term use of immunosuppressive agent, estrogen or estrogen receptor modulators. This study was approved by the Institutional Review Board of Hospital Research Ethics. All the patients were fully acquainted with their treatment and consented to participate in the clinical trial.
Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients with OS were divided into 99Tc-MDP and fosamax treatment groups.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 99Tc-MDP<br>15mg 99Tc-MDP were intravenously administered twice a week for 10 weeks, then once a week for 8 weeks, every two weeks for 22 weeks and monthly for another 3m. | Drug: 99Tc-MDP<br>* 99Tc-MDP, H20000218<br>* Other names: Yunke,Technetium [99Tc] Methylenediphosphonate;|
| Active Comparator: Fosamax<br>70mg po every week for 12 months. | Drug: Fosamax<br>* H20080172<br>* Other names: alendronate sodium;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change of Bone Mineral Density in Lumbar and Hip | Percent change of bone mineral density in lumbar and hip by dual energy x-ray absorptiometry | baseline, 6 months, and 12 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Turnover Markers | bone turnover markers including C-telopeptides of type I collagen (CTX), Type I N-procollagen terminal propeptide(PINP) | baseline and 12 months |
| Health Related Quality of Life by 36-item Short Form Health Status Survey Questionnaire (0-100) | The health related quality of life was measured by 36-item Short Form Health Status Survey questionnaire (SF-36). The minimum and maximum values were 0 and 100, respectively. Higher scores mean a better a better outcome. The questionnaire includes 36 items that can be classified into the following eight health status subscales: Physical Functioning, Physical Role Limitations, Bodily Pain, General Health Perception, Vitality, Social Functioning, Emotional Role Limitations, and Mental Health. A standardized Physical Component Summary and a standardized mental component score were calculated. The physical component summary and mental component summary represent the deviation from the reference population in Sweden. Higher scores mean a better a better outcome. | baseline, 6 months, and 12 months |
| Side Effects | A transient rash and phlebitis, gastrointestinal reaction. | 6 months, and 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
differentiated thyroid cancer, bone mineral density, thyroid stimulating hormone suppression
|
NCT03151200
|
Visual Functional Connectivity and Visual Improvement After TMS/Binocular Treatment
|
The purpose of this study is to assess the effectiveness of combining binocular treatment with repetitive transcranial magnetic stimulation (rTMS) in improving the vision of adults with amblyopia. This study also seeks to assess the effect of this combined treatment on cortical neural function and functional connectivity.
|
Prior to the study, ocular misalignment and refraction abnormalities will be corrected This correction is part of standard patient care rather than a procedural component of the current study.~Procedure Participants will undergo one hour structural and functional MRI prior to their treatment. We will perform an interim analysis of the fMRI results once five amblyopic patients have completed the fMRI study. If the data shows significant differences in the resting state visual network in amblyopia patients compared to the existing normal visual resting state, we will pursue the fMRI study with the remaining 15 participants. Misalignment of the eyes will be corrected prior to a patients' participation by using prisms (if medically indicated). This correction is part of standard patient care rather than a procedural component of the current study. Participants will be randomly appointed to initially be in either the sham or the treatment group (10 patients in each group). All patients will receive five days of one hour visual binocular training by playing a specially designed falling blocks videogame on a computer screen that will be individually calibrated for each person. Group one will receive 18 minutes of rTMS at the beginning of their visual training every day for 5 days. Group two will receive 18 minutes of TMS followed by sham visual training every day for 5 days. At the end of five days, participants will switch groups. Participants will be blind as to whether they receive sham or real binocular treatment on each occasion.~A sensorimotor visual profile, including visual acuity, suppression, stereovision, binocularity, contrast sensitivity and eye alignment, will be completed for each patient at baseline, after five sessions, and at the end of the treatment. This profile will be completed using the PVVAT system, Worth-4-Dot test, Randot stereovision test, anaglyphic dichoptic coherence motion threshold with red-green glasses (using Psykinematix vision system), cross cover test with prism bars. fMRI will be repeated post-treatment only for individuals who showed abnormal fMRI at baseline. This second scan will investigate whether the treatment affected and normalized the resting state visual network.~Functional MRI:~All scanning will be performed on a 3.0 T Siemens Tim Trio scanner equipped with a 12-channel head coil. Scanning will take place on up to three visits: Pre-treatment (retinotopic mapping), and two post treatment scans.~Pre-treatment: structural, resting state and BOLD functional MRI (fMRI) data will be acquired. Participants will complete a structural MRI scan at the beginning of each MRI session. This is a high-resolution 3-dimensional image of the whole brain (Imaging parameters: MPRAGE, 1mm thick slices, zero spacing between slices, TR = 1900 ms, TE = 2.2 ms, in plane resolution of 0.94 x 0.94, 256 x 256 matrix size with a 24 cm field of view, 176 volumes, resulting in a 8 minute 6 second scan time.~After the high-resolution image has been acquired, the resting state functional MRI data will be acquired with the following parameters: Siemens echo planar imaging (EPI) sequence, 3 mm thick slices, zero spacing between slices, repetition time of 3000 ms, echo time of 30 ms, flip angle of 90°, 64 x 64 matrix size, 24 cm field of view, 140 volumes, resulting in a 7 minute 9 second scan time. During this session the patients will close their eyes and rest.~Following the resting state fMRI session we will perform task-based and retinotopic mapping using standard wedge and ring protocols to evoke blood oxygen level-depended (BOLD) response in the visual cortex. (Li X, Dumoulin SO, Mansouri B, Hess RF. The fidelity of the cortical retinotopic map in human amblyopia. Eur J Neurosci. 2007;25:1265-1277.29). Functional data will be acquired using a T2-weighted gradient echo EPI sequence (retinotopic mapping, TR = 1200 ms, TE = 30 ms, flip angle = 65°, voxel resolution 2.5 x 2.5 x 2.5 mm; post treatment scans, TR = 2000 ms, TE = 30 ms, flip angle = 90°, voxel resolution = 3.0 x 3.0 x 3.0 mm). Stimuli will be presented monocularly and each eye will be mapped separately. Borders of retinotopic areas and corresponding regions of interest will be defined using an averaged map of the left and right eye in each participant. During fMRI, participants will be presented with visual stimuli (viewed over an MRI compatible white screen through a coil-mounted mirror) and perform a reaction time task where they will simply press a button when they detect a change in the fixation point. The task will be unrelated to the stimuli used.~The subsequent fMRI scanning sessions will be performed after two week of Transcranial Magnetic stimulation (TMS) and binocular treatment, which will assess the effect of rTMS plus sham/real binocular treatment on the response of the visual cortex to inputs from the amblyopic versus fellow fixing eye. We will use the localizing information from the first session. The resting state and task-based fMRI will be repeated.~1. Pre -treatment visit:~a. Localizer to find slice plan (1-2 min) b. MPRAGE anatomical (7-10 min) c. Resting state - eyes closed stay awake (7-10 min) d. Retinotopic mapping (48 min PLUS time to alternate eye patch between runs) i. 4 scans of block design amblyopic eye covered~2 eccentricity,~2 polar angle,~2 clockwise,~2 counterclockwise, ii. 4 scans of block design fellow fixing eye covered~One week of either Group A) rTMS and true binocular treatment or Group B) rTMS and sham binocular treatment 2. Post treatment visit:~Localizer (1-2 min)~MPRAGE anatomical (7-10 min)~Resting state - eyes closed stay awake (~not retinotopic mapping~fMRI block design~i. checkerboard stimulus 4 scans per session per eye One week of CROSS OVER treatment Group A) rTMS and sham binocular treatment or Group B) rTMS and binocular treatment fMRI analysis Resting state fMRI data will be pre-processed to reduce artifacts and noise-related signal components. Following pre-processing, data will be analyzed at the individual level using Independent Component Analysis. The individually analyzed data will then be standardized to stereotactic space using a Talairach atlas. The standardized data will be run through a Self-Organized Grouped ICA which will summarize the ICA data from all participants. An analysis of variance will be used to assess differences in functional connectivity in brain regions between the groups (pre- and post-rTMS treatment).~Potential harms and benefits It is our hope that as a result of their participation in this study, patients will see an improvement in many aspects of their vision, including overall visual acuity and contrast sensitivity.~There is a chance that improving vision in the weak eye may result in double vision if the position of the eyes (alignment) is suboptimal. This double vision may spontaneously subside over time as the training effect wears off (in the absence of further training). If double vision persists, participants may have to be referred to neurology, optometry or ophthalmology clinics for symptom management. Patching over the weak eye may be required in order to eliminate the double vision, decreasing vision in the weak eye in an effort to returning vision to what it was before participation in the study. Other treatments for double vision include optical correction with glasses that contain prisms or surgical intervention to align the two eyes. The latter methods help fuse images from the two eyes in most of cases.~The rTMS procedures proposed for this study are well within recommended safety guidelines, so the risk of adverse events is slim. TMS can cause twitching of the scalp or face muscles during stimulation, which may be uncomfortable. About 1 out of 10 subjects report a headache after the TMS measurement, which is usually mild and transient. If needed, the headache can be treated with mild over-the-counter pain medicine, such as acetaminophen/Tylenol. The risk of seizure from rTMS is elevated in individuals with a history of epilepsy or a family history of seizures, which is why these conditions are exclusion criteria for this study.
|
Visual Functional Connectivity and Visual Function in Amblyopia Before and After TMS and/or Binocular Treatment
|
Amblyopia
|
* Device: Computer based binocular treatment
* Device: Transcranial magnetic stimulation
|
Inclusion Criteria:~A total of 20 strabismic or mixed amblyopic adult patients (eighteen or older) will be recruited from Dr. Mansouri's practice. Patients will be asked for their permission to be contacted by a research assistant with regard to the study. A research assistant will then contact patients and inform them about the study, its procedures, and its voluntary nature. Patients will not be contacted without their previous permission.~Exclusion Criteria:~Given the use of rTMS and MRI in this study, participants will be excluded if they have any contraindications to these procedures. Contraindications include: the presence of metal clips or implants in the body (such as pacemakers, defibrillators or neural stimulators), metallic dental work, severe claustrophobia, epilepsy, a family history of seizures, or the taking of epileptogenic medications. Pregnant individuals will also be excluded as a precaution.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of visual acuity in amblyopic eyes after TMS/binocular treatment | | 2 weeks treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of stereovision and reduction in suppression in amblyopic patients after TMS/binocular treatment | | 2 weeks treatment |
|
Amblyopia treatment
|
Amblyopia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vision Disorders, Sensation Disorders, Neurologic Manifestations, Eye Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: binocular treatment<br>Active treatment group will receive five days of one hour visual binocular training by playing a specifically designed falling blocks video game on a computer screen that will be individually calibrated for each person with red-green glasses with treatment effect. | Device: Computer based binocular treatment<br>* Binocular amblyopia treatment involves presenting stimuli over a computer screen to the amblyopic eye those are at higher contrast compared to the stimuli that are presented to the good eye, which balances the performances of the two eyes and over time improves the amblyopic eye vision.<br>Device: Transcranial magnetic stimulation<br>* TMS is a non-invasive research method that generates electrical current at the cortex that can excite neuronal activities and neuronal plasticity.<br>* Other names: TMS;|
| Sham Comparator: sham treatment<br>Sham treatment group will receive five days of one hour sham visual binocular training by playing a specially designed falling blocks video game on a computer screen with polarized glasses with no treatment effect. | Device: Transcranial magnetic stimulation<br>* TMS is a non-invasive research method that generates electrical current at the cortex that can excite neuronal activities and neuronal plasticity.<br>* Other names: TMS;|
|
Visual Functional Connectivity and Visual Improvement After TMS/Binocular Treatment
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the effectiveness of combining binocular treatment with repetitive transcranial magnetic stimulation (rTMS) in improving the vision of adults with amblyopia. This study also seeks to assess the effect of this combined treatment on cortical neural function and functional connectivity.
Detailed Description
-----------------
Prior to the study, ocular misalignment and refraction abnormalities will be corrected This correction is part of standard patient care rather than a procedural component of the current study. Procedure Participants will undergo one hour structural and functional MRI prior to their treatment. We will perform an interim analysis of the fMRI results once five amblyopic patients have completed the fMRI study. If the data shows significant differences in the resting state visual network in amblyopia patients compared to the existing normal visual resting state, we will pursue the fMRI study with the remaining 15 participants. Misalignment of the eyes will be corrected prior to a patients' participation by using prisms (if medically indicated). This correction is part of standard patient care rather than a procedural component of the current study. Participants will be randomly appointed to initially be in either the sham or the treatment group (10 patients in each group). All patients will receive five days of one hour visual binocular training by playing a specially designed falling blocks videogame on a computer screen that will be individually calibrated for each person. Group one will receive 18 minutes of rTMS at the beginning of their visual training every day for 5 days. Group two will receive 18 minutes of TMS followed by sham visual training every day for 5 days. At the end of five days, participants will switch groups. Participants will be blind as to whether they receive sham or real binocular treatment on each occasion. A sensorimotor visual profile, including visual acuity, suppression, stereovision, binocularity, contrast sensitivity and eye alignment, will be completed for each patient at baseline, after five sessions, and at the end of the treatment. This profile will be completed using the PVVAT system, Worth-4-Dot test, Randot stereovision test, anaglyphic dichoptic coherence motion threshold with red-green glasses (using Psykinematix vision system), cross cover test with prism bars. fMRI will be repeated post-treatment only for individuals who showed abnormal fMRI at baseline. This second scan will investigate whether the treatment affected and normalized the resting state visual network. Functional MRI: All scanning will be performed on a 3.0 T Siemens Tim Trio scanner equipped with a 12-channel head coil. Scanning will take place on up to three visits: Pre-treatment (retinotopic mapping), and two post treatment scans. Pre-treatment: structural, resting state and BOLD functional MRI (fMRI) data will be acquired. Participants will complete a structural MRI scan at the beginning of each MRI session. This is a high-resolution 3-dimensional image of the whole brain (Imaging parameters: MPRAGE, 1mm thick slices, zero spacing between slices, TR = 1900 ms, TE = 2.2 ms, in plane resolution of 0.94 x 0.94, 256 x 256 matrix size with a 24 cm field of view, 176 volumes, resulting in a 8 minute 6 second scan time. After the high-resolution image has been acquired, the resting state functional MRI data will be acquired with the following parameters: Siemens echo planar imaging (EPI) sequence, 3 mm thick slices, zero spacing between slices, repetition time of 3000 ms, echo time of 30 ms, flip angle of 90°, 64 x 64 matrix size, 24 cm field of view, 140 volumes, resulting in a 7 minute 9 second scan time. During this session the patients will close their eyes and rest. Following the resting state fMRI session we will perform task-based and retinotopic mapping using standard wedge and ring protocols to evoke blood oxygen level-depended (BOLD) response in the visual cortex. (Li X, Dumoulin SO, Mansouri B, Hess RF. The fidelity of the cortical retinotopic map in human amblyopia. Eur J Neurosci. 2007;25:1265-1277.29). Functional data will be acquired using a T2-weighted gradient echo EPI sequence (retinotopic mapping, TR = 1200 ms, TE = 30 ms, flip angle = 65°, voxel resolution 2.5 x 2.5 x 2.5 mm; post treatment scans, TR = 2000 ms, TE = 30 ms, flip angle = 90°, voxel resolution = 3.0 x 3.0 x 3.0 mm). Stimuli will be presented monocularly and each eye will be mapped separately. Borders of retinotopic areas and corresponding regions of interest will be defined using an averaged map of the left and right eye in each participant. During fMRI, participants will be presented with visual stimuli (viewed over an MRI compatible white screen through a coil-mounted mirror) and perform a reaction time task where they will simply press a button when they detect a change in the fixation point. The task will be unrelated to the stimuli used. The subsequent fMRI scanning sessions will be performed after two week of Transcranial Magnetic stimulation (TMS) and binocular treatment, which will assess the effect of rTMS plus sham/real binocular treatment on the response of the visual cortex to inputs from the amblyopic versus fellow fixing eye. We will use the localizing information from the first session. The resting state and task-based fMRI will be repeated. 1. Pre -treatment visit: a. Localizer to find slice plan (1-2 min) b. MPRAGE anatomical (7-10 min) c. Resting state - eyes closed stay awake (7-10 min) d. Retinotopic mapping (48 min PLUS time to alternate eye patch between runs) i. 4 scans of block design amblyopic eye covered 2 eccentricity, 2 polar angle, 2 clockwise, 2 counterclockwise, ii. 4 scans of block design fellow fixing eye covered One week of either Group A) rTMS and true binocular treatment or Group B) rTMS and sham binocular treatment 2. Post treatment visit: Localizer (1-2 min) MPRAGE anatomical (7-10 min) Resting state - eyes closed stay awake ( not retinotopic mapping fMRI block design i. checkerboard stimulus 4 scans per session per eye One week of CROSS OVER treatment Group A) rTMS and sham binocular treatment or Group B) rTMS and binocular treatment fMRI analysis Resting state fMRI data will be pre-processed to reduce artifacts and noise-related signal components. Following pre-processing, data will be analyzed at the individual level using Independent Component Analysis. The individually analyzed data will then be standardized to stereotactic space using a Talairach atlas. The standardized data will be run through a Self-Organized Grouped ICA which will summarize the ICA data from all participants. An analysis of variance will be used to assess differences in functional connectivity in brain regions between the groups (pre- and post-rTMS treatment). Potential harms and benefits It is our hope that as a result of their participation in this study, patients will see an improvement in many aspects of their vision, including overall visual acuity and contrast sensitivity. There is a chance that improving vision in the weak eye may result in double vision if the position of the eyes (alignment) is suboptimal. This double vision may spontaneously subside over time as the training effect wears off (in the absence of further training). If double vision persists, participants may have to be referred to neurology, optometry or ophthalmology clinics for symptom management. Patching over the weak eye may be required in order to eliminate the double vision, decreasing vision in the weak eye in an effort to returning vision to what it was before participation in the study. Other treatments for double vision include optical correction with glasses that contain prisms or surgical intervention to align the two eyes. The latter methods help fuse images from the two eyes in most of cases. The rTMS procedures proposed for this study are well within recommended safety guidelines, so the risk of adverse events is slim. TMS can cause twitching of the scalp or face muscles during stimulation, which may be uncomfortable. About 1 out of 10 subjects report a headache after the TMS measurement, which is usually mild and transient. If needed, the headache can be treated with mild over-the-counter pain medicine, such as acetaminophen/Tylenol. The risk of seizure from rTMS is elevated in individuals with a history of epilepsy or a family history of seizures, which is why these conditions are exclusion criteria for this study.
Official Title
-----------------
Visual Functional Connectivity and Visual Function in Amblyopia Before and After TMS and/or Binocular Treatment
Conditions
-----------------
Amblyopia
Intervention / Treatment
-----------------
* Device: Computer based binocular treatment
* Device: Transcranial magnetic stimulation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A total of 20 strabismic or mixed amblyopic adult patients (eighteen or older) will be recruited from Dr. Mansouri's practice. Patients will be asked for their permission to be contacted by a research assistant with regard to the study. A research assistant will then contact patients and inform them about the study, its procedures, and its voluntary nature. Patients will not be contacted without their previous permission. Exclusion Criteria: Given the use of rTMS and MRI in this study, participants will be excluded if they have any contraindications to these procedures. Contraindications include: the presence of metal clips or implants in the body (such as pacemakers, defibrillators or neural stimulators), metallic dental work, severe claustrophobia, epilepsy, a family history of seizures, or the taking of epileptogenic medications. Pregnant individuals will also be excluded as a precaution.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: binocular treatment<br>Active treatment group will receive five days of one hour visual binocular training by playing a specifically designed falling blocks video game on a computer screen that will be individually calibrated for each person with red-green glasses with treatment effect. | Device: Computer based binocular treatment<br>* Binocular amblyopia treatment involves presenting stimuli over a computer screen to the amblyopic eye those are at higher contrast compared to the stimuli that are presented to the good eye, which balances the performances of the two eyes and over time improves the amblyopic eye vision.<br>Device: Transcranial magnetic stimulation<br>* TMS is a non-invasive research method that generates electrical current at the cortex that can excite neuronal activities and neuronal plasticity.<br>* Other names: TMS;|
| Sham Comparator: sham treatment<br>Sham treatment group will receive five days of one hour sham visual binocular training by playing a specially designed falling blocks video game on a computer screen with polarized glasses with no treatment effect. | Device: Transcranial magnetic stimulation<br>* TMS is a non-invasive research method that generates electrical current at the cortex that can excite neuronal activities and neuronal plasticity.<br>* Other names: TMS;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of visual acuity in amblyopic eyes after TMS/binocular treatment | | 2 weeks treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of stereovision and reduction in suppression in amblyopic patients after TMS/binocular treatment | | 2 weeks treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Amblyopia treatment
|
NCT05603052
|
A Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older
|
A phase III, randomized, observer-blind, active-controlled, parallel-group, multi-center study to evaluate immunogenicity and safety of a preventive COVID-19 vaccine EuCorVac-19 in healthy adults aged 18 years and older
|
A Phase III, Randomized, Observer-blind, Active-controlled, Parallel-group, Multi-center Study to Evaluate Immunogenicity and Safety of a Preventive COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older
|
COVID-19
|
* Biological: EuCorVac-19
* Biological: ChAdOx1 nCoV-19
|
Inclusion Criteria:~Individuals aged 18 years and older who voluntarily decide to participate in this study and provide written informed consent~Female of childbearing potential who agree to use medically allowed methods of contraception during the study period~Individuals who agrees not to perform blood donation and transfusion during the study period~Exclusion Criteria:~Individual being considered to be confirmed COVID-19~Direct contact with COVID-19 infected person within 14 days prior to the 1st dose of the IP~Individuals at high risk of exposure to SARS-CoV-2~Individuals with clinically significant abnormalities in clinical laboratory tests, ECGs, and chest X-ray during screening~Individuals with fever within 72 hours prior to the 1st dose of the IP or suspected other infectious disease or symptoms associated with other infectious disease~Individuals with serious medical or psychiatric disease~History of SARS-CoV or MERS-CoV infection~History of allergic reaction or hypersensitivity reactions to any of components of the IP~History of serious adverse events, serious allergic reaction or serious hypersensitivity reactions to vaccination~History of receiving organ or bone marrow transplant~Suspected or history of drug abuse or alcohol abuse within 6 months prior to vaccination~History of vaccination against SARS-CoV, MERS-CoV, or SARS-CoV-2~History of vaccination with test vaccine substance~Treatment with immunosuppressants or immune modifying drugs~History of treatment with antipsychotics or opioid dependence~Pregnant or lactating women~Other reasons based on which the individual is considered to be ineligible for this study in the opinion of the investigator
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of GMT of neutralizing antibody of EuCorVac-19 and ChAdOx1 | | 14 days after the 2nd vaccination |
| The difference in neutralizing antibody SRR of EuCorVac-19 and ChAdOx1 | | 14 days after the 2nd vaccination |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of solicited Adverse Events (AEs) | | Through 7 days after each vaccination |
| Occurrence of unsolicited Adverse Events (AEs) | | Through 28 days after the 2nd vaccination |
|
COVID-19, Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Infections, Virus Diseases, Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group(EuCorVac-19) - Cohort A<br>Cohort A - Immunogenicity cohort | Biological: EuCorVac-19<br>* COVID-19 vaccine<br>|
| Active Comparator: Comparator group(ChAdOx1) - Cohort A<br>Cohort A - Immunogenicity cohort | Biological: ChAdOx1 nCoV-19<br>* COVID-19 vaccine<br>* Other names: COVISHIELD;|
| Experimental: Test group(EuCorVac-19) - Cohort B<br>Cohort B - Safety cohort | Biological: EuCorVac-19<br>* COVID-19 vaccine<br>|
| Active Comparator: Comparator group(ChAdOx1) - Cohort B<br>Cohort B - Safety cohort | Biological: ChAdOx1 nCoV-19<br>* COVID-19 vaccine<br>* Other names: COVISHIELD;|
|
A Phase III of COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older
Study Overview
=================
Brief Summary
-----------------
A phase III, randomized, observer-blind, active-controlled, parallel-group, multi-center study to evaluate immunogenicity and safety of a preventive COVID-19 vaccine EuCorVac-19 in healthy adults aged 18 years and older
Official Title
-----------------
A Phase III, Randomized, Observer-blind, Active-controlled, Parallel-group, Multi-center Study to Evaluate Immunogenicity and Safety of a Preventive COVID-19 Vaccine EuCorVac-19 in Healthy Adults Aged 18 Years and Older
Conditions
-----------------
COVID-19
Intervention / Treatment
-----------------
* Biological: EuCorVac-19
* Biological: ChAdOx1 nCoV-19
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Individuals aged 18 years and older who voluntarily decide to participate in this study and provide written informed consent Female of childbearing potential who agree to use medically allowed methods of contraception during the study period Individuals who agrees not to perform blood donation and transfusion during the study period Exclusion Criteria: Individual being considered to be confirmed COVID-19 Direct contact with COVID-19 infected person within 14 days prior to the 1st dose of the IP Individuals at high risk of exposure to SARS-CoV-2 Individuals with clinically significant abnormalities in clinical laboratory tests, ECGs, and chest X-ray during screening Individuals with fever within 72 hours prior to the 1st dose of the IP or suspected other infectious disease or symptoms associated with other infectious disease Individuals with serious medical or psychiatric disease History of SARS-CoV or MERS-CoV infection History of allergic reaction or hypersensitivity reactions to any of components of the IP History of serious adverse events, serious allergic reaction or serious hypersensitivity reactions to vaccination History of receiving organ or bone marrow transplant Suspected or history of drug abuse or alcohol abuse within 6 months prior to vaccination History of vaccination against SARS-CoV, MERS-CoV, or SARS-CoV-2 History of vaccination with test vaccine substance Treatment with immunosuppressants or immune modifying drugs History of treatment with antipsychotics or opioid dependence Pregnant or lactating women Other reasons based on which the individual is considered to be ineligible for this study in the opinion of the investigator
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group(EuCorVac-19) - Cohort A<br>Cohort A - Immunogenicity cohort | Biological: EuCorVac-19<br>* COVID-19 vaccine<br>|
| Active Comparator: Comparator group(ChAdOx1) - Cohort A<br>Cohort A - Immunogenicity cohort | Biological: ChAdOx1 nCoV-19<br>* COVID-19 vaccine<br>* Other names: COVISHIELD;|
| Experimental: Test group(EuCorVac-19) - Cohort B<br>Cohort B - Safety cohort | Biological: EuCorVac-19<br>* COVID-19 vaccine<br>|
| Active Comparator: Comparator group(ChAdOx1) - Cohort B<br>Cohort B - Safety cohort | Biological: ChAdOx1 nCoV-19<br>* COVID-19 vaccine<br>* Other names: COVISHIELD;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of GMT of neutralizing antibody of EuCorVac-19 and ChAdOx1 | | 14 days after the 2nd vaccination |
| The difference in neutralizing antibody SRR of EuCorVac-19 and ChAdOx1 | | 14 days after the 2nd vaccination |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of solicited Adverse Events (AEs) | | Through 7 days after each vaccination |
| Occurrence of unsolicited Adverse Events (AEs) | | Through 28 days after the 2nd vaccination |
|
||
NCT02052986
|
An Open-Label Study of Vascazen in Cardiac Rehab Patients With Deficient Blood Omega-3 Fatty Acid Levels
|
The investigators aim to test the hypothesis that dietary supplementation with VASCAZEN will correct omega-3 deficiency in cardiac rehab patients and improve biochemical risk factors.
| null |
Dyslipidemia
|
* Other: VASCAZEN
|
Inclusion Criteria:~Adult subjects (> or = 18 years of age)~Enrolled in Cardiac Rehabilitation clinic with documented cardiovascular disease as assessed by the principle investigator~Has had cardiovascular examination within the past 2 months~Exclusion Criteria:~Subjects who refuse to provide written consent~Subjects with medical conditions, as determined by the principal investigator, which prevented them from study participation~Subjects with a known bleeding or clotting disorder~Subjects with known allergies to fish~Subjects with an implantable cardiac defibrillator~Subjects with a heart transplant~Female subjects who are currently taking hormone replacement therapy~Subjects who are pregnant or planning on becoming pregnant~Subjects currently taking Omega-3 fatty acid supplements (either under medical supervision or self-administered)
|
18 Years
| null |
All
|
No
|
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in sum of Omega-Score and Omega-Index | Change in the sum of the subject's blood Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA) + Docosapentaenoic acid (DPA) levels (Omega-Score) and the change in the sum of the subject's red blood cell (RBC) EPA + DHA levels (Omega-Index) over 12 weeks of study treatment with Vascazen | 12 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patient health questionnaire-9 (PHQ-9) depression scale | Change in patient health questionnaire-9 (PHQ-9) depression scale after 12 weeks of study treatment | 12 weeks |
|
Fatty Acids, Omega-3, Omega-3 fatty acids, Docosahexaenoic acid (DHA), Eicosapentaenoic acid (EPA), Docosapentaenoic acid (DPA), Omega Index, Omega Score, Cardiac Rehab
|
Dyslipidemias, Lipid Metabolism Disorders, Metabolic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vascazen<br>Enrolled patients will receive four capsules daily of VASCAZEN (a 3.0 gram daily dose of EPA+DHA) for a total of 12 weeks. | Other: VASCAZEN<br>* All enrolled subjects will receive 4 capsules daily of VASCAZEN which delivers 3.0 grams of EPA and DHA<br>|
|
An Open-Label Study of Vascazen in Cardiac Rehab Patients With Deficient Blood Omega-3 Fatty Acid Levels
Study Overview
=================
Brief Summary
-----------------
The investigators aim to test the hypothesis that dietary supplementation with VASCAZEN will correct omega-3 deficiency in cardiac rehab patients and improve biochemical risk factors.
Conditions
-----------------
Dyslipidemia
Intervention / Treatment
-----------------
* Other: VASCAZEN
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult subjects (> or = 18 years of age) Enrolled in Cardiac Rehabilitation clinic with documented cardiovascular disease as assessed by the principle investigator Has had cardiovascular examination within the past 2 months Exclusion Criteria: Subjects who refuse to provide written consent Subjects with medical conditions, as determined by the principal investigator, which prevented them from study participation Subjects with a known bleeding or clotting disorder Subjects with known allergies to fish Subjects with an implantable cardiac defibrillator Subjects with a heart transplant Female subjects who are currently taking hormone replacement therapy Subjects who are pregnant or planning on becoming pregnant Subjects currently taking Omega-3 fatty acid supplements (either under medical supervision or self-administered)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vascazen<br>Enrolled patients will receive four capsules daily of VASCAZEN (a 3.0 gram daily dose of EPA+DHA) for a total of 12 weeks. | Other: VASCAZEN<br>* All enrolled subjects will receive 4 capsules daily of VASCAZEN which delivers 3.0 grams of EPA and DHA<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in sum of Omega-Score and Omega-Index | Change in the sum of the subject's blood Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA) + Docosapentaenoic acid (DPA) levels (Omega-Score) and the change in the sum of the subject's red blood cell (RBC) EPA + DHA levels (Omega-Index) over 12 weeks of study treatment with Vascazen | 12 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patient health questionnaire-9 (PHQ-9) depression scale | Change in patient health questionnaire-9 (PHQ-9) depression scale after 12 weeks of study treatment | 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fatty Acids, Omega-3, Omega-3 fatty acids, Docosahexaenoic acid (DHA), Eicosapentaenoic acid (EPA), Docosapentaenoic acid (DPA), Omega Index, Omega Score, Cardiac Rehab
|
|
NCT01772719
|
Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid
|
The purpose of this study is to examine the effect of simvastatin and zoledronic acid on M-protein and/or free light chains when added to conventional chemotherapy for the treatment of multiple myeloma patients.
|
We hypothesize that the addition of simvastatin and zoledronic acid to bortezomib, thalidomide, melphalan or dexamethasone based regimens will decrease drug resistance when treating refractory multiple myeloma. We hypothesize that the addition of simvastatin and zoledronic acid will not increase the chemotherapy toxicity significantly and will be tolerable for patients. We believe simvastatin and zoledronic acid have antitumor properties and will contribute to reversal of resistance. Treatment will be significantly enhanced when these agents are combined
|
Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid
|
Multiple Myeloma
|
* Drug: Simvastatin and zoledronic acid
|
Inclusion Criteria:~have a definitive diagnosis of Multiple Myeloma (using the International Myeloma Working Group Guidelines).~meet one of the following two requirements:~Have achieved minimal response (MR) or stable disease (SD) in current treatment regimen after a minimum of two cycles.~Have partial response but show no further improvement in paraprotein levels in the latest two measurements.~must have measurable active or symptomatic disease. Measurable disease may be paraprotein or free light chains in serum or urine, or the presence of bone marrow plasma cells, defined by one or more of the following criteria:~Presence of serum M-protein concentration > 1g/dL.~Urine M-protein excretion > 200mg in 24-hour urine collection.~Serum free light chain concentration ≥ 10mg/dL and abnormal kappa/lambda ratio.~Urine free light chain concentration ≥ 100mg/L and abnormal kappa/lambda ratio.~Bone marrow plasma cell percentage ≥ 30% (if no detectable M-protein or FLC.)~Age > 18 years of age.~If female with reproductive capacity: on effective means of birth control during the entire duration of the treatment.~Patients must have recovered from acute toxicities resulting from therapy administered prior to entering this study to grade 1 or less (CTCAE 4) Alopecia may not be resolved.~Ability to understand and willingness to sign a written informed consent document.~Life expectancy of greater than 8 weeks.~ECOG performance status 0, 1, or 2 (Karnofsky > 60%; see Appendix A).~have adequate bone marrow function as defined below:~absolute neutrophil count > 500/ul~platelets > 30,000/ul~have adequate liver function as defined below:~total bilirubin < 2 times the upper limit of normal~AST(SGOT), ALT(SGPT) < 3 x upper limit of normal~have adequate renal function as defined by a creatinine clearance > 40 mL/min (measured or estimated by the Cockcroft-Gault formula).~have no signs of significant rhabdomyolysis determined by CPK levels with a CK < 5 times the upper limit of normal.~Exclusion Criteria:~have not received any chemotherapy treatment for multiple myeloma prior to being enrolled in the study.~show progressive disease or are not tolerating current chemotherapy regimen.~were receiving simvastatin (dose > 40mg/day) while receiving current chemotherapy regimen for multiple myeloma.~failed or progressed on more than two chemotherapy regimens, including current treatment; prior to enrolling in this study.~receiving any other investigational agent(s).~Active second malignancy in the last 5 years except for non-melanoma skin cancer or carcinoma-in-situ.~Pregnant women are ineligible, as treatment involves unforeseeable risks to the embryo or fetus. Female patients with reproductive capacity are required to use effective means of birth control during the entire duration of the treatment.~History of hypersensitivity reactions attributed to simvastatin or zoledronic acid.~receiving medications that may increase risk of rhabdomyolysis such as itraconazole, ketoconazole, erythromycin, cyclosporine, amiodarone, verapamil, clarithromycin, nefazodone, ranolazine, HIV protease inhibitors, gemfibrozil, posaconazole, danazol, amiodarone, diltiazem and amlodipine.~Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myopathy, untreated hypothyroidism, hereditary myopathy in the family history, unstable angina pectoris, liver disease not due to multiple myeloma, cardiac arrhythmia that is symptomatic or not rate controlled, active connective tissue disease, active autoimmune disease, or psychiatric illness/social situations that would limit compliance with study requirements.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Paraprotein Level and Free Light Chain (FLC) Ratio From Baseline Measurement | The effect of simvastatin and zolendronic acid on M-Protein and FLC ratio will be measured 4 weeks after treatment begins, then every 4 weeks until progression of disease. | 4 weeks after treatment begins |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | OS(Overall survival) is measured from date of study enrollment until death. | At start of year 2 of follow-up on all surviving participants |
| Duration of Response | Response will be accessed by one of the study investigators at each monthly follow up visit during year one. | Year 1 follow up visits occur monthly |
| Progression Free Survival (PFS) | Study will estimate PFS when there is one year of follow up data for all surviving participants | At start of year 2 follow up on all surviving participants |
| Duration of Response | Response will be assessed by one of the study investigators at each three month follow up visit for Year 2 | Year 2 follow up visit occur every three months |
| Duration of Response | Response will be assessed by one of the study investigators at each six month follow up visit for Year 3-5 | Year 3-5 follow up visit occurs every six months |
| Incidence Rate of Toxicity | Descriptive statistics will be provided regarding incidence rates of toxicity. Patients will be monitored for safety throughout the study. | Every 12 months up to one month after treatment completion |
| Comparison of Quality of Life Scores | The QOL scores taken at the start of the study and every 4 months after treatment starts will be analyzed using Wilcoxon test for paired differences | Up to 2 months after last treatment has been completed |
|
refractory multiple myeloma
|
Zoledronic Acid, Simvastatin, Anticholesteremic Agents, Hypolipidemic Agents, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Lipid Regulating Agents, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Enzyme Inhibitors, Bone Density Conservation Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Arm<br>Study Arm | Drug: Simvastatin and zoledronic acid<br>* Simvastatin 80 mg PO daily starting two days before starting chemotherapy and stopping two days after chemotherapy.~Zoledronic acid 4 mg IV over 15 minutes on day 1 and then monthly.<br>* Other names: Zocor;|
|
Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine the effect of simvastatin and zoledronic acid on M-protein and/or free light chains when added to conventional chemotherapy for the treatment of multiple myeloma patients.
Detailed Description
-----------------
We hypothesize that the addition of simvastatin and zoledronic acid to bortezomib, thalidomide, melphalan or dexamethasone based regimens will decrease drug resistance when treating refractory multiple myeloma. We hypothesize that the addition of simvastatin and zoledronic acid will not increase the chemotherapy toxicity significantly and will be tolerable for patients. We believe simvastatin and zoledronic acid have antitumor properties and will contribute to reversal of resistance. Treatment will be significantly enhanced when these agents are combined
Official Title
-----------------
Overcoming Chemotherapy Resistance In Refractory Multiple Myeloma With Simvastatin and Zoledronic Acid
Conditions
-----------------
Multiple Myeloma
Intervention / Treatment
-----------------
* Drug: Simvastatin and zoledronic acid
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: have a definitive diagnosis of Multiple Myeloma (using the International Myeloma Working Group Guidelines). meet one of the following two requirements: Have achieved minimal response (MR) or stable disease (SD) in current treatment regimen after a minimum of two cycles. Have partial response but show no further improvement in paraprotein levels in the latest two measurements. must have measurable active or symptomatic disease. Measurable disease may be paraprotein or free light chains in serum or urine, or the presence of bone marrow plasma cells, defined by one or more of the following criteria: Presence of serum M-protein concentration > 1g/dL. Urine M-protein excretion > 200mg in 24-hour urine collection. Serum free light chain concentration ≥ 10mg/dL and abnormal kappa/lambda ratio. Urine free light chain concentration ≥ 100mg/L and abnormal kappa/lambda ratio. Bone marrow plasma cell percentage ≥ 30% (if no detectable M-protein or FLC.) Age > 18 years of age. If female with reproductive capacity: on effective means of birth control during the entire duration of the treatment. Patients must have recovered from acute toxicities resulting from therapy administered prior to entering this study to grade 1 or less (CTCAE 4) Alopecia may not be resolved. Ability to understand and willingness to sign a written informed consent document. Life expectancy of greater than 8 weeks. ECOG performance status 0, 1, or 2 (Karnofsky > 60%; see Appendix A). have adequate bone marrow function as defined below: absolute neutrophil count > 500/ul platelets > 30,000/ul have adequate liver function as defined below: total bilirubin < 2 times the upper limit of normal AST(SGOT), ALT(SGPT) < 3 x upper limit of normal have adequate renal function as defined by a creatinine clearance > 40 mL/min (measured or estimated by the Cockcroft-Gault formula). have no signs of significant rhabdomyolysis determined by CPK levels with a CK < 5 times the upper limit of normal. Exclusion Criteria: have not received any chemotherapy treatment for multiple myeloma prior to being enrolled in the study. show progressive disease or are not tolerating current chemotherapy regimen. were receiving simvastatin (dose > 40mg/day) while receiving current chemotherapy regimen for multiple myeloma. failed or progressed on more than two chemotherapy regimens, including current treatment; prior to enrolling in this study. receiving any other investigational agent(s). Active second malignancy in the last 5 years except for non-melanoma skin cancer or carcinoma-in-situ. Pregnant women are ineligible, as treatment involves unforeseeable risks to the embryo or fetus. Female patients with reproductive capacity are required to use effective means of birth control during the entire duration of the treatment. History of hypersensitivity reactions attributed to simvastatin or zoledronic acid. receiving medications that may increase risk of rhabdomyolysis such as itraconazole, ketoconazole, erythromycin, cyclosporine, amiodarone, verapamil, clarithromycin, nefazodone, ranolazine, HIV protease inhibitors, gemfibrozil, posaconazole, danazol, amiodarone, diltiazem and amlodipine. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myopathy, untreated hypothyroidism, hereditary myopathy in the family history, unstable angina pectoris, liver disease not due to multiple myeloma, cardiac arrhythmia that is symptomatic or not rate controlled, active connective tissue disease, active autoimmune disease, or psychiatric illness/social situations that would limit compliance with study requirements.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Arm<br>Study Arm | Drug: Simvastatin and zoledronic acid<br>* Simvastatin 80 mg PO daily starting two days before starting chemotherapy and stopping two days after chemotherapy. Zoledronic acid 4 mg IV over 15 minutes on day 1 and then monthly.<br>* Other names: Zocor;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Paraprotein Level and Free Light Chain (FLC) Ratio From Baseline Measurement | The effect of simvastatin and zolendronic acid on M-Protein and FLC ratio will be measured 4 weeks after treatment begins, then every 4 weeks until progression of disease. | 4 weeks after treatment begins |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | OS(Overall survival) is measured from date of study enrollment until death. | At start of year 2 of follow-up on all surviving participants |
| Duration of Response | Response will be accessed by one of the study investigators at each monthly follow up visit during year one. | Year 1 follow up visits occur monthly |
| Progression Free Survival (PFS) | Study will estimate PFS when there is one year of follow up data for all surviving participants | At start of year 2 follow up on all surviving participants |
| Duration of Response | Response will be assessed by one of the study investigators at each three month follow up visit for Year 2 | Year 2 follow up visit occur every three months |
| Duration of Response | Response will be assessed by one of the study investigators at each six month follow up visit for Year 3-5 | Year 3-5 follow up visit occurs every six months |
| Incidence Rate of Toxicity | Descriptive statistics will be provided regarding incidence rates of toxicity. Patients will be monitored for safety throughout the study. | Every 12 months up to one month after treatment completion |
| Comparison of Quality of Life Scores | The QOL scores taken at the start of the study and every 4 months after treatment starts will be analyzed using Wilcoxon test for paired differences | Up to 2 months after last treatment has been completed |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
refractory multiple myeloma
|
NCT03225443
|
Observation and Evaluation of Short-term Curative Effect of Local Advanced Cervical Cancer Treated With Particle Radiotherapy Versus Neoadjuvant Chemotherapy
|
Locally advanced cervical cancer (LACC) refers to the clinically cervical visible lesion with a diameter of > 4 cm, which has been considered as a high risk of early cervical cancer for a long time. Because of local bulk lesion of LACC, the risk of radical hysterectomy is pretty high and the radical effect commonly does not meet the satisfactory. Therefore, 1-3 course of neoadjuvant chemotherapy (NACT) were carried out before operation. However, nearly 20% of patients are not sensitive to NACT. Therefore NACT did not bring any benefits to radical surgery even to some extent delayed the treatment.~Traditional radiotherapy is also commonly used in the treatment of LACC, however ovarian function would be permanently destroyed especially for young patients, additionally radioactive complications to adjacent organs of cervical such as vagina, bladder and rectal also commonly happened, moreover sexual dysfunction after radiotherapy significantly affect the life quality of young patients.~Particle radiotherapy developed recently, has the advantages of short course of treatment and mild side effects, due to its special working mechanism, Bragg effect. So the amount of radiation in the tumor tissue is very extremely high, and in the adjacent tissue is quiet low, therefore the organs at risk were protected by avoiding unnecessary damage.~Based on these, we proposed the application of particle radiotherapy in LACC pre-operation, and comprehensively evaluated recent curative effect, complications and long-term follow-up between particle radiotherapy and NACT. Furthermore, the clinical significance and long-term application prospects about particle therapy were objectively assessed.
|
Shanghai First Maternity and Infant Hospital
|
Uterine Cervical Neoplasms, Locally Advanced Cervical Cancer
|
Inclusion Criteria:~Pathological diagnosis: squamous carcinoma, adenocarcinoma, adenosquamous carcinoma~The pathological staging: IB2，IIA2~Exclusion Criteria:~Underwent surgery or radiation and chemotherapy
| null | null |
Female
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The recurrence rate | | 3 years after treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The transfer rate | | 3 years after treatment |
| mortality | | 3 years after treatment |
|
Locally advanced cervical cancer, Particle radiotherapy, Neoadjuvant Chemotherapy
|
Uterine Cervical Neoplasms, Uterine Neoplasms, Genital Neoplasms, Female, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Uterine Cervical Diseases, Uterine Diseases, Genital Diseases, Female, Female Urogenital Diseases, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Genital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Particle Radiotherapy<br>The patients will receive particle radiotherapy before operation,and then radical hysterectomy, removal of pelvic lymph nodes and abdominal aorta lymph nodes would be conducted. Besides ovary reservation would be made according to the individual situation. Concurrent radiation and chemotherapy would be performed according to the clinical situation. | |
| Neoadjuvant Chemotherapy<br>The patients will receive NACT before operation,and then radical hysterectomy, removal of pelvic lymph nodes and abdominal aorta lymph nodes would be conducted. Besides ovary reservation would be made according to the individual situation. Concurrent radiation and chemotherapy would be performed according to the clinical situation. | |
|
Observation and Evaluation of Short-term Curative Effect of Local Advanced Cervical Cancer Treated With Particle Radiotherapy Versus Neoadjuvant Chemotherapy
Study Overview
=================
Brief Summary
-----------------
Locally advanced cervical cancer (LACC) refers to the clinically cervical visible lesion with a diameter of > 4 cm, which has been considered as a high risk of early cervical cancer for a long time. Because of local bulk lesion of LACC, the risk of radical hysterectomy is pretty high and the radical effect commonly does not meet the satisfactory. Therefore, 1-3 course of neoadjuvant chemotherapy (NACT) were carried out before operation. However, nearly 20% of patients are not sensitive to NACT. Therefore NACT did not bring any benefits to radical surgery even to some extent delayed the treatment. Traditional radiotherapy is also commonly used in the treatment of LACC, however ovarian function would be permanently destroyed especially for young patients, additionally radioactive complications to adjacent organs of cervical such as vagina, bladder and rectal also commonly happened, moreover sexual dysfunction after radiotherapy significantly affect the life quality of young patients. Particle radiotherapy developed recently, has the advantages of short course of treatment and mild side effects, due to its special working mechanism, Bragg effect. So the amount of radiation in the tumor tissue is very extremely high, and in the adjacent tissue is quiet low, therefore the organs at risk were protected by avoiding unnecessary damage. Based on these, we proposed the application of particle radiotherapy in LACC pre-operation, and comprehensively evaluated recent curative effect, complications and long-term follow-up between particle radiotherapy and NACT. Furthermore, the clinical significance and long-term application prospects about particle therapy were objectively assessed.
Official Title
-----------------
Shanghai First Maternity and Infant Hospital
Conditions
-----------------
Uterine Cervical Neoplasms, Locally Advanced Cervical Cancer
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathological diagnosis: squamous carcinoma, adenocarcinoma, adenosquamous carcinoma The pathological staging: IB2，IIA2 Exclusion Criteria: Underwent surgery or radiation and chemotherapy
Sexes Eligible for Study
-----------------
Female
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Particle Radiotherapy<br>The patients will receive particle radiotherapy before operation,and then radical hysterectomy, removal of pelvic lymph nodes and abdominal aorta lymph nodes would be conducted. Besides ovary reservation would be made according to the individual situation. Concurrent radiation and chemotherapy would be performed according to the clinical situation. | |
| Neoadjuvant Chemotherapy<br>The patients will receive NACT before operation,and then radical hysterectomy, removal of pelvic lymph nodes and abdominal aorta lymph nodes would be conducted. Besides ovary reservation would be made according to the individual situation. Concurrent radiation and chemotherapy would be performed according to the clinical situation. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The recurrence rate | | 3 years after treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The transfer rate | | 3 years after treatment |
| mortality | | 3 years after treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Locally advanced cervical cancer, Particle radiotherapy, Neoadjuvant Chemotherapy
|
|||
NCT03101293
|
A Study to Evaluate the Effect of Food on the Pharmacokinetics of TAK-831 Tablet Formulation
|
The purpose of this study is to determine the pharmacokinetic (PK) of a single oral dose of TAK-831 400 milligram (mg) in the fasted state and to estimate the effect of food on the PK of a single oral dose of TAK-831 400 mg when administered as tablet formulation in healthy participants.
|
The drug being tested in this study is called TAK-831. TAK-831 is being tested in healthy participants under fasting and fed conditions in order to determine the effect of food on the PK of single oral dose of TAK-831 tablet formulation. The study will enroll approximately 16 participants. Participants will be randomly and equally assigned (by chance, like flipping a coin) to 1 of the 2 treatment sequences following as:~TAK-831 400 mg Fasted + TAK-831 400 mg Fed~TAK-831 400 mg Fed + TAK-831 400 mg Fasted All participants will be asked to take single oral dose of TAK-831 tablet at the same time on Day 1 of each Intervention Period. This single center trial will be conducted in the United States. The overall time to participate in this study is 23 days. Participants will visit the clinic on Day -1 and remained confined until Day 3 of Intervention Period 1 and 2. A washout period of minimum 7 days will be maintained between the doses in each Intervention Period. Participants will make 3 visits to the clinic on Days 4, 6 and 8 on each Intervention Period and will be contacted by telephone 14 days after the last dose of study drug (Day 23) for a follow-up assessment.
|
A Randomized, Open-Label, Single-Dose, 2-Period, Crossover Design, Phase 1 Study to Evaluate the Effect of Food on the Pharmacokinetics of TAK-831 T2 Tablet Formulation in Healthy Subjects
|
Healthy Volunteers
|
* Drug: TAK-831
|
Inclusion Criteria:~1. Weighs greater than or equal to (>=) 45 kilogram (kg) and has a body mass index (BMI) between 18.0 and 30.0 kilogram per square meter (kg/m^2), inclusive at Screening.~Exclusion Criteria:~Has received TAK-831 in a previous clinical study.~Has poor peripheral venous access.~Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days prior to first dose of study drug.~Has any dietary restrictions or preferences that may interfere with the conduct of the study.
|
18 Years
|
55 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax: Maximum Observed Plasma Concentration for TAK-831 | | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) | | Day 1 |
|
Drug therapy
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-831 400 mg Fasted + TAK-831 400 mg Fed<br>TAK-831 400 mg, film-coated tablets, orally under fasted state, once on Day 1 of Intervention Period 1, followed by 7 days washout period, further followed by TAK-831 400 mg, film-coated tablets, orally under fed state, once on Day 1 of Intervention Period 2. | Drug: TAK-831<br>* TAK-831 film-coated tablet.<br>|
| Experimental: TAK-831 400 mg Fed + TAK-831 400 mg Fasted<br>TAK-831 400 mg, film-coated tablets, orally under fed state, once on Day 1 of Intervention Period 1, followed by 7 days washout period, further followed by TAK-831 400 mg, film-coated tablets, orally under fasted state, once on Day 1 of Intervention Period 2. | Drug: TAK-831<br>* TAK-831 film-coated tablet.<br>|
|
A Study to Evaluate the Effect of Food on the Pharmacokinetics of TAK-831 Tablet Formulation
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the pharmacokinetic (PK) of a single oral dose of TAK-831 400 milligram (mg) in the fasted state and to estimate the effect of food on the PK of a single oral dose of TAK-831 400 mg when administered as tablet formulation in healthy participants.
Detailed Description
-----------------
The drug being tested in this study is called TAK-831. TAK-831 is being tested in healthy participants under fasting and fed conditions in order to determine the effect of food on the PK of single oral dose of TAK-831 tablet formulation. The study will enroll approximately 16 participants. Participants will be randomly and equally assigned (by chance, like flipping a coin) to 1 of the 2 treatment sequences following as: TAK-831 400 mg Fasted + TAK-831 400 mg Fed TAK-831 400 mg Fed + TAK-831 400 mg Fasted All participants will be asked to take single oral dose of TAK-831 tablet at the same time on Day 1 of each Intervention Period. This single center trial will be conducted in the United States. The overall time to participate in this study is 23 days. Participants will visit the clinic on Day -1 and remained confined until Day 3 of Intervention Period 1 and 2. A washout period of minimum 7 days will be maintained between the doses in each Intervention Period. Participants will make 3 visits to the clinic on Days 4, 6 and 8 on each Intervention Period and will be contacted by telephone 14 days after the last dose of study drug (Day 23) for a follow-up assessment.
Official Title
-----------------
A Randomized, Open-Label, Single-Dose, 2-Period, Crossover Design, Phase 1 Study to Evaluate the Effect of Food on the Pharmacokinetics of TAK-831 T2 Tablet Formulation in Healthy Subjects
Conditions
-----------------
Healthy Volunteers
Intervention / Treatment
-----------------
* Drug: TAK-831
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Weighs greater than or equal to (>=) 45 kilogram (kg) and has a body mass index (BMI) between 18.0 and 30.0 kilogram per square meter (kg/m^2), inclusive at Screening. Exclusion Criteria: Has received TAK-831 in a previous clinical study. Has poor peripheral venous access. Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days prior to first dose of study drug. Has any dietary restrictions or preferences that may interfere with the conduct of the study.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-831 400 mg Fasted + TAK-831 400 mg Fed<br>TAK-831 400 mg, film-coated tablets, orally under fasted state, once on Day 1 of Intervention Period 1, followed by 7 days washout period, further followed by TAK-831 400 mg, film-coated tablets, orally under fed state, once on Day 1 of Intervention Period 2. | Drug: TAK-831<br>* TAK-831 film-coated tablet.<br>|
| Experimental: TAK-831 400 mg Fed + TAK-831 400 mg Fasted<br>TAK-831 400 mg, film-coated tablets, orally under fed state, once on Day 1 of Intervention Period 1, followed by 7 days washout period, further followed by TAK-831 400 mg, film-coated tablets, orally under fasted state, once on Day 1 of Intervention Period 2. | Drug: TAK-831<br>* TAK-831 film-coated tablet.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax: Maximum Observed Plasma Concentration for TAK-831 | | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 | | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
| AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 | | Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) | | Day 1 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug therapy
|
|
NCT04067518
|
A Clinical Study of SHP674 (Pegaspargase) in Participants With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia
|
The objectives of the study are to assess the safety and tolerability of a single dose of SHP674 in Japanese participants (dose confirmation) in the tolerability assessment period of Part 1 and to assess the safety, pharmacokinetics and efficacy of SHP674 dose in Part 2 (found to be tolerated in Part 1) in the treatment of newly diagnosed untreated acute lymphoblastic leukemia (ALL) in Japanese participants.
|
A Phase 2 Clinical Study of SHP674 in Patients With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia
|
Acute Lymphoblastic Leukemia
|
* Biological: SHP674
|
Inclusion Criteria:~Age 1 to ≤21 years at the time of informed consent;~Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2;~Newly diagnosed, untreated precursor B-cell ALL~No prior therapy for malignant tumor such as chemotherapy and radiation therapy before signing the informed consent;~Life expectancy of at least 6 months from the date of enrollment;~Exclusion Criteria:~Mature B-cell ALL ; Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL~Preexisting known coagulopathy ;~History of pancreatitis;~Continuous use of corticosteroids;~Prior treatment or possible prior treatment with an L-asparaginase preparation;~History of sensitivity to polyethylene glycol (PEG) or PEG-based drugs;~Pregnant
|
1 Year
|
21 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The intervention study model is sequential in results section of record.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period | An adverse event (AE) is defined as any untoward medical occurrence in a participant after signing informed consent. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease, whether or not it is related to the investigational product. TEAE is defined as any untoward medical occurrence in a participant who received an investigational product which occurs during the period from Day 1 of the pre-treatment phase to 30 (+7) days after the last dose of investigational product, or until the start of a new therapy, whichever occurs first. A related adverse event signifies that there is a reasonable causal relationship between study treatment and an AE. | Up to 30 days after last dose of study drug (approximately 49 weeks) |
| Part 2: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674 | | 14 days after the first dose of SHP674 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2) | | Predose and 25 days post dose (Part 1 and Part 2) |
| Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2) | | Predose and 25 days post dose (Part 1 and part 2) |
| Part 1: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 IU/mL 14 Days (336 Hours) After the First Dose of SHP674 | | 14 days after the first dose of SHP674 |
| Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | | Day 1 (pre-dose, 5 min, 4 hours, 24 hours post dose), Days 2, 4, 11, 14, 18, 25 post dose |
| Survival Rate at 1 Year After the Start of Study Treatment | Survival rate is defined as the percentage of subjects who survived at 1 year after the start of study treatment. | 1 year after the start of study treatment (from first dose up to 12 months) |
| Event-free Survival Rate at 1 Year After the Start of Study Treatment | Event-free survival rate is defined as percentage of subjects who did not experience any event and survived at 1 year after the start of study treatment. | 1 year after the start of study treatment (from first dose up to 12 months) |
|
Acute Lymphoblastic Leukemia
|
Pegaspargase, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHP674<br>Part 1: Participants with ALL who were stratified into the standard risk (SR) or intermediate risk (IR) groups received total 3 doses of SHP674 in the 36-week treatment period and who were stratified into the high risk (HR) group received total 8 doses of SHP674 in the 45-week treatment period.~Part 2: Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674 in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674 in the 45-week treatment period. | Biological: SHP674<br>* SHP674: powder for solution for injection, IV (administered by 1 to 2 hours of drip infusion), dose determination : if BSA ≥0.6 m^2: 2500 IU/m^2 every 14 days if BSA <0.6 m^2: 82.5 IU/kg every 14 days<br>* Other names: Pegaspargase;|
|
A Clinical Study of SHP674 (Pegaspargase) in Participants With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia
Study Overview
=================
Brief Summary
-----------------
The objectives of the study are to assess the safety and tolerability of a single dose of SHP674 in Japanese participants (dose confirmation) in the tolerability assessment period of Part 1 and to assess the safety, pharmacokinetics and efficacy of SHP674 dose in Part 2 (found to be tolerated in Part 1) in the treatment of newly diagnosed untreated acute lymphoblastic leukemia (ALL) in Japanese participants.
Official Title
-----------------
A Phase 2 Clinical Study of SHP674 in Patients With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia
Conditions
-----------------
Acute Lymphoblastic Leukemia
Intervention / Treatment
-----------------
* Biological: SHP674
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 1 to ≤21 years at the time of informed consent; Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2; Newly diagnosed, untreated precursor B-cell ALL No prior therapy for malignant tumor such as chemotherapy and radiation therapy before signing the informed consent; Life expectancy of at least 6 months from the date of enrollment; Exclusion Criteria: Mature B-cell ALL ; Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL Preexisting known coagulopathy ; History of pancreatitis; Continuous use of corticosteroids; Prior treatment or possible prior treatment with an L-asparaginase preparation; History of sensitivity to polyethylene glycol (PEG) or PEG-based drugs; Pregnant
Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 21 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The intervention study model is sequential in results section of record.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHP674<br>Part 1: Participants with ALL who were stratified into the standard risk (SR) or intermediate risk (IR) groups received total 3 doses of SHP674 in the 36-week treatment period and who were stratified into the high risk (HR) group received total 8 doses of SHP674 in the 45-week treatment period. Part 2: Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674 in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674 in the 45-week treatment period. | Biological: SHP674<br>* SHP674: powder for solution for injection, IV (administered by 1 to 2 hours of drip infusion), dose determination : if BSA ≥0.6 m^2: 2500 IU/m^2 every 14 days if BSA <0.6 m^2: 82.5 IU/kg every 14 days<br>* Other names: Pegaspargase;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period | An adverse event (AE) is defined as any untoward medical occurrence in a participant after signing informed consent. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease, whether or not it is related to the investigational product. TEAE is defined as any untoward medical occurrence in a participant who received an investigational product which occurs during the period from Day 1 of the pre-treatment phase to 30 (+7) days after the last dose of investigational product, or until the start of a new therapy, whichever occurs first. A related adverse event signifies that there is a reasonable causal relationship between study treatment and an AE. | Up to 30 days after last dose of study drug (approximately 49 weeks) |
| Part 2: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674 | | 14 days after the first dose of SHP674 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) (Part 1 and Part 2) | | Predose and 25 days post dose (Part 1 and Part 2) |
| Percentage of Participants With Anti-Polyethylene Glycol (PEG) Antibody (Part 1 and Part 2) | | Predose and 25 days post dose (Part 1 and part 2) |
| Part 1: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 IU/mL 14 Days (336 Hours) After the First Dose of SHP674 | | 14 days after the first dose of SHP674 |
| Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL | | Day 1 (pre-dose, 5 min, 4 hours, 24 hours post dose), Days 2, 4, 11, 14, 18, 25 post dose |
| Survival Rate at 1 Year After the Start of Study Treatment | Survival rate is defined as the percentage of subjects who survived at 1 year after the start of study treatment. | 1 year after the start of study treatment (from first dose up to 12 months) |
| Event-free Survival Rate at 1 Year After the Start of Study Treatment | Event-free survival rate is defined as percentage of subjects who did not experience any event and survived at 1 year after the start of study treatment. | 1 year after the start of study treatment (from first dose up to 12 months) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute Lymphoblastic Leukemia
|
|
NCT01112501
|
SPECT/CT in the Diagnosis of Dementia
|
Aim of the study is to evaluate whether Tc-99m-ECD-SPECT/CT enhances early diagnosis of dementia in two specific patient groups: (1) patient with mild cognitive impairment, and (2) patient with possible symptoms and signs of frontotemporal dementia. Evaluation of SPECT/CT data is performed both by visual and quantitative voxel-based analyses (Statistical Parametric Mapping). The final diagnosis is based on up to four years clinical follow-up.
|
SPECT/CT in the Diagnosis of Dementia
|
Dementia
|
Inclusion Criteria (one of these):~healthy control~mild cognitive impairment (recruited from a population based data)~clinically suspected frontotemporal dementia (unset diagnosis)~Exclusion Criteria:~unable to be scanned with SPECT/CT
| null | null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final diagnosis | (1) controls, (2) stable mild cognitive impairment (MCI), (3)MCI converted to Alzheimers's disease (AD), (4) frontotemporal dementia (FTD), suspected FTD converted to AD, (5) other final diagnoses | 4 years |
|
Diagnosis, Dementia, Imaging
|
Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Neurocognitive Disorders, Mental Disorders
|
SPECT/CT in the Diagnosis of Dementia
Study Overview
=================
Brief Summary
-----------------
Aim of the study is to evaluate whether Tc-99m-ECD-SPECT/CT enhances early diagnosis of dementia in two specific patient groups: (1) patient with mild cognitive impairment, and (2) patient with possible symptoms and signs of frontotemporal dementia. Evaluation of SPECT/CT data is performed both by visual and quantitative voxel-based analyses (Statistical Parametric Mapping). The final diagnosis is based on up to four years clinical follow-up.
Official Title
-----------------
SPECT/CT in the Diagnosis of Dementia
Conditions
-----------------
Dementia
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (one of these): healthy control mild cognitive impairment (recruited from a population based data) clinically suspected frontotemporal dementia (unset diagnosis) Exclusion Criteria: unable to be scanned with SPECT/CT
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final diagnosis | (1) controls, (2) stable mild cognitive impairment (MCI), (3)MCI converted to Alzheimers's disease (AD), (4) frontotemporal dementia (FTD), suspected FTD converted to AD, (5) other final diagnoses | 4 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diagnosis, Dementia, Imaging
|
|||||
NCT03589872
|
The Fine Motor Dexterity Under Dual Task in Parkinson's Disease
|
This study was planned to investigate the contribution of dual task interference on dexterity related ADL disability in patients with Parkinson's disease. We hypothesised that the dual task interference is an indicator of dexterity related ADL difficulties.
|
We planned this study as a cross sectional trial. 53 patients with Parkinson's disease will be evaluated under 2 different task by nine hole peg test. Besides this assessment the cardinal symptoms (bradykinesia, tremor, rigidity) will be evaluated to determine their contribution on the ADL performance.
|
The Contribution of the Dual Task Interference on the Dexterity Related Activities of Daily Living in Parkinson's Disease
|
Fine Motor Skill Dysfunction, Parkinson Disease
|
* Diagnostic Test: Fine motor dexterity test, nine hole peg test
|
Inclusion Criteria:~Diagnosis of idiopathic Parkinson's disease according to the criteria of the United Kingdom brain Bank by neurologist~Age 50-90 range~having sufficient cognitive status according to the Mini Mental Status Evaluation (24 or above from the Mini Mental Test)~Exclusion Criteria:~Having orthopedic and neurological disorders affecting hand function,~Having sensory problems,~Having Diabetus mellitus
|
50 Years
|
90 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nine hole peg test | The Nine-Hole Peg Test is used to measure finger dexterity in patients with various neurological diagnoses. The patient must pick up the pegs from the holes and replace them back as fast as possible. The Nine Hole Peg Test should be conducted with the dominant arm first, then nondominant hand. The time will be recorded in second to complete the test. The test will be performed under three task;~single task: Only nine-hole peg test~adding a cognitive task: Nine-hole peg test will be performed with a concurrent cognitive task. The cognitive task is a serial 7 subtraction from numbers changed between 290 and 310 during the performing nine-hole peg test. The time will be recorded. | 5 minutes |
| ADL-related dexterity Questionnaire 24 (DextQ-24) | Dexterity-related ADL difficulties were measured by the ADL-related dexterity Questionnaire 24 (DextQ-24), including 24 question dealing with bimanual and unimanual activities, which is a reliable and valid disease specific questionnaire to evaluate dexterity in patients with PD. Each question is scored between 1 (no problems) and 4 (need aid to perform task) by the patient's experience. Total score ranged from 24 points to 96 points. | 10 minutes |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Hoehn and Yahr Scale | Disease progression will be assessed with modified Hoehn and Yahr Scale. The original scale included stages 1 through 5. Since then, stage 0 has been added, and stages 1.5 and 2.5 have been proposed. This modified scale allocates stages from 0 to 5 to indicate the relative level of disability.~Stage 0: No signs of disease.~Stage 1: Unilateral symptoms only.~Stage 1.5: Unilateral and axial involvement.~Stage 2: Bilateral symptoms. No impairment of balance.~Stage 2.5: Mild bilateral disease with recovery on pull test.~Stage 3: Balance impairment. Mild to moderate disease. Physically independent.~Stage 4: Severe disability, but still able to walk or stand unassisted.~Stage 5: Needing a wheelchair or bedridden unless assisted. | 2 minutes |
| Unified Parkinson's Disease Rating Scale (UPDRS) - Section of Activities of Daily Living (ADL) | The UPDRS- ADL section evaluates the impact of Parkinson disease on ADL according to patient's perspective. The ADL section consists of 13 items for gathering information on the patient's own perception of functional impairment due to PD. Each item scores between 0-4. 0 means normal and 4 means severe impairment. The total score change between 0-52. High scores indicate severe impairment. | 10 minutes |
| Unified Parkinson's Disease Rating Scale (UPDRS) - Motor Section | Motor section of UPDRS determines the impairment due to the Parkinson's disease. Rigidity, bradykinesia and tremor items which are relating with upper extremity function will be assessed. Each item scores between 0-4. 0 means normal and 4 means severe impairment. The total scores of rigidity, bradykinesia, and tremor, respectively range between 0-8, 0-24 and 0-16. | 10 minutes |
|
hand function, dual task, Parkinson disease, activities of daily living
|
Parkinson Disease, Parkinsonian Disorders, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Synucleinopathies, Neurodegenerative Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Group<br>patients with parkinson disease | Diagnostic Test: Fine motor dexterity test, nine hole peg test<br>* The nine hole peg test will be performed under two different task (1)single task, (2)adding a cognitive task<br>|
|
The Fine Motor Dexterity Under Dual Task in Parkinson's Disease
Study Overview
=================
Brief Summary
-----------------
This study was planned to investigate the contribution of dual task interference on dexterity related ADL disability in patients with Parkinson's disease. We hypothesised that the dual task interference is an indicator of dexterity related ADL difficulties.
Detailed Description
-----------------
We planned this study as a cross sectional trial. 53 patients with Parkinson's disease will be evaluated under 2 different task by nine hole peg test. Besides this assessment the cardinal symptoms (bradykinesia, tremor, rigidity) will be evaluated to determine their contribution on the ADL performance.
Official Title
-----------------
The Contribution of the Dual Task Interference on the Dexterity Related Activities of Daily Living in Parkinson's Disease
Conditions
-----------------
Fine Motor Skill Dysfunction, Parkinson Disease
Intervention / Treatment
-----------------
* Diagnostic Test: Fine motor dexterity test, nine hole peg test
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of idiopathic Parkinson's disease according to the criteria of the United Kingdom brain Bank by neurologist Age 50-90 range having sufficient cognitive status according to the Mini Mental Status Evaluation (24 or above from the Mini Mental Test) Exclusion Criteria: Having orthopedic and neurological disorders affecting hand function, Having sensory problems, Having Diabetus mellitus
Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 90 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Group<br>patients with parkinson disease | Diagnostic Test: Fine motor dexterity test, nine hole peg test<br>* The nine hole peg test will be performed under two different task (1)single task, (2)adding a cognitive task<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nine hole peg test | The Nine-Hole Peg Test is used to measure finger dexterity in patients with various neurological diagnoses. The patient must pick up the pegs from the holes and replace them back as fast as possible. The Nine Hole Peg Test should be conducted with the dominant arm first, then nondominant hand. The time will be recorded in second to complete the test. The test will be performed under three task; single task: Only nine-hole peg test adding a cognitive task: Nine-hole peg test will be performed with a concurrent cognitive task. The cognitive task is a serial 7 subtraction from numbers changed between 290 and 310 during the performing nine-hole peg test. The time will be recorded. | 5 minutes |
| ADL-related dexterity Questionnaire 24 (DextQ-24) | Dexterity-related ADL difficulties were measured by the ADL-related dexterity Questionnaire 24 (DextQ-24), including 24 question dealing with bimanual and unimanual activities, which is a reliable and valid disease specific questionnaire to evaluate dexterity in patients with PD. Each question is scored between 1 (no problems) and 4 (need aid to perform task) by the patient's experience. Total score ranged from 24 points to 96 points. | 10 minutes |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Hoehn and Yahr Scale | Disease progression will be assessed with modified Hoehn and Yahr Scale. The original scale included stages 1 through 5. Since then, stage 0 has been added, and stages 1.5 and 2.5 have been proposed. This modified scale allocates stages from 0 to 5 to indicate the relative level of disability. Stage 0: No signs of disease. Stage 1: Unilateral symptoms only. Stage 1.5: Unilateral and axial involvement. Stage 2: Bilateral symptoms. No impairment of balance. Stage 2.5: Mild bilateral disease with recovery on pull test. Stage 3: Balance impairment. Mild to moderate disease. Physically independent. Stage 4: Severe disability, but still able to walk or stand unassisted. Stage 5: Needing a wheelchair or bedridden unless assisted. | 2 minutes |
| Unified Parkinson's Disease Rating Scale (UPDRS) - Section of Activities of Daily Living (ADL) | The UPDRS- ADL section evaluates the impact of Parkinson disease on ADL according to patient's perspective. The ADL section consists of 13 items for gathering information on the patient's own perception of functional impairment due to PD. Each item scores between 0-4. 0 means normal and 4 means severe impairment. The total score change between 0-52. High scores indicate severe impairment. | 10 minutes |
| Unified Parkinson's Disease Rating Scale (UPDRS) - Motor Section | Motor section of UPDRS determines the impairment due to the Parkinson's disease. Rigidity, bradykinesia and tremor items which are relating with upper extremity function will be assessed. Each item scores between 0-4. 0 means normal and 4 means severe impairment. The total scores of rigidity, bradykinesia, and tremor, respectively range between 0-8, 0-24 and 0-16. | 10 minutes |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hand function, dual task, Parkinson disease, activities of daily living
|
|
NCT05156723
|
Study of the Immunogenicity, Safety and Tolerability of the Convacell Vaccine.
|
A two-stage trial will involve healthy volunteers. The first stage is open trial, and the second stage is a double-blind trial with randomization of volunteers into three groups. At stage I of the trial, the maximum number of screened healthy volunteers will be 30 of which 20 men aged 18 to over 60 years. At stage II of the trial, the maximum number of screened healthy volunteers will be 150, of which 135 men and women aged 18 to over 60 years eligible according to the inclusion and exclusion criteria are planned to be included and randomized to collect data that will be used for the subsequent safety and immunogenicity assessment. The enrollment of volunteers at stage II will be competitive.
|
Trial product is subunit recombinant vaccine for the prevention of coronavirus infection caused by the SARS-CoV-2 virus.~Vaccination forms humoral and cellular immunity that prevents the development of coronavirus infection caused by the SARS-CoV-2 virus. On the surface of excipients emulsion droplets N-protein is presented to monocytes attracted from the bloodstream due to a local increase in the level of cytokines. Antigen-bearing cells migrate to draining lymph nodes with activation of innate and adaptive immunity cells in them. Due to the activation of natural killer cells in combination with specific antibodies, the mechanism of lysis of infected cells is realized. The nucleocapsid protein (N) is conserved and little susceptible to mutational changes. This makes the vaccine based on it universal for various strains of coronavirus
|
A Double-blind, Randomized, Prospective, Placebo-controlled Trial to Assess the Immunogenicity, Safety, and Tolerability of a Coronavirus Vaccine in Healthy Volunteers Aged 18 to 60 Years
|
COVID-19, Immunologic Factors, Coronavirus Infections, Respiratory Tract Infections
|
* Biological: Subunit recombinant vaccine for the prevention of coronavirus infection
* Biological: Placebo
|
Inclusion Criteria:~Healthy men and women aged 18 to 60 years old, inclusive.~Written informed consent of the volunteer to participate in the clinical trial;~BMI within the range of 18.5 ≤ BWI ≤ 30 kg/m2 with the body weight of not less than 55 kg for men, not less than 45 kg for women and not more than 100 kg for volunteers of both sexes.~Verified healthy status: no deviations from reference values of standard clinical, laboratory and instrumental examinations.~Negative HIV 1&2, RPR, HВsAg and HCV RNA tests.~Hemodynamic and other vital signs are within normal limits (reference intervals are 60-90 beats/min at rest for HR, up to 22 per minute for RR, body temperature from 35.5 to 36.9 °C; systolic blood pressure (SBP) is considered normal in the range of 100-139 mmHg, diastolic blood pressure (DBP) - in the range of 60-89 mmHg);~Volunteers able to fulfill requirements of the Protocol (i.e., fill out the patient's diary, come to follow-up visits);~Abstinence from alcohol for 14 days before the start of the trial and until the end of participation in the trial;~Abstinence from smoking for 48 hours before the start of the trial and during hospitalization;~For fertile women - a negative result of the pregnancy test and consent to observe adequate methods of contraception during the trial and at least two months after vaccination;~For fertile men - consent to observe adequate methods of contraception during the trial and at least two months after vaccination, except for men after vasectomy with documented azoospermia, and their sexual partners should use methods of contraception that ensure more than 90% reliability or be incapable of conception after a surgical sterilization or have a natural menopause for at least 2 years~Exclusion Criteria:~History of influenza or acute respiratory viral infection (ARVI) within 2 months before the start of the trial.~A serious post-vaccination reaction (temperature above 40 °C, hyperemia or edema more than 8 cm in diameter) or complications (collapse or shock-like condition that developed within 48 hours after vaccination; convulsions accompanied or not accompanied by a fever due to any previous vaccination).~Fever, cough, and shortness of breath within 30 days before vaccination.~History of COVID-19.~Positive result of the COVID-19 PCR test.~Body temperature ≥ 37,0°C.~History of allergies.~Any vaccination within 30 days before the screening.~History of leukemia, tuberculosis, cancer, autoimmune diseases.~History of Quincke's edema.~Positive blood test results for HIV, syphilis, hepatitis B/C.~Volunteers who received immunoglobulin during the last three months before the trial.~History of long-term use (more than 14 days) of immunosuppressants or other immunomodulatory drugs for six months before the trial.~Treatment with glucocorticosteroids, including in small doses, as well as local use of drugs containing steroids (> 10 mg of prednisolone or its equivalent for more than 14 days before the screening).~History of any confirmed or suspected immunosuppressive or immunodeficiency condition.~History of splenectomy.~History of chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, the gastrointestinal tract, liver, kidneys, hematopoietic or immune systems, mental disease in the acute stage or in the decompensation stage.~Transfusion of blood or blood components within 4 months before screening.~History of acute and chronic infectious diseases.~Consumption of more than 10 units of alcohol per week or history of alcohol addiction, drug addiction or abuse of pharmaceutical products.~Smoking of more than 10 cigarettes per day.~Participation in another clinical trial within the last 90 days.~Pregnancy or lactation.~Coagulopathy, hemophilia, bleeding disorder.~Participation in stage I of this trial (for volunteers of stage II).~Transfusion of COVID-19 convalescent plasma within 14 days before the screening, COVID-19 vaccination less than 30 days before the screening
|
18 Years
|
60 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of actively detected local and systemic AEs (Stage I) | | During 21 days after initial vaccination |
| Incidence of actively detected local and systemic AEs (Stage II) | | During 21 days after initial vaccination |
| Increase in geometric mean titers of antibodies to N-protein of SARS-CoV-2 (Stage II) | Changes from day 0 to days 21 and 42 after the initial vaccination | Days 21 and 42 after the initial vaccination |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of actively detected local AEs | | During 7 days after initial vaccination/revaccination |
| Incidence of actively detected systemic AEs | | During 7 days after initial vaccination/revaccination |
| Incidence of actively detected local AEs | | During 21 days after initial vaccination/revaccination |
| Incidence of actively detected systemic AEs | | During 21 days after initial vaccination/revaccination |
| Incidence of any AEs | | During the trial |
| Number of volunteers hospitalized with COVID-19 | Total number of SARS-CoV-2 infection cases~Total number of COVID-19 cases~Total number of COVID-19 related deaths | During the trial |
| Proportion SARS-CoV-2 seropositive volunteers | | Day 21 (Stage I and Stage II) and Day 42 (Stage II) |
| Change in IFN-γ, IL-2 and IL-4 levels | | Days 14, 21 (Stage I and Stage II) and Days 28, 42, 90 and 180 (Stage II) after vaccination |
| Change in the subpopulation composition of T-lymphocytes | | Days 14, 21 (Stage I and Stage II) and Days 28, 42, 90 and 180 (Stage II) after vaccination |
| Change in titer of antibodies to N-protein of SARS-CoV-2 | | Days 14, 21 (Stage I and Stage II), Days 28, 42, 90 and 180 (Stage II), Days 240, 350 (Stage II, cohort 2) after initial vaccination |
| Change in the antigen-specific cellular immune response (T-cell response) | | Days 14, 21 (Stage II), Days 28, 42, 90 and 180, Days 240, 350 (Stage II, cohort 2) after initial vaccination |
| Incidence of seroconversion (specific antibodies to N-protein of SARS-CoV-2) | | Days 14, 21 (Stage I and Stage II), Days 28, 42, 90 and 180, Days 240, 350 (Stage II, cohort 2) after initial vaccination |
|
COVID-19, COVID, recombinant vaccine, nucleocapsid protein, cellular immunity, SPbSRIVS, Convacell
|
Infections, Communicable Diseases, COVID-19, Coronavirus Infections, Respiratory Tract Infections, Disease Attributes, Pathologic Processes, Pneumonia, Viral, Pneumonia, Virus Diseases, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Subunit recombinant vaccine for the prevention of coronavirus infection<br>5 volunteers have been vaccinated with a single dose (Stage I) | Biological: Subunit recombinant vaccine for the prevention of coronavirus infection<br>* solution for intramuscular injection, 0.5 ml<br>|
| Experimental: Group 2: Subunit recombinant vaccine for the prevention of coronavirus infection<br>15 volunteers have been vaccinated with a single dose (Stage I) | Biological: Subunit recombinant vaccine for the prevention of coronavirus infection<br>* solution for intramuscular injection, 0.5 ml<br>|
| Experimental: Group 3: Subunit recombinant vaccine for the prevention of coronavirus infection<br>45 volunteers will be vaccinated with the coronavirus vaccine intramuscularly twice (Stage II) | Biological: Subunit recombinant vaccine for the prevention of coronavirus infection<br>* solution for intramuscular injection, 0.5 ml<br>|
| Experimental: Group 4: Subunit recombinant vaccine for the prevention of coronavirus infection<br>45 volunteers have been vaccinated with a single dose of the coronavirus vaccine intramuscularly and then treated with a single dose of placebo (Stage II) | Biological: Subunit recombinant vaccine for the prevention of coronavirus infection<br>* solution for intramuscular injection, 0.5 ml<br>|
| Placebo Comparator: Group 5: Placebo<br>45 volunteers have been vaccinated with placebo intramuscularly twice (Stage II) | Biological: Placebo<br>* solution for intramuscular injection, 0.5 ml<br>|
|
Study of the Immunogenicity, Safety and Tolerability of the Convacell Vaccine.
Study Overview
=================
Brief Summary
-----------------
A two-stage trial will involve healthy volunteers. The first stage is open trial, and the second stage is a double-blind trial with randomization of volunteers into three groups. At stage I of the trial, the maximum number of screened healthy volunteers will be 30 of which 20 men aged 18 to over 60 years. At stage II of the trial, the maximum number of screened healthy volunteers will be 150, of which 135 men and women aged 18 to over 60 years eligible according to the inclusion and exclusion criteria are planned to be included and randomized to collect data that will be used for the subsequent safety and immunogenicity assessment. The enrollment of volunteers at stage II will be competitive.
Detailed Description
-----------------
Trial product is subunit recombinant vaccine for the prevention of coronavirus infection caused by the SARS-CoV-2 virus. Vaccination forms humoral and cellular immunity that prevents the development of coronavirus infection caused by the SARS-CoV-2 virus. On the surface of excipients emulsion droplets N-protein is presented to monocytes attracted from the bloodstream due to a local increase in the level of cytokines. Antigen-bearing cells migrate to draining lymph nodes with activation of innate and adaptive immunity cells in them. Due to the activation of natural killer cells in combination with specific antibodies, the mechanism of lysis of infected cells is realized. The nucleocapsid protein (N) is conserved and little susceptible to mutational changes. This makes the vaccine based on it universal for various strains of coronavirus
Official Title
-----------------
A Double-blind, Randomized, Prospective, Placebo-controlled Trial to Assess the Immunogenicity, Safety, and Tolerability of a Coronavirus Vaccine in Healthy Volunteers Aged 18 to 60 Years
Conditions
-----------------
COVID-19, Immunologic Factors, Coronavirus Infections, Respiratory Tract Infections
Intervention / Treatment
-----------------
* Biological: Subunit recombinant vaccine for the prevention of coronavirus infection
* Biological: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy men and women aged 18 to 60 years old, inclusive. Written informed consent of the volunteer to participate in the clinical trial; BMI within the range of 18.5 ≤ BWI ≤ 30 kg/m2 with the body weight of not less than 55 kg for men, not less than 45 kg for women and not more than 100 kg for volunteers of both sexes. Verified healthy status: no deviations from reference values of standard clinical, laboratory and instrumental examinations. Negative HIV 1&2, RPR, HВsAg and HCV RNA tests. Hemodynamic and other vital signs are within normal limits (reference intervals are 60-90 beats/min at rest for HR, up to 22 per minute for RR, body temperature from 35.5 to 36.9 °C; systolic blood pressure (SBP) is considered normal in the range of 100-139 mmHg, diastolic blood pressure (DBP) - in the range of 60-89 mmHg); Volunteers able to fulfill requirements of the Protocol (i.e., fill out the patient's diary, come to follow-up visits); Abstinence from alcohol for 14 days before the start of the trial and until the end of participation in the trial; Abstinence from smoking for 48 hours before the start of the trial and during hospitalization; For fertile women - a negative result of the pregnancy test and consent to observe adequate methods of contraception during the trial and at least two months after vaccination; For fertile men - consent to observe adequate methods of contraception during the trial and at least two months after vaccination, except for men after vasectomy with documented azoospermia, and their sexual partners should use methods of contraception that ensure more than 90% reliability or be incapable of conception after a surgical sterilization or have a natural menopause for at least 2 years Exclusion Criteria: History of influenza or acute respiratory viral infection (ARVI) within 2 months before the start of the trial. A serious post-vaccination reaction (temperature above 40 °C, hyperemia or edema more than 8 cm in diameter) or complications (collapse or shock-like condition that developed within 48 hours after vaccination; convulsions accompanied or not accompanied by a fever due to any previous vaccination). Fever, cough, and shortness of breath within 30 days before vaccination. History of COVID-19. Positive result of the COVID-19 PCR test. Body temperature ≥ 37,0°C. History of allergies. Any vaccination within 30 days before the screening. History of leukemia, tuberculosis, cancer, autoimmune diseases. History of Quincke's edema. Positive blood test results for HIV, syphilis, hepatitis B/C. Volunteers who received immunoglobulin during the last three months before the trial. History of long-term use (more than 14 days) of immunosuppressants or other immunomodulatory drugs for six months before the trial. Treatment with glucocorticosteroids, including in small doses, as well as local use of drugs containing steroids (> 10 mg of prednisolone or its equivalent for more than 14 days before the screening). History of any confirmed or suspected immunosuppressive or immunodeficiency condition. History of splenectomy. History of chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, the gastrointestinal tract, liver, kidneys, hematopoietic or immune systems, mental disease in the acute stage or in the decompensation stage. Transfusion of blood or blood components within 4 months before screening. History of acute and chronic infectious diseases. Consumption of more than 10 units of alcohol per week or history of alcohol addiction, drug addiction or abuse of pharmaceutical products. Smoking of more than 10 cigarettes per day. Participation in another clinical trial within the last 90 days. Pregnancy or lactation. Coagulopathy, hemophilia, bleeding disorder. Participation in stage I of this trial (for volunteers of stage II). Transfusion of COVID-19 convalescent plasma within 14 days before the screening, COVID-19 vaccination less than 30 days before the screening
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Subunit recombinant vaccine for the prevention of coronavirus infection<br>5 volunteers have been vaccinated with a single dose (Stage I) | Biological: Subunit recombinant vaccine for the prevention of coronavirus infection<br>* solution for intramuscular injection, 0.5 ml<br>|
| Experimental: Group 2: Subunit recombinant vaccine for the prevention of coronavirus infection<br>15 volunteers have been vaccinated with a single dose (Stage I) | Biological: Subunit recombinant vaccine for the prevention of coronavirus infection<br>* solution for intramuscular injection, 0.5 ml<br>|
| Experimental: Group 3: Subunit recombinant vaccine for the prevention of coronavirus infection<br>45 volunteers will be vaccinated with the coronavirus vaccine intramuscularly twice (Stage II) | Biological: Subunit recombinant vaccine for the prevention of coronavirus infection<br>* solution for intramuscular injection, 0.5 ml<br>|
| Experimental: Group 4: Subunit recombinant vaccine for the prevention of coronavirus infection<br>45 volunteers have been vaccinated with a single dose of the coronavirus vaccine intramuscularly and then treated with a single dose of placebo (Stage II) | Biological: Subunit recombinant vaccine for the prevention of coronavirus infection<br>* solution for intramuscular injection, 0.5 ml<br>|
| Placebo Comparator: Group 5: Placebo<br>45 volunteers have been vaccinated with placebo intramuscularly twice (Stage II) | Biological: Placebo<br>* solution for intramuscular injection, 0.5 ml<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of actively detected local and systemic AEs (Stage I) | | During 21 days after initial vaccination |
| Incidence of actively detected local and systemic AEs (Stage II) | | During 21 days after initial vaccination |
| Increase in geometric mean titers of antibodies to N-protein of SARS-CoV-2 (Stage II) | Changes from day 0 to days 21 and 42 after the initial vaccination | Days 21 and 42 after the initial vaccination |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of actively detected local AEs | | During 7 days after initial vaccination/revaccination |
| Incidence of actively detected systemic AEs | | During 7 days after initial vaccination/revaccination |
| Incidence of actively detected local AEs | | During 21 days after initial vaccination/revaccination |
| Incidence of actively detected systemic AEs | | During 21 days after initial vaccination/revaccination |
| Incidence of any AEs | | During the trial |
| Number of volunteers hospitalized with COVID-19 | Total number of SARS-CoV-2 infection cases Total number of COVID-19 cases Total number of COVID-19 related deaths | During the trial |
| Proportion SARS-CoV-2 seropositive volunteers | | Day 21 (Stage I and Stage II) and Day 42 (Stage II) |
| Change in IFN-γ, IL-2 and IL-4 levels | | Days 14, 21 (Stage I and Stage II) and Days 28, 42, 90 and 180 (Stage II) after vaccination |
| Change in the subpopulation composition of T-lymphocytes | | Days 14, 21 (Stage I and Stage II) and Days 28, 42, 90 and 180 (Stage II) after vaccination |
| Change in titer of antibodies to N-protein of SARS-CoV-2 | | Days 14, 21 (Stage I and Stage II), Days 28, 42, 90 and 180 (Stage II), Days 240, 350 (Stage II, cohort 2) after initial vaccination |
| Change in the antigen-specific cellular immune response (T-cell response) | | Days 14, 21 (Stage II), Days 28, 42, 90 and 180, Days 240, 350 (Stage II, cohort 2) after initial vaccination |
| Incidence of seroconversion (specific antibodies to N-protein of SARS-CoV-2) | | Days 14, 21 (Stage I and Stage II), Days 28, 42, 90 and 180, Days 240, 350 (Stage II, cohort 2) after initial vaccination |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, COVID, recombinant vaccine, nucleocapsid protein, cellular immunity, SPbSRIVS, Convacell
|
NCT05449158
|
The Relationship Between Left Atrial Pressure and Cardiac Function After Atrioventricular Node Ablation
|
Effects of left atrial pressure-guided ventricular rate changes on cardiac function after atrioventricular node ablation combined with left bundle branch pacing
|
Effects of left atrial pressure-guided ventricular rate changes on cardiac function after atrioventricular node ablation combined with left bundle branch pacing. For patients with non-valvular atrial fibrillation who received atrioventricular node ablation combined with left bundle branch pacing in our hospital, a left atrial pressure catheter was used to monitor atrial pressure during the operation, and a lower average atrial pressure was obtained by adjusting the pacing frequency of the pacemaker. In a randomized controlled manner, the postoperative echocardiography, cardiothoracic ratio, cardiac function, etc. were compared between patients without atrial pressure monitoring and those who received atrial pressure adjustment, in order to clarify the effect of left atrial pressure-guided ventricular rate adjustment on atrioventricular node ablation combined with left bundle Benefit of pacing patients.
|
Effects of Left Atrial Pressure-guided Ventricular Rate Regulation on Cardiac Function in Patients Therapy With Atrioventricular Node Ablation Combined With Left Bundle Branch Pacing
|
Atrial Fibrillation
|
* Procedure: left atrial pressure regulation
|
Inclusion Criteria:~18-85 years old atrial fibrillation patients~Exclusion Criteria:~There is a history of pacemaker implantation; patients after coronary artery bypass grafting; severe coronary stenosis or occlusion cannot be treated with reperfusion;
|
18 Years
|
85 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EF% | aortic vestibular ejection fraction | 1-year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiovascular all-cause mortality | Proportion of patients dying from cardiovascular causes | 1week |
| Hospitalizations for heart failure | Hospitalizations for heart failure | 1 years |
|
Atrial fibrillation;, atrioventricular node ablation;, left bundle branch pacing
|
Atrial Fibrillation, Arrhythmias, Cardiac, Heart Diseases, Cardiovascular Diseases, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LAP Group<br>Control of left atrial pressure changes by adjusting pacemaker frequency | Procedure: left atrial pressure regulation<br>* For patients after atrioventricular node ablation combined with left atrial appendage closure, the regulation of left atrial pressure can be controlled by adjusting the frequency of pacemaker.<br>|
| No Intervention: Control Group<br>General pacemaker rate setting | |
|
The Relationship Between Left Atrial Pressure and Cardiac Function After Atrioventricular Node Ablation
Study Overview
=================
Brief Summary
-----------------
Effects of left atrial pressure-guided ventricular rate changes on cardiac function after atrioventricular node ablation combined with left bundle branch pacing
Detailed Description
-----------------
Effects of left atrial pressure-guided ventricular rate changes on cardiac function after atrioventricular node ablation combined with left bundle branch pacing. For patients with non-valvular atrial fibrillation who received atrioventricular node ablation combined with left bundle branch pacing in our hospital, a left atrial pressure catheter was used to monitor atrial pressure during the operation, and a lower average atrial pressure was obtained by adjusting the pacing frequency of the pacemaker. In a randomized controlled manner, the postoperative echocardiography, cardiothoracic ratio, cardiac function, etc. were compared between patients without atrial pressure monitoring and those who received atrial pressure adjustment, in order to clarify the effect of left atrial pressure-guided ventricular rate adjustment on atrioventricular node ablation combined with left bundle Benefit of pacing patients.
Official Title
-----------------
Effects of Left Atrial Pressure-guided Ventricular Rate Regulation on Cardiac Function in Patients Therapy With Atrioventricular Node Ablation Combined With Left Bundle Branch Pacing
Conditions
-----------------
Atrial Fibrillation
Intervention / Treatment
-----------------
* Procedure: left atrial pressure regulation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-85 years old atrial fibrillation patients Exclusion Criteria: There is a history of pacemaker implantation; patients after coronary artery bypass grafting; severe coronary stenosis or occlusion cannot be treated with reperfusion;
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LAP Group<br>Control of left atrial pressure changes by adjusting pacemaker frequency | Procedure: left atrial pressure regulation<br>* For patients after atrioventricular node ablation combined with left atrial appendage closure, the regulation of left atrial pressure can be controlled by adjusting the frequency of pacemaker.<br>|
| No Intervention: Control Group<br>General pacemaker rate setting | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EF% | aortic vestibular ejection fraction | 1-year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiovascular all-cause mortality | Proportion of patients dying from cardiovascular causes | 1week |
| Hospitalizations for heart failure | Hospitalizations for heart failure | 1 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Atrial fibrillation;, atrioventricular node ablation;, left bundle branch pacing
|
NCT01993160
|
18F-FCH (Fluorocholine)-PET/MR in Staging of High-Risk Prostate Cancer
|
This is a single centre, single arm feasibility study of 18FCH PET-MR imaging for staging patients with high risk prostate cancer.~Study Hypothesis:~FCH-PET/MR will enable more accurate staging of patients with high risk prostate cancer as compared to conventional imaging.
|
Up to 60% of patients treated with radical prostatectomy or external beam radiotherapy for prostate cancer will have biochemical failure at 5 years. This may be due to several reasons, including presence of sub-clinical metastases at time of local therapy.~Currently, patients with high risk prostate cancer are staged by MRI of the prostate (to assess local extent of disease), CT of the abdomen(to detect spread to lymph nodes) and bone scan (to assess for spread to bones). However, these standard imaging exams do not always identify all sites of disease. Recent research has suggested that performing positron emission tomography (PET) scanning with a tracer called fluorocholine (FCH) improves identification of lymph node and bone metastases in prostate cancer, resulting in more accurate diagnosis.~The main goal of this study is to find out whether staging high risk prostate cancer patients with FCH PET-CT and MRI of the whole body will improve detection of primary tumors and metastases compared to current standard imaging exams. Improved staging of patients with prostate cancer may impact patient care as it will help to select more appropriate therapy.~In this study, participants will undergo either combined PET/MRI or PET-CT and MRI after standard evaluations. The accuracy of each staging approach (standard vs. PET and MRI) will be evaluated. In addition, we will incorporate novel methods for data interpretation by creating imaging maps combining data from PET and MRI (termed Multiparametric maps). The goal of this novel approach is to find out whether mapping 2 or more characteristics of a tumor at the same time will improve tumor detection and accuracy of diagnosis.~About 40 men from the Princess Margaret Hospital will take part in this study. The study should take about 2 years to complete enrollment and the results should be known within 36 months of completion of enrollment.
|
18F-FCH-PET/MR in Staging of High-Risk Prostate Cancer: A Multiparametric Approach
|
Prostate Cancer
|
* Drug: Fluorocholine (18F-FCH) Injection
* Radiation: PET scan
* Radiation: Whole body MRI
|
Inclusion Criteria:~Age ≥ 18 years~Histologic diagnosis of carcinoma of prostate~High risk disease: defined as Gleason ≥8, or T3 disease, or PSA >20ng/mL~No prior therapy for prostate cancer (surgery, radiation therapy, hormone therapy, chemotherapy).~Ability to provide written informed consent to participate in the study~Exclusion Criteria:~Prior surgery or radiation therapy for prostate cancer~Prior or ongoing hormone or other systemic therapy for prostate cancer~Inability to lie supine for 90 minutes~Any contraindication to MR as per Joint Department of Medical Imaging policies.~Impaired kidney function with glomerular filtration rate < 30ml/min~Previous anaphylactic reaction to gadolinium or other contraindications to MR.
|
18 Years
|
99 Years
|
Male
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of prostate cancer foci detected with FCH PET/MR compared to MR alone. | | 2 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection rate of lymph node and distant metastases in patients with high risk prostate cancer as compared to conventional imaging strategies (CT abdomen and bone scintigraphy). | | 2 years |
|
Fluorocholine (FCH), Positron emission tomography (PET), Magnetic resonance imaging (MRI)
|
Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms by Site, Neoplasms, Genital Diseases, Male, Genital Diseases, Urogenital Diseases, Prostatic Diseases, Male Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18F-FCH PET MR<br>Integrated whole body PET-MR or PET-CT and separate whole body MRI with use of 18F-FCH as the molecular probe | Drug: Fluorocholine (18F-FCH) Injection<br>* Before the PET-CT scan, the tracer (fluorocholine/FCH) will be injected into a vein in your arm just before the scan. This is the agent we are investigating in this study (not part of the standard procedure)<br>Radiation: PET scan<br>* A whole body PET scan will be performed, integrated with either whole body low dose CT or whole body MRI<br>Radiation: Whole body MRI<br>* A whole body MRI scan will be performed. This may be integrated with PET scan or performed separately.<br>|
|
18F-FCH (Fluorocholine)-PET/MR in Staging of High-Risk Prostate Cancer
Study Overview
=================
Brief Summary
-----------------
This is a single centre, single arm feasibility study of 18FCH PET-MR imaging for staging patients with high risk prostate cancer. Study Hypothesis: FCH-PET/MR will enable more accurate staging of patients with high risk prostate cancer as compared to conventional imaging.
Detailed Description
-----------------
Up to 60% of patients treated with radical prostatectomy or external beam radiotherapy for prostate cancer will have biochemical failure at 5 years. This may be due to several reasons, including presence of sub-clinical metastases at time of local therapy. Currently, patients with high risk prostate cancer are staged by MRI of the prostate (to assess local extent of disease), CT of the abdomen(to detect spread to lymph nodes) and bone scan (to assess for spread to bones). However, these standard imaging exams do not always identify all sites of disease. Recent research has suggested that performing positron emission tomography (PET) scanning with a tracer called fluorocholine (FCH) improves identification of lymph node and bone metastases in prostate cancer, resulting in more accurate diagnosis. The main goal of this study is to find out whether staging high risk prostate cancer patients with FCH PET-CT and MRI of the whole body will improve detection of primary tumors and metastases compared to current standard imaging exams. Improved staging of patients with prostate cancer may impact patient care as it will help to select more appropriate therapy. In this study, participants will undergo either combined PET/MRI or PET-CT and MRI after standard evaluations. The accuracy of each staging approach (standard vs. PET and MRI) will be evaluated. In addition, we will incorporate novel methods for data interpretation by creating imaging maps combining data from PET and MRI (termed Multiparametric maps). The goal of this novel approach is to find out whether mapping 2 or more characteristics of a tumor at the same time will improve tumor detection and accuracy of diagnosis. About 40 men from the Princess Margaret Hospital will take part in this study. The study should take about 2 years to complete enrollment and the results should be known within 36 months of completion of enrollment.
Official Title
-----------------
18F-FCH-PET/MR in Staging of High-Risk Prostate Cancer: A Multiparametric Approach
Conditions
-----------------
Prostate Cancer
Intervention / Treatment
-----------------
* Drug: Fluorocholine (18F-FCH) Injection
* Radiation: PET scan
* Radiation: Whole body MRI
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years Histologic diagnosis of carcinoma of prostate High risk disease: defined as Gleason ≥8, or T3 disease, or PSA >20ng/mL No prior therapy for prostate cancer (surgery, radiation therapy, hormone therapy, chemotherapy). Ability to provide written informed consent to participate in the study Exclusion Criteria: Prior surgery or radiation therapy for prostate cancer Prior or ongoing hormone or other systemic therapy for prostate cancer Inability to lie supine for 90 minutes Any contraindication to MR as per Joint Department of Medical Imaging policies. Impaired kidney function with glomerular filtration rate < 30ml/min Previous anaphylactic reaction to gadolinium or other contraindications to MR.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18F-FCH PET MR<br>Integrated whole body PET-MR or PET-CT and separate whole body MRI with use of 18F-FCH as the molecular probe | Drug: Fluorocholine (18F-FCH) Injection<br>* Before the PET-CT scan, the tracer (fluorocholine/FCH) will be injected into a vein in your arm just before the scan. This is the agent we are investigating in this study (not part of the standard procedure)<br>Radiation: PET scan<br>* A whole body PET scan will be performed, integrated with either whole body low dose CT or whole body MRI<br>Radiation: Whole body MRI<br>* A whole body MRI scan will be performed. This may be integrated with PET scan or performed separately.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of prostate cancer foci detected with FCH PET/MR compared to MR alone. | | 2 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection rate of lymph node and distant metastases in patients with high risk prostate cancer as compared to conventional imaging strategies (CT abdomen and bone scintigraphy). | | 2 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fluorocholine (FCH), Positron emission tomography (PET), Magnetic resonance imaging (MRI)
|
NCT01373203
|
The Role of Fibrocytes in Acute Lung Injury
|
The important character of acute lung injury (ALI) is alveolar capillary membrane damage caused by different diseases, such as sepsis, trauma and shock. One of the important pathological stages is the varying degrees of interstitial fibrosis and semi-permeable alveolar membrane fibrosis. It has been proved that CXCL12/SDF-1 (stromal cell-derived factor-1) induces fibrocyte migration, and promotes fibrosis progression. Study indicated that inhibition of TLR4 receptor signaling pathway improves fibrosis progression induced by ALI, however, the role of fibrocyte in ALI is still unclear. The fibrocytes was significantly increased in asthmatic patients with pulmonary fibrosis, which companies with increased CTGF expression. Therefore, this project assumes that fibrocyte will differentiation to fibroblast/myofibroblast in patient with acute lung injury, which in turn leads to progression of fibrosis. The central hypothesis of this project is that peripheral progenitor cell fibrocytes play an important role in alveolitis caused by acute lung injury. The overall objective of this project is to study the role of fibrocytes in acute lung injury.
|
The Role of Fibrocytes in Acute Lung Injury
|
Acute Lung Injury(ALI)
|
Inclusion Criteria:~Acute Lung Injury patients~Above 20 years old~Bilateral lung infiltrates~PaO2/FiO2<300mmHg~PCWP<18mmHg~Exclusion Criteria:~Pregnant women~Under 20 years old~Hb<8.0mg/dl
|
20 Years
| null | null |
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Acute Lung Injury(ALI)
|
Lung Injury, Acute Lung Injury, Wounds and Injuries, Lung Diseases, Respiratory Tract Diseases, Thoracic Injuries
|
The Role of Fibrocytes in Acute Lung Injury
Study Overview
=================
Brief Summary
-----------------
The important character of acute lung injury (ALI) is alveolar capillary membrane damage caused by different diseases, such as sepsis, trauma and shock. One of the important pathological stages is the varying degrees of interstitial fibrosis and semi-permeable alveolar membrane fibrosis. It has been proved that CXCL12/SDF-1 (stromal cell-derived factor-1) induces fibrocyte migration, and promotes fibrosis progression. Study indicated that inhibition of TLR4 receptor signaling pathway improves fibrosis progression induced by ALI, however, the role of fibrocyte in ALI is still unclear. The fibrocytes was significantly increased in asthmatic patients with pulmonary fibrosis, which companies with increased CTGF expression. Therefore, this project assumes that fibrocyte will differentiation to fibroblast/myofibroblast in patient with acute lung injury, which in turn leads to progression of fibrosis. The central hypothesis of this project is that peripheral progenitor cell fibrocytes play an important role in alveolitis caused by acute lung injury. The overall objective of this project is to study the role of fibrocytes in acute lung injury.
Official Title
-----------------
The Role of Fibrocytes in Acute Lung Injury
Conditions
-----------------
Acute Lung Injury(ALI)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Acute Lung Injury patients Above 20 years old Bilateral lung infiltrates PaO2/FiO2<300mmHg PCWP<18mmHg Exclusion Criteria: Pregnant women Under 20 years old Hb<8.0mg/dl
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute Lung Injury(ALI)
|
|||||
NCT03479996
|
Evaluation of Postoperative Pain After Tension-free Obturator Tape Operation (TVT-O) With or Without Local Anesthetic
|
BACKGROUND:~Compare the pain intensity after TVT-O procedure in the inner part of the thigh where the anesthetic substance will be injected versus the inner part of of the thigh without anesthetic injection in the same woman.~The advantage of this work is that this method of testing neutralizes the effect of pain thresholds of different women.~If an advantage will be found in injecting anesthetic as a reduction in postoperative pain, it could be recommended for all women who undergo surgery of this kind.~METHODS:~Preoperative women will be offered the opportunity to participate in the study after a detailed explanation of the study and determine a date for an elective TVT-O procedure. After signing the Informed Consent Form, they will undergo a TVT-O procedure with injection of anesthetic into one of the obturators membranes. In a random order, Marcaine 5-ml will be injected into a left or right obturator membrane.~One side with Marcaine (Bupivacaine HCL) 0.5% 5 mg / mL Injection,opposite side without injection of any anesthetic.~Before and after surgery, patients will receive Visual Analogue Scale (VAS) instruction and will be polled at the following time points: 1,6,12,24 hours after surgery per inner part of the thigh separately. Each patient will rate the intensity of the pain she feels on the pain questionnaire at each of the time points mentioned before.
|
Evaluation of Postoperative Pain After Tension-free Obturator Tape Operation (TVT-O) With or Without Local Anesthetic
|
Stress Urinary Incontinence
|
* Drug: Marcaine 0.5 % Injectable Solution
|
Inclusion Criteria:~• Women undergoing TVT-O~Exclusion Criteria:~• Repeat surgery
|
35 Years
|
85 Years
|
Female
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leg pain | VAS score | 1 hour after surgery |
| Leg pain | VAS score | 6 hours after surgery |
| Leg pain | VAS score | 12 hours after surgery |
| Leg pain | VAS score | 24 hours after surgery |
|
Bupivacaine, Anesthetics, Anesthetics, Local, Central Nervous System Depressants, Physiological Effects of Drugs, Sensory System Agents, Peripheral Nervous System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anesthetic<br> | Drug: Marcaine 0.5 % Injectable Solution<br>* Intra -operative injection into obturator membrane<br>|
| No Intervention: Control<br> | |
|
Evaluation of Postoperative Pain After Tension-free Obturator Tape Operation (TVT-O) With or Without Local Anesthetic
Study Overview
=================
Brief Summary
-----------------
BACKGROUND: Compare the pain intensity after TVT-O procedure in the inner part of the thigh where the anesthetic substance will be injected versus the inner part of of the thigh without anesthetic injection in the same woman. The advantage of this work is that this method of testing neutralizes the effect of pain thresholds of different women. If an advantage will be found in injecting anesthetic as a reduction in postoperative pain, it could be recommended for all women who undergo surgery of this kind. METHODS: Preoperative women will be offered the opportunity to participate in the study after a detailed explanation of the study and determine a date for an elective TVT-O procedure. After signing the Informed Consent Form, they will undergo a TVT-O procedure with injection of anesthetic into one of the obturators membranes. In a random order, Marcaine 5-ml will be injected into a left or right obturator membrane. One side with Marcaine (Bupivacaine HCL) 0.5% 5 mg / mL Injection,opposite side without injection of any anesthetic. Before and after surgery, patients will receive Visual Analogue Scale (VAS) instruction and will be polled at the following time points: 1,6,12,24 hours after surgery per inner part of the thigh separately. Each patient will rate the intensity of the pain she feels on the pain questionnaire at each of the time points mentioned before.
Official Title
-----------------
Evaluation of Postoperative Pain After Tension-free Obturator Tape Operation (TVT-O) With or Without Local Anesthetic
Conditions
-----------------
Stress Urinary Incontinence
Intervention / Treatment
-----------------
* Drug: Marcaine 0.5 % Injectable Solution
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: • Women undergoing TVT-O Exclusion Criteria: • Repeat surgery
Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 85 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anesthetic<br> | Drug: Marcaine 0.5 % Injectable Solution<br>* Intra -operative injection into obturator membrane<br>|
| No Intervention: Control<br> | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leg pain | VAS score | 1 hour after surgery |
| Leg pain | VAS score | 6 hours after surgery |
| Leg pain | VAS score | 12 hours after surgery |
| Leg pain | VAS score | 24 hours after surgery |
|
|||
NCT05489601
|
Non-intrusive Detection of Temporary Neurologic Impairment by Opioids
|
The investigators aim to prove the feasibility of a non-invasive means to identify temporary neurological impairment resulting from the use of a commonly prescribed opioid by identifying an oculomotor biosignature associated with temporary neurologic impairment in pain-free opioid-naïve subjects, and to initiate the development of such a signature. The investigators also sought to establish the presence of a dose-dependent biosignature for opioid impairment.
|
To determine the detrimental effects of opioid intoxication on normal oculomotor function, the investigators will collect data from up to 25 subjects before and during oxycodone induced intoxication. A within-subjects design will be used, and subjects will be tested under conditions of no dose (placebo), low dose, and high dose. Subjects will be tested during 3 sessions (baseline, placebo, oxycodone); separated by 7 days to allow for complete washout of any drug that was administered. Subjects will perform tests of visual fixation, saccade speed and saccade accuracy, cognitive control over saccades, cognitive control over visual scanning, and visual pursuit. Eye movement data will be collected using an SR Research EyeLink 1000 Plus eye tracking system.~Analysis of the data will be performed by comparing each subject state against the baseline measurements, where baseline represents an unimpaired subject state. Based on prior work with marijuana intoxication, the investigators expect that this data and analysis will successfully reveal a constellation of oculomotor dynamics that can be used to classify whether an individual is or is not currently impaired by oxycodone. Based on published studies, the investigators anticipate these changes will generalize across the opioid class, creating a biosignature of opioid impairment.
|
Prove the Feasibility of a Non-invasive Means to Identify Temporary Neurological Impairment Resulting From the Use of a Commonly Prescribed Opioid by Identifying an Oculomotor Biosignature Associated With Temporary Neurologic Impairment in Pain-free Opioid-naïve Subjects, and to Initiate the Development of Such a Signature.
|
Neurologic Impairment by Opioids
|
* Drug: Oxycodone
|
Inclusion Criteria:~Adults between 21 and 59 years of age.~Males and females; women must practice an effective form of birth control (condoms, diaphragm, birth control pill, IUD).~Exclusion Criteria:~Prior use of any opioids during the preceding 30 days.~Positive urine drug test for any drug at any point during the study.~Pregnancy
|
21 Years
|
59 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eye movement velocity | Eye position over time is recorded and tracked using a specialized eye-tracking camera system during a battery of visual tests under control and oxycodone challenge conditions. This data is converted to a velocity measure as millimeters per second (mm/second) and then converted to an angular velocity as degrees of visual angle per second (dva/second). | 1 hour post-dose for 3 hours across 3 sessions, minimum 48 hours between sessions. |
| Pupil area change | Changes in pupil area are recorded over time using specialized a eye-tracking camera system.~Screen illumination is abruptly changed from dark to maximum brightness and back while the pupils size is measured. The pupil area is represented in the units millimeters squared (mm^2). | 1 hour post-dose for 3 hours across 3 sessions, minimum 48 hours between sessions. |
|
Oxycodone, Analgesics, Opioid, Narcotics, Central Nervous System Depressants, Physiological Effects of Drugs, Analgesics, Sensory System Agents, Peripheral Nervous System Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants<br>Adults between 21 and 59 years of age.~Males and females; women must practice an effective form of birth control (condoms, diaphragm, birth control pill, IUD).~Subjects have taken an opioid prescription for pain management within the prior 24 months and have not used any opioids during the preceding 30 days.~Subjects are required to have a negative urine drug test. At any point during the study, If a subject is found to have a positive drug test, the subject will be discontinued from the study. | Drug: Oxycodone<br>* Oxycodone in 5mg increments up to a maximum of 10mg<br>|
|
Non-intrusive Detection of Temporary Neurologic Impairment by Opioids
Study Overview
=================
Brief Summary
-----------------
The investigators aim to prove the feasibility of a non-invasive means to identify temporary neurological impairment resulting from the use of a commonly prescribed opioid by identifying an oculomotor biosignature associated with temporary neurologic impairment in pain-free opioid-naïve subjects, and to initiate the development of such a signature. The investigators also sought to establish the presence of a dose-dependent biosignature for opioid impairment.
Detailed Description
-----------------
To determine the detrimental effects of opioid intoxication on normal oculomotor function, the investigators will collect data from up to 25 subjects before and during oxycodone induced intoxication. A within-subjects design will be used, and subjects will be tested under conditions of no dose (placebo), low dose, and high dose. Subjects will be tested during 3 sessions (baseline, placebo, oxycodone); separated by 7 days to allow for complete washout of any drug that was administered. Subjects will perform tests of visual fixation, saccade speed and saccade accuracy, cognitive control over saccades, cognitive control over visual scanning, and visual pursuit. Eye movement data will be collected using an SR Research EyeLink 1000 Plus eye tracking system. Analysis of the data will be performed by comparing each subject state against the baseline measurements, where baseline represents an unimpaired subject state. Based on prior work with marijuana intoxication, the investigators expect that this data and analysis will successfully reveal a constellation of oculomotor dynamics that can be used to classify whether an individual is or is not currently impaired by oxycodone. Based on published studies, the investigators anticipate these changes will generalize across the opioid class, creating a biosignature of opioid impairment.
Official Title
-----------------
Prove the Feasibility of a Non-invasive Means to Identify Temporary Neurological Impairment Resulting From the Use of a Commonly Prescribed Opioid by Identifying an Oculomotor Biosignature Associated With Temporary Neurologic Impairment in Pain-free Opioid-naïve Subjects, and to Initiate the Development of Such a Signature.
Conditions
-----------------
Neurologic Impairment by Opioids
Intervention / Treatment
-----------------
* Drug: Oxycodone
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults between 21 and 59 years of age. Males and females; women must practice an effective form of birth control (condoms, diaphragm, birth control pill, IUD). Exclusion Criteria: Prior use of any opioids during the preceding 30 days. Positive urine drug test for any drug at any point during the study. Pregnancy
Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 59 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants<br>Adults between 21 and 59 years of age. Males and females; women must practice an effective form of birth control (condoms, diaphragm, birth control pill, IUD). Subjects have taken an opioid prescription for pain management within the prior 24 months and have not used any opioids during the preceding 30 days. Subjects are required to have a negative urine drug test. At any point during the study, If a subject is found to have a positive drug test, the subject will be discontinued from the study. | Drug: Oxycodone<br>* Oxycodone in 5mg increments up to a maximum of 10mg<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eye movement velocity | Eye position over time is recorded and tracked using a specialized eye-tracking camera system during a battery of visual tests under control and oxycodone challenge conditions. This data is converted to a velocity measure as millimeters per second (mm/second) and then converted to an angular velocity as degrees of visual angle per second (dva/second). | 1 hour post-dose for 3 hours across 3 sessions, minimum 48 hours between sessions. |
| Pupil area change | Changes in pupil area are recorded over time using specialized a eye-tracking camera system. Screen illumination is abruptly changed from dark to maximum brightness and back while the pupils size is measured. The pupil area is represented in the units millimeters squared (mm^2). | 1 hour post-dose for 3 hours across 3 sessions, minimum 48 hours between sessions. |
|
|||
NCT03750864
|
Innovative Approach to Reduce Lung Cancer Stigma
|
This is a feasibility study examining the feasibility and acceptability of a novel psychotherapy intervention on lung cancer patients who are experiencing stigma.
|
Experiences of stigma (perception and internalization of negative appraisal and devaluation from others) are pervasive for lung cancer patients. Previous work has shown associations between lung cancer stigma and detriments in clinically relevant outcomes such as depression, lower quality of life, and reduced engagement in cancer care.~The investigators previously developed Acceptance and Commitment Therapy for Lung Cancer Stigma (ACT-LCS) as a patient-focused intervention to reduce the self-blame, guilt and inhibited disclosure associated with lung cancer stigma. ACT-LCS is based in Acceptance and Commitment Therapy (ACT), a cognitive-behavioral treatment that promotes psychological flexibility through acceptance and valued direction.~This is a feasibility study examining the feasibility and acceptability of ACT-LCS.
|
An Innovative Approach to Reduce Lung Cancer Stigma
|
Lung Cancer Stigma, Lung Cancer, Stigma, Social, Stigmatization, Acceptance Processes
|
* Behavioral: ACT-LCS Therapy
|
Inclusion Criteria:~Proficiency in English~Diagnosed with or treated for Non-Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC) within the prior 12 months.~Scores of 37.5 on the Lung Cancer Stigma Inventory (LCSI) screening measure~Exclusion Criteria:~Not proficient in English
|
18 Years
| null |
All
|
No
|
Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of individuals who consent to the intervention | This measure will be calculated as a function of those eligible and approached who consented to the intervention. It will be utilized as a metric of feasibility and acceptability. | 10 months |
| Number of sessions that each consented patient attended | This measure will be calculated as a count of sessions that each consented participant attended. It will be utilized as a metric of acceptability of the intervention among consented participants. | 10 months |
|
Lung cancer, Stigma, Lung cancer stigma, Acceptance and commitment therapy
|
Lung Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Diseases, Respiratory Tract Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACT-LCS Therapy<br>Intervention is psychosocial counseling utilizing Acceptance and Commitment Therapy for Lung Cancer Stigma (ACT-LCS) as a patient-focused intervention to reduce the self-blame, guilt and inhibited disclosure associated with lung cancer stigma. | Behavioral: ACT-LCS Therapy<br>* All participants in Stage 1, and those randomized to the intervention condition in Stage 2, will receive the Acceptance & Commitment Therapy for Lung Cancer Stigma (ACT-LCS) intervention. The ACT-LC intervention is designed to be delivered as 6 sessions of individual psychotherapy with a trained psychotherapist at a weekly or bimonthly rate, delivered either in person or over the phone. The treatment manual is based in Acceptance and Commitment Therapy (ACT). Therapists are instructed to begin treatment with Module 1. Modules 2-5 can then be administered in any order at the discretion of the therapist, based upon what the therapist thinks is most likely to be helpful to the patient. Module 6 is the final session of treatment.<br>|
|
Innovative Approach to Reduce Lung Cancer Stigma
Study Overview
=================
Brief Summary
-----------------
This is a feasibility study examining the feasibility and acceptability of a novel psychotherapy intervention on lung cancer patients who are experiencing stigma.
Detailed Description
-----------------
Experiences of stigma (perception and internalization of negative appraisal and devaluation from others) are pervasive for lung cancer patients. Previous work has shown associations between lung cancer stigma and detriments in clinically relevant outcomes such as depression, lower quality of life, and reduced engagement in cancer care. The investigators previously developed Acceptance and Commitment Therapy for Lung Cancer Stigma (ACT-LCS) as a patient-focused intervention to reduce the self-blame, guilt and inhibited disclosure associated with lung cancer stigma. ACT-LCS is based in Acceptance and Commitment Therapy (ACT), a cognitive-behavioral treatment that promotes psychological flexibility through acceptance and valued direction. This is a feasibility study examining the feasibility and acceptability of ACT-LCS.
Official Title
-----------------
An Innovative Approach to Reduce Lung Cancer Stigma
Conditions
-----------------
Lung Cancer Stigma, Lung Cancer, Stigma, Social, Stigmatization, Acceptance Processes
Intervention / Treatment
-----------------
* Behavioral: ACT-LCS Therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Proficiency in English Diagnosed with or treated for Non-Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC) within the prior 12 months. Scores of 37.5 on the Lung Cancer Stigma Inventory (LCSI) screening measure Exclusion Criteria: Not proficient in English
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACT-LCS Therapy<br>Intervention is psychosocial counseling utilizing Acceptance and Commitment Therapy for Lung Cancer Stigma (ACT-LCS) as a patient-focused intervention to reduce the self-blame, guilt and inhibited disclosure associated with lung cancer stigma. | Behavioral: ACT-LCS Therapy<br>* All participants in Stage 1, and those randomized to the intervention condition in Stage 2, will receive the Acceptance & Commitment Therapy for Lung Cancer Stigma (ACT-LCS) intervention. The ACT-LC intervention is designed to be delivered as 6 sessions of individual psychotherapy with a trained psychotherapist at a weekly or bimonthly rate, delivered either in person or over the phone. The treatment manual is based in Acceptance and Commitment Therapy (ACT). Therapists are instructed to begin treatment with Module 1. Modules 2-5 can then be administered in any order at the discretion of the therapist, based upon what the therapist thinks is most likely to be helpful to the patient. Module 6 is the final session of treatment.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of individuals who consent to the intervention | This measure will be calculated as a function of those eligible and approached who consented to the intervention. It will be utilized as a metric of feasibility and acceptability. | 10 months |
| Number of sessions that each consented patient attended | This measure will be calculated as a count of sessions that each consented participant attended. It will be utilized as a metric of acceptability of the intervention among consented participants. | 10 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lung cancer, Stigma, Lung cancer stigma, Acceptance and commitment therapy
|
|
NCT02694913
|
Polymorphisms at Distinct Genetic Loci Affect Response to Anti-CD20 Monoclonal Antibody Therapies
|
This is a non-interventional, R01-funded pilot study that will identify serum and cellular markers in patients' blood samples that can be used as short-term biomarkers of rituximab response. We hypothesize that serum complement levels, activation of natural killer cells, and clearance of peripheral B-cells will be accurate biomarkers of rituximab response, and may be correlated with long-term outcomes.
|
This study does not involve the administration of study drug. This study will only require additional blood draws to identify how patients respond to rituximab and other anti-CD20 antibody therapy. It is expected that blood draws will occur on the same day in which an IV is placed to dose you with the anti-CD20 antibody or for other bloodwork being performed in order to avoid extra sticks.~If you take part in this study, you will have additional blood drawn at the following time-points surround anti-CD20 antibody therapy:~Pre Dose, Cycle 1~Two 7.5 ml tubes (two teaspoons) of blood will be taken along with your other pre-chemotherapy bloodwork Post Dose, Cycle 1~Two 5 ml tubes (three teaspoons) of blood will be taken Pre Dose, Cycle 2~Two 5 ml tubes (two teaspoons) of blood will be taken Post Dose, Cycle 2~Two 5 ml tubes (two teaspoons) of blood will be taken Pre Dose, Cycle 6~Two 10 ml tubes (four teaspoons) of blood will be taken Post Dose, Cycle 6~Two 10 ml tubes (four teaspoons) of blood will be taken~Note: Two tubes will be taken at each draw. If no blood was drawn in the prior 8 weeks, 10 ml of blood will be taken per tube. For the first 4 draws (at cycle 1 and cycle 2, pre- and post-), the amount of blood being taken is to ensure that the patient does not have more than 50 ml of blood taken within an 8 week period.
|
Polymorphisms at Distinct Genetic Loci Affect Response to Anti-CD20 Monoclonal Antibody Therapies
|
Lymphoma
|
* Other: Non Interventional
|
Inclusion Criteria:~Any adult patient who has not received rituximab or other anti-CD20 antibody within the past year who is initiating rituximab or other anti-CD20 antibody treatment.~Treatment plan that includes at least two doses of anti-CD20 antibody and longitudinal follow up over at least a one-month time span.~Exclusion Criteria:~Hgb less than 8.0 g/dL or Hct less than 25% (transfusions or growth factors are permissible).~Treatment with any anti-CD20 antibody within the past 12 months.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of peripheral blood mononuclear cells that are B-cells, as measured by flow cytometry for CD19 performed on peripheral blood immediately prior to cycle 2 | | 1 month after the start of treatment |
|
| Intervention/Treatment |
| --- |
|Other: Non Interventional|This is a non therapeutic, pilot study.|
|
Polymorphisms at Distinct Genetic Loci Affect Response to Anti-CD20 Monoclonal Antibody Therapies
Study Overview
=================
Brief Summary
-----------------
This is a non-interventional, R01-funded pilot study that will identify serum and cellular markers in patients' blood samples that can be used as short-term biomarkers of rituximab response. We hypothesize that serum complement levels, activation of natural killer cells, and clearance of peripheral B-cells will be accurate biomarkers of rituximab response, and may be correlated with long-term outcomes.
Detailed Description
-----------------
This study does not involve the administration of study drug. This study will only require additional blood draws to identify how patients respond to rituximab and other anti-CD20 antibody therapy. It is expected that blood draws will occur on the same day in which an IV is placed to dose you with the anti-CD20 antibody or for other bloodwork being performed in order to avoid extra sticks. If you take part in this study, you will have additional blood drawn at the following time-points surround anti-CD20 antibody therapy: Pre Dose, Cycle 1 Two 7.5 ml tubes (two teaspoons) of blood will be taken along with your other pre-chemotherapy bloodwork Post Dose, Cycle 1 Two 5 ml tubes (three teaspoons) of blood will be taken Pre Dose, Cycle 2 Two 5 ml tubes (two teaspoons) of blood will be taken Post Dose, Cycle 2 Two 5 ml tubes (two teaspoons) of blood will be taken Pre Dose, Cycle 6 Two 10 ml tubes (four teaspoons) of blood will be taken Post Dose, Cycle 6 Two 10 ml tubes (four teaspoons) of blood will be taken Note: Two tubes will be taken at each draw. If no blood was drawn in the prior 8 weeks, 10 ml of blood will be taken per tube. For the first 4 draws (at cycle 1 and cycle 2, pre- and post-), the amount of blood being taken is to ensure that the patient does not have more than 50 ml of blood taken within an 8 week period.
Official Title
-----------------
Polymorphisms at Distinct Genetic Loci Affect Response to Anti-CD20 Monoclonal Antibody Therapies
Conditions
-----------------
Lymphoma
Intervention / Treatment
-----------------
* Other: Non Interventional
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Any adult patient who has not received rituximab or other anti-CD20 antibody within the past year who is initiating rituximab or other anti-CD20 antibody treatment. Treatment plan that includes at least two doses of anti-CD20 antibody and longitudinal follow up over at least a one-month time span. Exclusion Criteria: Hgb less than 8.0 g/dL or Hct less than 25% (transfusions or growth factors are permissible). Treatment with any anti-CD20 antibody within the past 12 months.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Other: Non Interventional|This is a non therapeutic, pilot study.|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of peripheral blood mononuclear cells that are B-cells, as measured by flow cytometry for CD19 performed on peripheral blood immediately prior to cycle 2 | | 1 month after the start of treatment |
|
||||
NCT05154227
|
Health@NUS - Studying Health Behaviours and Well-being During the Student-to-Work Life Transition Using mHealth
|
The study aims to investigate body-weight and behavioural trajectories, as well as their underlying individual, social, and environmental determinants from University to early working life. The study employs mHealth approaches in the form of a smartphone app and smart wearables to collect health behaviour and related information to answer the following research questions:~To what extend do health behaviours (activity, diet, and sleep), body weight, and mental well-being change during the transition from university to early working life?~What is the relationship between health behaviours and mental well-being, and how does it differ at different stages of the transition from University to early working life?~What are the determinants of physical activity, healthy eating and sleep in university students and young working adults?~Do these determinants differ at different stages of the student to work life transition?~If so, how do these differences in these determinants relate to changes in health behaviours, weight status, and mental well-being?
|
This is a prospective cohort study. The study period for each participant is 2 years. Participants are required to download the study's smartphone app and wear the assigned smartwatch to collect various information (including step counts and sleep time). Physical measurements are taken in person at baseline, 12 months and 24 months visits. These measurements include height, weight, waist circumference, resting heart rate and blood pressure.~Questionnaires administered at baseline, 12 months and 24 months include:~Demographics (age, gender, religion, socio-economic status, education level)~Personality~Dietary intake and habits~Physical activity, sedentary behavior and screen time~Active and passive transport use~Smoking habit~Sleep quality~Mental health and wellness~Medical history~Women's health-related~Participants will also receive occasional surveys sent to their smartphone through the study app. These surveys will include questions about sleep, diet, technology use, binge drinking, smoking, physical activities and/or emotions.
|
Health@NUS - Studying Health Behaviours and Well-being During the Student-to-Work Life Transition Using mHealth
|
Healthy
|
Inclusion Criteria:~Full time National University of Singapore students (undergraduate and postgraduate)~Singapore Citizen or Permanent Resident;~Has a Singapore registered mobile number• Owns a mobile phone with operating system that is compatible with the study app (iOS 10 or Android 7 and above);~Able to make the upfront deposit of $20 and able to set up the Direct Debit Authorization (DDA) for possible deductions by HPB;~Able to understand the study procedure during the informed consent taking process.~Exclusion Criteria:~Students who will be overseas for more than 6 weeks per trip during the study period (e.g. involved in overseas exchange/internship programmes or stationed overseas) or travelling frequently;~Students who are not able to set up the DDA via online method will be excluded;~Students who has worked in a full-time position for more than a year previously;~Pregnant women will be excluded only at the point of recruitment.
|
18 Years
|
26 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in health behaviours - physical activity | | Baseline, 12 and 24 months follow up |
| Changes in health behaviours - dietary pattern | | Baseline, 12 and 24 months follow up |
| Changes in health behaviours - sleep pattern | | Baseline, 12 and 24 months follow up |
| Changes in health behaviours - mental well-being | | Baseline, 12 and 24 months follow up |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure (mmHG) | | Baseline, 12 and 24 months follow-up |
| Resting heart rate (bpm) | | Baseline, 12 and 24 months follow-up |
| Body Mass Index (kg/m^2) | | Baseline, 12 and 24 months follow-up |
| Waist circumference (cm) | | Baseline, 12 and 24 months follow-up |
|
mhealth, young adults cohort
|
Health@NUS - Studying Health Behaviours and Well-being During the Student-to-Work Life Transition Using mHealth
Study Overview
=================
Brief Summary
-----------------
The study aims to investigate body-weight and behavioural trajectories, as well as their underlying individual, social, and environmental determinants from University to early working life. The study employs mHealth approaches in the form of a smartphone app and smart wearables to collect health behaviour and related information to answer the following research questions: To what extend do health behaviours (activity, diet, and sleep), body weight, and mental well-being change during the transition from university to early working life? What is the relationship between health behaviours and mental well-being, and how does it differ at different stages of the transition from University to early working life? What are the determinants of physical activity, healthy eating and sleep in university students and young working adults? Do these determinants differ at different stages of the student to work life transition? If so, how do these differences in these determinants relate to changes in health behaviours, weight status, and mental well-being?
Detailed Description
-----------------
This is a prospective cohort study. The study period for each participant is 2 years. Participants are required to download the study's smartphone app and wear the assigned smartwatch to collect various information (including step counts and sleep time). Physical measurements are taken in person at baseline, 12 months and 24 months visits. These measurements include height, weight, waist circumference, resting heart rate and blood pressure. Questionnaires administered at baseline, 12 months and 24 months include: Demographics (age, gender, religion, socio-economic status, education level) Personality Dietary intake and habits Physical activity, sedentary behavior and screen time Active and passive transport use Smoking habit Sleep quality Mental health and wellness Medical history Women's health-related Participants will also receive occasional surveys sent to their smartphone through the study app. These surveys will include questions about sleep, diet, technology use, binge drinking, smoking, physical activities and/or emotions.
Official Title
-----------------
Health@NUS - Studying Health Behaviours and Well-being During the Student-to-Work Life Transition Using mHealth
Conditions
-----------------
Healthy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Full time National University of Singapore students (undergraduate and postgraduate) Singapore Citizen or Permanent Resident; Has a Singapore registered mobile number• Owns a mobile phone with operating system that is compatible with the study app (iOS 10 or Android 7 and above); Able to make the upfront deposit of $20 and able to set up the Direct Debit Authorization (DDA) for possible deductions by HPB; Able to understand the study procedure during the informed consent taking process. Exclusion Criteria: Students who will be overseas for more than 6 weeks per trip during the study period (e.g. involved in overseas exchange/internship programmes or stationed overseas) or travelling frequently; Students who are not able to set up the DDA via online method will be excluded; Students who has worked in a full-time position for more than a year previously; Pregnant women will be excluded only at the point of recruitment.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 26 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in health behaviours - physical activity | | Baseline, 12 and 24 months follow up |
| Changes in health behaviours - dietary pattern | | Baseline, 12 and 24 months follow up |
| Changes in health behaviours - sleep pattern | | Baseline, 12 and 24 months follow up |
| Changes in health behaviours - mental well-being | | Baseline, 12 and 24 months follow up |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure (mmHG) | | Baseline, 12 and 24 months follow-up |
| Resting heart rate (bpm) | | Baseline, 12 and 24 months follow-up |
| Body Mass Index (kg/m^2) | | Baseline, 12 and 24 months follow-up |
| Waist circumference (cm) | | Baseline, 12 and 24 months follow-up |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mhealth, young adults cohort
|
||||
NCT03715205
|
Study to Evaluate the Safety of Pembrolizumab in Participants With Unresectable or Metastatic Melanoma or Non-small Cell Lung Cancer in India (MK-3475-593/KEYNOTE-593)
|
This study has been designed to evaluate the safety of pembrolizumab in participants in India with unresectable or metastatic melanoma and participants with non-small cell lung cancer (NSCLC) who are either untreated (programmed cell death ligand 1 [PD-L1] ≥50%) or have experienced disease progression after a platinum-containing systemic therapy (PD-L1 ≥1%).
|
A Prospective, Open-label, Phase 4 Study to Evaluate the Safety of Pembrolizumab (KEYTRUDA®) in Subjects With Unresectable or Metastatic Melanoma or PD-L1 Positive Non-small Cell Lung Cancer (NSCLC) in India (Keynote-593)
|
Carcinoma, Non-Small-Cell Lung, Melanoma
|
* Drug: Pembrolizumab
|
Inclusion Criteria:~Melanoma Participant:~Has a histologically confirmed diagnosis of unresectable Stage III or metastatic melanoma (Stage IV) not amenable to local therapy~Has received no more than 1 line of prior systemic therapy for unresectable Stage III or Stage IV melanoma including mitogen activated protein kinase inhibitors~Has a Lactate Dehydrogenase (LDH) ≤1.5 times ULN~NSCLC Participant-First Line Treatment:~Has a histologically or cytologically confirmed diagnosis of Stage IV NSCLC~Has a tumor that demonstrate PD-L1 strong expression (PD-L1 ≥50%)~Do not have an EGFR sensitizing mutation AND are anaplastic lymphoma kinase (ALK) translocation negative~Has received no systemic anti-cancer therapy for their metastatic NSCLC~NSCLC Participant-Second Line Treatment and Beyond:~Has a histologically or cytologically confirmed diagnosis of stage IIIB//IIIC/IV (including any future updates to the American Joint Committee on Cancer [AJCC] guideline) or recurrent NSCLC~Has a tumor that expresses programmed cell death ligand 1 (PD-L1) ≥1%~Has received prior treatment with at least two cycles of a platinum-containing doublet for Stage IIIB/IV or recurrent disease~Has received an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (either erlotinib, gefitinib, or afatinib) if they have an EGFR sensitizing mutation~Has received crizotinib if they have an ALK translocation~NSCLC participants must also meet the following requirements:~Have a life expectancy of at ≥3 months~Provide a formalin fixed tumor tissue sample for PD-L1 biomarker analysis from a recent biopsy of a tumor lesion not previously irradiated; For first line, biopsies obtained PRIOR to the administration of any systemic therapy administered for the treatment of a tumor (such as neoadjuvant/adjuvant/definitive therapy) will not be permitted for analysis. For second line treatment and beyond, no systemic antineoplastic therapy may be administered between the PD-L1 biopsy and initiating study medication~Have documented evidence of the EGFR mutation status or ALK translocation status. If unable to provide documentation of these molecular changes, formalin-fixed paraffin-embedded tumor tissue of any age should be submitted for testing~Have measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiologist~Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1~Women of childbearing potential (WOCP) must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required~WOCP must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of trial treatment~Men of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy~Exclusion Criteria:~For NSCLC Participant only: Has a tumor specimen that is not evaluable for PD-L1 expression by the laboratory~Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment~Has received prior therapy with an anti- programmed cell death 1 (PD-1), anti-PD-L1, or anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another T-cell receptor (i.e., cytotoxic T-lymphocyte antigen-4 [CTLA-4], OX-40, CD137) or has previously participated in a clinical trial for pembrolizumab (MK-3475)~Has received prior anti-cancer therapy including investigational agent or device within 4 weeks, or completed palliative radiotherapy within 7 days, prior to enrollment~Has recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline~Has recovered adequately from the toxicity and/or complications from major surgery prior to starting trial treatment~Is expected to require any other form of antineoplastic therapy while participating in the trial~Is on systemic corticosteroid therapy within 7 days before the planned date for first dose of treatment or any other form of immunosuppressive medication~Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (exceeding 10 mg daily dose of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment~Has an active autoimmune disease that has required systemic treatment in the past 2 years~Has a known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., cervical cancer in situ, breast carcinoma) that have undergone potentially curative therapy~Has had an allogeneic tissue/solid organ transplant~Has a history of or current radiographically detectable central nervous system metastases and/or carcinomatous meningitis~Has a severe hypersensitivity (≥ Grade 3) to any excipients in pembrolizumab~Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease~Has an active infection requiring systemic therapy including known history of active tuberculosis (Bacillus tuberculosis)~Has a known history of human immunodeficiency virus (HIV) infection~Has a known history of or is positive for hepatitis B (hepatitis B surface antigen [HbsAg] reactive) or hepatitis C (HCV) ribonucleic acid (RNA) [qualitative] is detected~Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial~If participant received prior radiation therapy to a symptomatic metastatic lesion, has recovered to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 1 or Grade 0 AEs due to radiation therapy~Is a regular user of any illicit drug or has a recent history (within the last 3 months) of substance abuse including alcohol~Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment~Has received a live vaccine within 30 days before the first dose of trial treatment~Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) | Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy | From time of signing the informed consent form (ICF) until the end of follow-up (up to approximately 25 months) |
| Incidence of Drug-Related AEs | Percentage of participants experiencing an AE that is determined by the investigator to be related to the treatment | From time of signing the ICF until the end of follow-up (up to approximately 25 months) |
| Incidence of Serious Adverse Events (SAEs) | Percentage of participants experiencing a SAE defined as an AE that did not necessarily have to have a causal relationship to the treatment, that was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was suggested to be significantly detrimental; was a cancer; overdose; or resulted in death | From time of signing the ICF until the end of follow-up (up to approximately 27 months) |
| Incidence of Drug-Related SAEs | Percentage of participants experiencing a SAE that is determined by the investigator to be related to the treatment | From time of signing the ICF until the end of follow-up (up to approximately 27 months) |
| Incidence of Treatment Discontinuations | Percentage of participants discontinuing study drug due to an AE | From time of initiation of study treatment until the end of study treatment (up to approximately 24 months) |
| Incidence of Events of Clinical Interest (ECIs) | Percentage of participants with ECIs including the following: 1) an overdose of pembrolizumab defined as any dose of ≥1000 mg or 2) an elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is ≥3 times the upper limit of normal (ULN) and an elevated total bilirubin lab value that is ≥2 times ULN and, at the same time, an alkaline phosphatase lab value that is <2 times ULN, as determined by way of protocol-specified laboratory testing or unscheduled laboratory testing | From time of signing the ICF until the end of follow-up (up to approximately 27 months) |
|
programmed cell death 1 (PD-1, PD1 ), programmed cell death ligand 1 (PD-L1, PDL1), programmed cell death ligand 2 (PD-L2, PDL2)
|
Pembrolizumab, Antineoplastic Agents, Immunological, Antineoplastic Agents, Immune Checkpoint Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Melanoma<br>Participants with unresectable or metastatic melanoma receive 200 mg of pembrolizumab as an intravenous (IV) infusion every 3 weeks (Q3W) for up to 35 cycles. | Drug: Pembrolizumab<br>* Administered as an intravenous (IV) infusion every 3 weeks (Q3W)<br>* Other names: MK-3475;|
| Experimental: Cohort B: NSCLC<br>Participants with NSCLC who are either treatment naïve or have progressed after prior treatment receive 200 mg of pembrolizumab as an IV infusion every Q3W for up to 35 cycles. | Drug: Pembrolizumab<br>* Administered as an intravenous (IV) infusion every 3 weeks (Q3W)<br>* Other names: MK-3475;|
|
Study to Evaluate the Safety of Pembrolizumab in Participants With Unresectable or Metastatic Melanoma or Non-small Cell Lung Cancer in India (MK-3475-593/KEYNOTE-593)
Study Overview
=================
Brief Summary
-----------------
This study has been designed to evaluate the safety of pembrolizumab in participants in India with unresectable or metastatic melanoma and participants with non-small cell lung cancer (NSCLC) who are either untreated (programmed cell death ligand 1 [PD-L1] ≥50%) or have experienced disease progression after a platinum-containing systemic therapy (PD-L1 ≥1%).
Official Title
-----------------
A Prospective, Open-label, Phase 4 Study to Evaluate the Safety of Pembrolizumab (KEYTRUDA®) in Subjects With Unresectable or Metastatic Melanoma or PD-L1 Positive Non-small Cell Lung Cancer (NSCLC) in India (Keynote-593)
Conditions
-----------------
Carcinoma, Non-Small-Cell Lung, Melanoma
Intervention / Treatment
-----------------
* Drug: Pembrolizumab
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Melanoma Participant: Has a histologically confirmed diagnosis of unresectable Stage III or metastatic melanoma (Stage IV) not amenable to local therapy Has received no more than 1 line of prior systemic therapy for unresectable Stage III or Stage IV melanoma including mitogen activated protein kinase inhibitors Has a Lactate Dehydrogenase (LDH) ≤1.5 times ULN NSCLC Participant-First Line Treatment: Has a histologically or cytologically confirmed diagnosis of Stage IV NSCLC Has a tumor that demonstrate PD-L1 strong expression (PD-L1 ≥50%) Do not have an EGFR sensitizing mutation AND are anaplastic lymphoma kinase (ALK) translocation negative Has received no systemic anti-cancer therapy for their metastatic NSCLC NSCLC Participant-Second Line Treatment and Beyond: Has a histologically or cytologically confirmed diagnosis of stage IIIB//IIIC/IV (including any future updates to the American Joint Committee on Cancer [AJCC] guideline) or recurrent NSCLC Has a tumor that expresses programmed cell death ligand 1 (PD-L1) ≥1% Has received prior treatment with at least two cycles of a platinum-containing doublet for Stage IIIB/IV or recurrent disease Has received an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (either erlotinib, gefitinib, or afatinib) if they have an EGFR sensitizing mutation Has received crizotinib if they have an ALK translocation NSCLC participants must also meet the following requirements: Have a life expectancy of at ≥3 months Provide a formalin fixed tumor tissue sample for PD-L1 biomarker analysis from a recent biopsy of a tumor lesion not previously irradiated; For first line, biopsies obtained PRIOR to the administration of any systemic therapy administered for the treatment of a tumor (such as neoadjuvant/adjuvant/definitive therapy) will not be permitted for analysis. For second line treatment and beyond, no systemic antineoplastic therapy may be administered between the PD-L1 biopsy and initiating study medication Have documented evidence of the EGFR mutation status or ALK translocation status. If unable to provide documentation of these molecular changes, formalin-fixed paraffin-embedded tumor tissue of any age should be submitted for testing Have measurable disease per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiologist Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Women of childbearing potential (WOCP) must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required WOCP must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of trial treatment Men of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy Exclusion Criteria: For NSCLC Participant only: Has a tumor specimen that is not evaluable for PD-L1 expression by the laboratory Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment Has received prior therapy with an anti- programmed cell death 1 (PD-1), anti-PD-L1, or anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another T-cell receptor (i.e., cytotoxic T-lymphocyte antigen-4 [CTLA-4], OX-40, CD137) or has previously participated in a clinical trial for pembrolizumab (MK-3475) Has received prior anti-cancer therapy including investigational agent or device within 4 weeks, or completed palliative radiotherapy within 7 days, prior to enrollment Has recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline Has recovered adequately from the toxicity and/or complications from major surgery prior to starting trial treatment Is expected to require any other form of antineoplastic therapy while participating in the trial Is on systemic corticosteroid therapy within 7 days before the planned date for first dose of treatment or any other form of immunosuppressive medication Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (exceeding 10 mg daily dose of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment Has an active autoimmune disease that has required systemic treatment in the past 2 years Has a known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., cervical cancer in situ, breast carcinoma) that have undergone potentially curative therapy Has had an allogeneic tissue/solid organ transplant Has a history of or current radiographically detectable central nervous system metastases and/or carcinomatous meningitis Has a severe hypersensitivity (≥ Grade 3) to any excipients in pembrolizumab Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease Has an active infection requiring systemic therapy including known history of active tuberculosis (Bacillus tuberculosis) Has a known history of human immunodeficiency virus (HIV) infection Has a known history of or is positive for hepatitis B (hepatitis B surface antigen [HbsAg] reactive) or hepatitis C (HCV) ribonucleic acid (RNA) [qualitative] is detected Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial If participant received prior radiation therapy to a symptomatic metastatic lesion, has recovered to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade 1 or Grade 0 AEs due to radiation therapy Is a regular user of any illicit drug or has a recent history (within the last 3 months) of substance abuse including alcohol Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment Has received a live vaccine within 30 days before the first dose of trial treatment Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Melanoma<br>Participants with unresectable or metastatic melanoma receive 200 mg of pembrolizumab as an intravenous (IV) infusion every 3 weeks (Q3W) for up to 35 cycles. | Drug: Pembrolizumab<br>* Administered as an intravenous (IV) infusion every 3 weeks (Q3W)<br>* Other names: MK-3475;|
| Experimental: Cohort B: NSCLC<br>Participants with NSCLC who are either treatment naïve or have progressed after prior treatment receive 200 mg of pembrolizumab as an IV infusion every Q3W for up to 35 cycles. | Drug: Pembrolizumab<br>* Administered as an intravenous (IV) infusion every 3 weeks (Q3W)<br>* Other names: MK-3475;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) | Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy | From time of signing the informed consent form (ICF) until the end of follow-up (up to approximately 25 months) |
| Incidence of Drug-Related AEs | Percentage of participants experiencing an AE that is determined by the investigator to be related to the treatment | From time of signing the ICF until the end of follow-up (up to approximately 25 months) |
| Incidence of Serious Adverse Events (SAEs) | Percentage of participants experiencing a SAE defined as an AE that did not necessarily have to have a causal relationship to the treatment, that was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was suggested to be significantly detrimental; was a cancer; overdose; or resulted in death | From time of signing the ICF until the end of follow-up (up to approximately 27 months) |
| Incidence of Drug-Related SAEs | Percentage of participants experiencing a SAE that is determined by the investigator to be related to the treatment | From time of signing the ICF until the end of follow-up (up to approximately 27 months) |
| Incidence of Treatment Discontinuations | Percentage of participants discontinuing study drug due to an AE | From time of initiation of study treatment until the end of study treatment (up to approximately 24 months) |
| Incidence of Events of Clinical Interest (ECIs) | Percentage of participants with ECIs including the following: 1) an overdose of pembrolizumab defined as any dose of ≥1000 mg or 2) an elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is ≥3 times the upper limit of normal (ULN) and an elevated total bilirubin lab value that is ≥2 times ULN and, at the same time, an alkaline phosphatase lab value that is <2 times ULN, as determined by way of protocol-specified laboratory testing or unscheduled laboratory testing | From time of signing the ICF until the end of follow-up (up to approximately 27 months) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
programmed cell death 1 (PD-1, PD1 ), programmed cell death ligand 1 (PD-L1, PDL1), programmed cell death ligand 2 (PD-L2, PDL2)
|
||
NCT00662688
|
Chemotherapy With or Without Dalteparin in Treating Patients With Metastatic Pancreatic Cancer
|
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Anticoagulants, such as dalteparin, may help prevent blood clots from forming in patients being treated with chemotherapy. It is not yet known whether gemcitabine is more effective when given alone or together with dalteparin and/or capecitabine in treating patients with pancreatic cancer.~PURPOSE: This randomized phase III trial is studying whether dalteparin prevents blood clots in patients with pancreatic cancer receiving treatment with different combinations of gemcitabine and capecitabine.
|
OBJECTIVES:~Primary~To demonstrate that preventive anticoagulation with dalteparin reduces the number of thromboembolic events.~To determine the number of thromboembolic events occurring with preventive anticoagulation.~Secondary~To determine survival without thrombotic event.~To determine progression-free and overall survival.~To determine time to response of tumor.~To assess tolerance of these regimens.~OUTLINE: This is a multicenter study. Patients are stratified according to participating center and WHO performance status (0-1 vs 2). Patients are randomized to 1 of 4 treatment arms.~Arm A: Patients receive chemotherapy at investigator's discretion~Arm B Patients receive chemotherapy at investigator's discretion and dalteparin In all arms, treatment repeats in the absence of disease progression or unacceptable toxicity.~Blood and plasma samples are obtained at baseline and periodically during study. Blood is examined for biomarkers, resistance to activated protein C, and mutations (Leiden V factor, mutation G20210A, and the factor II gene). Thrombin generation and factors VIIa and VIII are assessed in plasma.~After completion of study therapy, patients are followed periodically.
|
Chemotherapy With or Without Preventive Anticoagulation for Metastatic Cancer of the Pancreas
|
Chemotherapeutic Agent Toxicity, Pancreatic Cancer, Thromboembolism
|
* Drug: daltéparine
* Drug: Chemotherapy at the investigator's discretion
|
DISEASE CHARACTERISTICS:~Histologically confirmed adenocarcinoma of the pancreas~Metastatic disease~Not amenable to treatment~No localized or locally advanced disease~Measurable disease (metastatic or primary tumor) defined as ≥ 2 cm by CT scan or ≥ 1 cm by spiral CT scan or MRI~No progressive thrombo-embolic disease~No adenocarcinoma of the biliary tract or ampulla of Vater~No known CNS metastases~PATIENT CHARACTERISTICS:~WHO performance status 0-2~Life expectancy > 12 weeks~ANC ≥ 1,500/mm^3~Platelet count ≥ 100,000/mm^3~Hemoglobin ≥ 9 g/dL~Alkaline phosphatase < 5 times normal~Bilirubin < 1.5 times normal~Creatinine < 1.5 times normal~Creatinine clearance < 30 mL/min~Pain controlled or stabilized via analgesic therapy~Affiliation with social security system~Not pregnant or nursing~No controlled or uncontrolled jaundice~No contraindication to study drugs~No cardiovascular accident (myocardial infarction, cerebral vascular accident) within the past 6 months~No serious cardiac and/or respiratory disease~No other cancer in the past 5 years except the following cancers, provided they have been completely resected:~Skin cancer~Localized melanoma~Carcinoma in situ of the cervix~No history of thrombophilia~No history of heparin-induced thrombocytopenia~No uncontrolled or persistent hypercalcemia~No psychological, familial, social, and/or geographical condition that precludes participation in the study~PRIOR CONCURRENT THERAPY:~No prior hematologic therapy for metastatic disease~No prior abdominal radiotherapy~No concurrent corticosteroids as anti-emetic therapy~No other concurrent anticoagulation
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thromboembolic events | number of thromboembolic events during anticoagulation treatment | during study treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | | at 6 months |
| Overall survival | | at one year |
| Tolerance of regimens | | each cycle |
|
thromboembolism, chemotherapeutic agent toxicity, adenocarcinoma of the pancreas, stage IV pancreatic cancer, recurrent pancreatic cancer
|
Pancreatic Neoplasms, Thromboembolism, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Endocrine Gland Neoplasms, Digestive System Diseases, Pancreatic Diseases, Endocrine System Diseases, Embolism and Thrombosis, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: chemotherapy<br>chemotherapy at investigator's discretion | Drug: Chemotherapy at the investigator's discretion<br> <br> |
| Experimental: dalteparin<br>dalteparin: 5000 UI sub-cutaneous injection, from Day 1 to Day 28. | Drug: daltéparine<br> <br> Drug: Chemotherapy at the investigator's discretion<br> <br> |
|
Chemotherapy With or Without Dalteparin in Treating Patients With Metastatic Pancreatic Cancer
Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Anticoagulants, such as dalteparin, may help prevent blood clots from forming in patients being treated with chemotherapy. It is not yet known whether gemcitabine is more effective when given alone or together with dalteparin and/or capecitabine in treating patients with pancreatic cancer. PURPOSE: This randomized phase III trial is studying whether dalteparin prevents blood clots in patients with pancreatic cancer receiving treatment with different combinations of gemcitabine and capecitabine.
Detailed Description
-----------------
OBJECTIVES: Primary To demonstrate that preventive anticoagulation with dalteparin reduces the number of thromboembolic events. To determine the number of thromboembolic events occurring with preventive anticoagulation. Secondary To determine survival without thrombotic event. To determine progression-free and overall survival. To determine time to response of tumor. To assess tolerance of these regimens. OUTLINE: This is a multicenter study. Patients are stratified according to participating center and WHO performance status (0-1 vs 2). Patients are randomized to 1 of 4 treatment arms. Arm A: Patients receive chemotherapy at investigator's discretion Arm B Patients receive chemotherapy at investigator's discretion and dalteparin In all arms, treatment repeats in the absence of disease progression or unacceptable toxicity. Blood and plasma samples are obtained at baseline and periodically during study. Blood is examined for biomarkers, resistance to activated protein C, and mutations (Leiden V factor, mutation G20210A, and the factor II gene). Thrombin generation and factors VIIa and VIII are assessed in plasma. After completion of study therapy, patients are followed periodically.
Official Title
-----------------
Chemotherapy With or Without Preventive Anticoagulation for Metastatic Cancer of the Pancreas
Conditions
-----------------
Chemotherapeutic Agent Toxicity, Pancreatic Cancer, Thromboembolism
Intervention / Treatment
-----------------
* Drug: daltéparine
* Drug: Chemotherapy at the investigator's discretion
Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the pancreas Metastatic disease Not amenable to treatment No localized or locally advanced disease Measurable disease (metastatic or primary tumor) defined as ≥ 2 cm by CT scan or ≥ 1 cm by spiral CT scan or MRI No progressive thrombo-embolic disease No adenocarcinoma of the biliary tract or ampulla of Vater No known CNS metastases PATIENT CHARACTERISTICS: WHO performance status 0-2 Life expectancy > 12 weeks ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL Alkaline phosphatase < 5 times normal Bilirubin < 1.5 times normal Creatinine < 1.5 times normal Creatinine clearance < 30 mL/min Pain controlled or stabilized via analgesic therapy Affiliation with social security system Not pregnant or nursing No controlled or uncontrolled jaundice No contraindication to study drugs No cardiovascular accident (myocardial infarction, cerebral vascular accident) within the past 6 months No serious cardiac and/or respiratory disease No other cancer in the past 5 years except the following cancers, provided they have been completely resected: Skin cancer Localized melanoma Carcinoma in situ of the cervix No history of thrombophilia No history of heparin-induced thrombocytopenia No uncontrolled or persistent hypercalcemia No psychological, familial, social, and/or geographical condition that precludes participation in the study PRIOR CONCURRENT THERAPY: No prior hematologic therapy for metastatic disease No prior abdominal radiotherapy No concurrent corticosteroids as anti-emetic therapy No other concurrent anticoagulation
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: chemotherapy<br>chemotherapy at investigator's discretion | Drug: Chemotherapy at the investigator's discretion<br> <br> |
| Experimental: dalteparin<br>dalteparin: 5000 UI sub-cutaneous injection, from Day 1 to Day 28. | Drug: daltéparine<br> <br> Drug: Chemotherapy at the investigator's discretion<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thromboembolic events | number of thromboembolic events during anticoagulation treatment | during study treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | | at 6 months |
| Overall survival | | at one year |
| Tolerance of regimens | | each cycle |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
thromboembolism, chemotherapeutic agent toxicity, adenocarcinoma of the pancreas, stage IV pancreatic cancer, recurrent pancreatic cancer
|
NCT02030938
|
SERI® Surgical Scaffold for Soft Tissue Support in Revision Augmentation Surgery
|
An evaluation of the clinical performance of SERI® Surgical Scaffold for soft tissue support in subjects undergoing revision augmentation surgery for increased nipple to inframammary fold distance.
|
This is a single arm prospective study. Approximately 4 investigational sites will enroll and follow subjects who meet the study criteria.The study will span a total of approximately 18 months: an estimated 6 months for recruitment and 12 months for follow up. 50 subjects will be enrolled in the study. It is anticipated that given an average of 1.5 operated breasts per subject enrolled for Revision Augmentation surgery that 75 implantations of SERI® surgical scaffold will occur.
|
SERI® Surgical Scaffold for Soft Tissue Support in Revision Augmentation Surgery
|
Subjects Requiring Revision Breast Augmentation Surgery
|
* Device: SERI® Surgical Scaffold
|
Inclusion Criteria:~Negative nicotine test at screening visit~Previous augmentation with silicone-filled or saline-filled breast implants requiring Revision Augmentation surgery for increased nipple:inframammary fold distance~Well vascularized skin flaps that can be approximated without tension~Exclusion Criteria:~BMI (Body Mass Index) that is ≥ 30 kg/m2~Active smoker or have smoked within 6 weeks prior to screening visit~Pregnant or nursing~Advanced fibrocystic disease considered to be premalignant without accompanying subcutaneous mastectomy~Carcinoma of the breast~Previous mastectomy or lumpectomy~Abscess or infection in the body at the time of enrollment~Had any disease, including uncontrolled diabetes (e.g., HbAIc > 8%), that is clinically known to impact wound healing ability. For example: collagen-vascular, connective tissue or autoimmune disorders (e.g., Systemic Lupus, Rheumatoid Arthritis, Scleroderma)~Subjects with diagnosed diabetes must have HbAIc ≤ 8% within 3 months of enrollment~Showed tissue characteristics that were clinically incompatible with mammaplasty, such as tissue damage resulting from radiation, inadequate tissue, compromised vascularity or ulceration~Had, or was under treatment for, any condition that may have constituted an unwarranted surgical risk (e.g., unstable cardiac or pulmonary problems)~History of prior implantation of any surgical scaffold (e.g., synthetic mesh, acellular dermal matrix, or biologic mesh) in the breast~Implantation of any non-SERI® surgical scaffold (e.g., synthetic mesh, acellular dermal matrix, or biologic mesh) during the study period~Product contraindications for use of SERI® Surgical Scaffold per the supplied package insert (e.g., hypersensitivity to silk)
|
18 Years
| null |
Female
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reoperation Rate (Per Implanted Breast) for the Presenting Condition at 12 Months. | This refers to the proportion of implanted breasts that will require reoperation for the recurrence of the initial cause of the increase in nipple to inframammary fold distance at the end of the 12-month follow-up period. Reoperation rate outcomes are presented as number of implanted breasts that required a reoperation out of the overall number of units analyzed. | 12 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reoperation Rate (Per Implanted Breast) for Any Cause at 12 Months | This refers to the proportion of implanted breasts that will require reoperation for any cause at the end of the 12 month follow up period. The outcome is presented as the number of implanted breasts that required reoperation from the overall number of units analyzed. | 12 months |
| AE Incidence Rates (Per Implanted Breast) at 30 Days | This refers to the AE incidence rate per implanted breast at thirty days. Outcome is reported as the number of adverse events reported for the overall number of units analyzed. | 30 days |
| AE Incidence Rates (Per Implanted Breast) at 12 Months | This refers to the AE incidence rate per implanted breast at twelve months. Outcome is reported as the number of adverse events reported for the overall number of units analyzed. | 12 months |
| Change in Mammometry From Baseline to 12 Months (Per Implanted Breast) | Mammometry is defined as standardized breast measurements. Mammometry was performed by direct measurement (ie with measuring tape) and indirectly through VECTRA imaging. | 12 months |
| Difference in Mean Scores From Baseline to 12 Months Across 4 Scales of the BREAST Q (Per Patient) | The BREAST-Q is a self-administered questionnaire developed at the Memorial Sloan-Kettering Cancer Center and the University of British Columbia. This instrument specifically measured subject satisfaction and health related quality of life (QoL) following different types of breast surgery (reconstruction,augmentation, reduction, and mastectomy only). A subset of 4 scales from the augmentation module (Satisfaction with breasts, Satisfaction with outcome, Psychosocial wellbeing and Sexual wellbeing) were used in this study.~In accordance with the BREAST-Q manual, subject scores were transformed into linearized measurements on a 0 to 100 scale, using the QScore software which was developed based on the Rasch model. For the transformed scores, a higher score indicated greater satisfaction or higher function. | 12 months |
|
breast implant, revision augmentation, stretch deformity, fold malposition, bottoming out
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SERI® scaffold implanted breasts<br>SERI® Surgical Scaffold is a knitted, multifilament, bioengineered, silk mesh. It is mechanically strong, biocompatible, BIOSILK® purified, and long term bioresorbable. SERI® Surgical Scaffold is a sterile, single use only mesh and is supplied as a 10 x 25 cm sheet. SERI® Surgical Scaffold provides immediate physical and mechanical stabilization of a tissue defect through the strength and porous (scaffold like) construction of its mesh. When long term bioresorption occurs and the patient's own tissue replaces the implanted scaffold over time the mechanical integrity of the repair is maintained.~SERI® Surgical Scaffold is indicated for use as a transitory scaffold for soft tissue support and repair to reinforce deficiencies where weakness or voids exist that require the addition of material to obtain the desired surgical outcome. | Device: SERI® Surgical Scaffold<br>* Standard revision augmentation (with or without implant exchange) with the adjunctive use of SERI® Surgical Scaffold placed intra- or extra-capsularly.<br>|
|
SERI® Surgical Scaffold for Soft Tissue Support in Revision Augmentation Surgery
Study Overview
=================
Brief Summary
-----------------
An evaluation of the clinical performance of SERI® Surgical Scaffold for soft tissue support in subjects undergoing revision augmentation surgery for increased nipple to inframammary fold distance.
Detailed Description
-----------------
This is a single arm prospective study. Approximately 4 investigational sites will enroll and follow subjects who meet the study criteria.The study will span a total of approximately 18 months: an estimated 6 months for recruitment and 12 months for follow up. 50 subjects will be enrolled in the study. It is anticipated that given an average of 1.5 operated breasts per subject enrolled for Revision Augmentation surgery that 75 implantations of SERI® surgical scaffold will occur.
Official Title
-----------------
SERI® Surgical Scaffold for Soft Tissue Support in Revision Augmentation Surgery
Conditions
-----------------
Subjects Requiring Revision Breast Augmentation Surgery
Intervention / Treatment
-----------------
* Device: SERI® Surgical Scaffold
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Negative nicotine test at screening visit Previous augmentation with silicone-filled or saline-filled breast implants requiring Revision Augmentation surgery for increased nipple:inframammary fold distance Well vascularized skin flaps that can be approximated without tension Exclusion Criteria: BMI (Body Mass Index) that is ≥ 30 kg/m2 Active smoker or have smoked within 6 weeks prior to screening visit Pregnant or nursing Advanced fibrocystic disease considered to be premalignant without accompanying subcutaneous mastectomy Carcinoma of the breast Previous mastectomy or lumpectomy Abscess or infection in the body at the time of enrollment Had any disease, including uncontrolled diabetes (e.g., HbAIc > 8%), that is clinically known to impact wound healing ability. For example: collagen-vascular, connective tissue or autoimmune disorders (e.g., Systemic Lupus, Rheumatoid Arthritis, Scleroderma) Subjects with diagnosed diabetes must have HbAIc ≤ 8% within 3 months of enrollment Showed tissue characteristics that were clinically incompatible with mammaplasty, such as tissue damage resulting from radiation, inadequate tissue, compromised vascularity or ulceration Had, or was under treatment for, any condition that may have constituted an unwarranted surgical risk (e.g., unstable cardiac or pulmonary problems) History of prior implantation of any surgical scaffold (e.g., synthetic mesh, acellular dermal matrix, or biologic mesh) in the breast Implantation of any non-SERI® surgical scaffold (e.g., synthetic mesh, acellular dermal matrix, or biologic mesh) during the study period Product contraindications for use of SERI® Surgical Scaffold per the supplied package insert (e.g., hypersensitivity to silk)
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SERI® scaffold implanted breasts<br>SERI® Surgical Scaffold is a knitted, multifilament, bioengineered, silk mesh. It is mechanically strong, biocompatible, BIOSILK® purified, and long term bioresorbable. SERI® Surgical Scaffold is a sterile, single use only mesh and is supplied as a 10 x 25 cm sheet. SERI® Surgical Scaffold provides immediate physical and mechanical stabilization of a tissue defect through the strength and porous (scaffold like) construction of its mesh. When long term bioresorption occurs and the patient's own tissue replaces the implanted scaffold over time the mechanical integrity of the repair is maintained. SERI® Surgical Scaffold is indicated for use as a transitory scaffold for soft tissue support and repair to reinforce deficiencies where weakness or voids exist that require the addition of material to obtain the desired surgical outcome. | Device: SERI® Surgical Scaffold<br>* Standard revision augmentation (with or without implant exchange) with the adjunctive use of SERI® Surgical Scaffold placed intra- or extra-capsularly.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reoperation Rate (Per Implanted Breast) for the Presenting Condition at 12 Months. | This refers to the proportion of implanted breasts that will require reoperation for the recurrence of the initial cause of the increase in nipple to inframammary fold distance at the end of the 12-month follow-up period. Reoperation rate outcomes are presented as number of implanted breasts that required a reoperation out of the overall number of units analyzed. | 12 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reoperation Rate (Per Implanted Breast) for Any Cause at 12 Months | This refers to the proportion of implanted breasts that will require reoperation for any cause at the end of the 12 month follow up period. The outcome is presented as the number of implanted breasts that required reoperation from the overall number of units analyzed. | 12 months |
| AE Incidence Rates (Per Implanted Breast) at 30 Days | This refers to the AE incidence rate per implanted breast at thirty days. Outcome is reported as the number of adverse events reported for the overall number of units analyzed. | 30 days |
| AE Incidence Rates (Per Implanted Breast) at 12 Months | This refers to the AE incidence rate per implanted breast at twelve months. Outcome is reported as the number of adverse events reported for the overall number of units analyzed. | 12 months |
| Change in Mammometry From Baseline to 12 Months (Per Implanted Breast) | Mammometry is defined as standardized breast measurements. Mammometry was performed by direct measurement (ie with measuring tape) and indirectly through VECTRA imaging. | 12 months |
| Difference in Mean Scores From Baseline to 12 Months Across 4 Scales of the BREAST Q (Per Patient) | The BREAST-Q is a self-administered questionnaire developed at the Memorial Sloan-Kettering Cancer Center and the University of British Columbia. This instrument specifically measured subject satisfaction and health related quality of life (QoL) following different types of breast surgery (reconstruction,augmentation, reduction, and mastectomy only). A subset of 4 scales from the augmentation module (Satisfaction with breasts, Satisfaction with outcome, Psychosocial wellbeing and Sexual wellbeing) were used in this study. In accordance with the BREAST-Q manual, subject scores were transformed into linearized measurements on a 0 to 100 scale, using the QScore software which was developed based on the Rasch model. For the transformed scores, a higher score indicated greater satisfaction or higher function. | 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast implant, revision augmentation, stretch deformity, fold malposition, bottoming out
|
|
NCT03710668
|
Gut Microbiota and Parkinson's Disease
|
Over the past decade, experimental data has suggested a complex and bidirectional interaction between the gastrointestinal (GI) tract and the central nervous system (CNS), the so-called Gut- Brain axis. . Changes in the gut microbiota composition may cause alterations in the gut barrier function and intestinal permeability, affecting not only GI epithelial cells and immune system, but also the ENS including both neurons and glial cells . The bidirectional brain-gut-microbiota axis interactions modulate pro- and anti-inflammatory responses. It has been suggested that the gut microbiota changes associated with intestinal inflammation may contribute to the initiation of α-syn misfolding. There is a growing number of evidence confirming that the gut microbiota alterations precede or occur during the course of PD. Importantly, some genetic risk factors may play a crucial role in the interactions between the brain-gut-microbiota axis with respect to gut inflammation. It has been also shown that the methylation status in the SNCA promoter region may affect α-syn expression and the risk for PD. Therefore, a potential role of the gut microbiota as an epigenetic factor influencing DNA methylation may be speculated. Moreover, genetic variant of the component of innate immune system - TREM2 (Triggering Receptor Expressed on Myeloid cells) has been reported to be associated with a higher risk for PD. The ε4 allele of apolipoprotein E (ApoE) has been shown to increase the risk for dementia in synucleinopathies such as PD. Potentially, ApoE genotype, by influencing bile acid secretion, could affect the composition of the gut microbiota to favor the development of organisms triggering misfolding. Moreover, three single nucleotide polymorphisms in CARD15 gene, known to be associated with Crohn's disease, have been also shown to be over-expressed in PD patients, supporting the observation that GI inflammation contributes to the pathogenesis of PD.
|
Normal gut microbiota is essential in preventing colonization of the harmful bacteria by competing with them for vital resources such as food and growth factors .~Another way that gut microbiota can enhance the function of the intestinal barrier is through protecting and improving epithelial tight junctions.~Infection and disease can also briefly affect natural gut flora composition and consequently have harmful effects on the host . Toxins produced by pathogenic microorganisms and the focal inflammation created by immune responses to them can increase gut permeability.~Impaired intestinal barrier function and consequent increased gut permeability can lead to increased translocation of gut bacteria across the intestinal wall and into the mesenteric lymphoid tissue. Furthermore, increased permeability of the gut can also increase the translocation of metabolic products such as lipopolysaccharide (LPS) or neuroactive peptides created by the bacteria that can alter the activity of the enteric nervous system (ENS) and central nervous system (CNS). Increased exposure of the ENS or mucosal immune cells to bacteria can provoke an immune response that can lead to release of inflammatory cytokines and activation of the vagus nerve and spinal afferent neurons. Inflammatory cytokines and the vagal system in turn can modulate the activity of the CNS and ENS.Neuro/immune-active substances derived from the intestinal lumen can penetrate the gut mucosa, be transported by blood, cross the blood-brain-barrier (BBB) and affect the CNS. Gut microbiota can influence CNS function through their ability to synthesize or mimic a range of host-signaling neuroactive molecules, such as acetylcholine (Ach), catecholamines, gamma-aminobutyric acid (GABA), histamine, melatonin and 5-hydroxytryptamine (5-HT, serotonin). 5-HT is crucial in the regulation of of peristalsis or modulation of sensation.~Parkinson's disease (PD) is a multicentric neurodegenerative disorder characterized by the accumulation and aggregation of alfa-synuclein (α-syn) in the substantia nigra in the central nervous system (CNS) and in other neural structures. The classical motor symptoms like bradykinesia, resting tremor, rigidity and late postural instability result from the death of dopamine-generating cells in the substantia nigra. There is also a wide spectrum of non-motor manifestations involving for example olfactory (loss of smell), gastrointestinal (GI), cardiovascular and urogenital systems. It has become evident that the different levels of the brain-gut axis including the autonomic nervous system (ANS) and the enteric nervous system (ENS) may be affected in PD. Recently, it has been also recognized that the brain-gut axis interactions may be essentially influenced by the gut microbiota. On the one hand, dysregulation of the brain-gut-microbiota axis in PD may result in GI dysfunction, which is present in over 80% of PD subjects . On the other hand, this dysregulation may also significantly contribute to the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain .~GUT MICROBIOTA AND PARKINSON'S DISEASE~Over the past decade, experimental data has suggested a complex and bidirectional interaction between the gastrointestinal (GI) tract and the central nervous system (CNS), the so-called Gut- Brain axis. . Changes in the gut microbiota composition may cause alterations in the gut barrier function and intestinal permeability, affecting not only GI epithelial cells and immune system, but also the ENS including both neurons and glial cells . The bidirectional brain-gut-microbiota axis interactions modulate pro- and anti-inflammatory responses. It has been suggested that the gut microbiota changes associated with intestinal inflammation may contribute to the initiation of α-syn misfolding. There is a growing number of evidence confirming that the gut microbiota alterations precede or occur during the course of PD. However, the causal relationship between the microbiota changes and the pathogenesis of PD remains unclear.~The interesting concept of molecular mimicry involving the microbiota in neurodegeneration has been also proposed. Indeed, Friedland suggested that bacterial proteins may elicit cross-seeded misfolding, inflammation and oxidative stress, and cellular toxicity in neurodegeneration, initiating or otherwise influencing the development of PD, Alzheimer's disease and other related disorders. Pathways of molecular mimicry processes induced by bacterial amyloid may involve TLR2/1, C14, and NFκB among others. Priming of the innate immune system by the microbiota (residing in the gut and oral/nasal cavities) may enhance the inflammatory response to cerebral amyloids such as α-syn. Trudler et al postulated that cerebral amyloid may mimic viral or bacterial infection resulting in glial cell activation through TLRs. Specifically, it has been documented that neuroinflammation in PD is associated with upregulation of TLR2 signaling and activation of microglia. TLR2, playing an important role in the regulation of intestinal barrier integrity, has been also found to activate microglial cells in the CNS. It has been suggested that the peripheral immune response characterized by the presence of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-8 in the serum induces a disruption of the blood-brain barrier and promotes microglia-mediated inflammation and neurotoxicity. In a germ-free animal model, it has been found that the gut microbiota influences the blood-brain barrier permeability associated with reduced expression of the tight junction proteins in a homological way as it affects the intestinal epithelial barrier. Very recently, Sui et al proved that a bidirectional transport of α-syn into and out of the brain by the blood-brain barrier is possible and suggested that LPS-induced inflammation could increase α-syn uptake by the brain by disrupting the blood-brain barrier.~In an animal model of PD, peripherally-induced inflammation was shown to induce the microglial complement pathway to damage dopaminergic neurons. Several studies have demonstrated that pro-inflammatory factors associated with chronic GI diseases induce brain inflammation and the death of dopaminergic neurons and could eventually be responsible for parkinsonism.~Importantly, some genetic risk factors may play a crucial role in the interactions between the brain-gut-microbiota axis with respect to gut inflammation. It has been also shown that the methylation status in the SNCA promoter region may affect α-syn expression and the risk for PD. Therefore, a potential role of the gut microbiota as an epigenetic factor influencing DNA methylation may be speculated. Moreover, genetic variant of the component of innate immune system - TREM2 (Triggering Receptor Expressed on Myeloid cells) has been reported to be associated with a higher risk for PD. The ε4 allele of apolipoprotein E (ApoE) has been shown to increase the risk for dementia in synucleinopathies such as PD. Potentially, ApoE genotype, by influencing bile acid secretion, could affect the composition of the gut microbiota to favor the development of organisms triggering misfolding. Moreover, three single nucleotide polymorphisms in CARD15 gene, known to be associated with Crohn's disease, have been also shown to be over-expressed in PD patients, supporting the observation that GI inflammation contributes to the pathogenesis of PD.
|
Gut Microbiota and Parkinson's Disease
|
Parkinson Disease
|
* Radiation: MRI if indicated
|
Inclusion Criteria:~(50) patients diagnosed with Parkinson's Disease .~(50) Control group free from Disease .~Exclusion Criteria:~prior surgeries.~any patients or controls currently taking antibiotics or probiotic supplements.~having a known history of disease with an disease such, autoimmune disorders , cardiac patients~history of stroke ,rheumatoid arthritis, type-1-diabetes, and IBD .
|
50 Years
|
70 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of gut microbiota on pathogenesis of Parkinson's diseases | the QIAamp DNA Stool mini kit to extract total bactria DNA Some genetic risk factors may play a crucial role in the interactions between the brain-gut-microbiota axis with respect to gut inflammation. It has been also shown that the methylation status in the SNCA promoter region may affect α-syn expression and the risk for PD | 1 year |
|
Parkinson Disease, Parkinsonian Disorders, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Synucleinopathies, Neurodegenerative Diseases
|
| Intervention/Treatment |
| --- |
|Radiation: MRI if indicated|MRI brain if indicated|
|
Gut Microbiota and Parkinson's Disease
Study Overview
=================
Brief Summary
-----------------
Over the past decade, experimental data has suggested a complex and bidirectional interaction between the gastrointestinal (GI) tract and the central nervous system (CNS), the so-called Gut- Brain axis. . Changes in the gut microbiota composition may cause alterations in the gut barrier function and intestinal permeability, affecting not only GI epithelial cells and immune system, but also the ENS including both neurons and glial cells . The bidirectional brain-gut-microbiota axis interactions modulate pro- and anti-inflammatory responses. It has been suggested that the gut microbiota changes associated with intestinal inflammation may contribute to the initiation of α-syn misfolding. There is a growing number of evidence confirming that the gut microbiota alterations precede or occur during the course of PD. Importantly, some genetic risk factors may play a crucial role in the interactions between the brain-gut-microbiota axis with respect to gut inflammation. It has been also shown that the methylation status in the SNCA promoter region may affect α-syn expression and the risk for PD. Therefore, a potential role of the gut microbiota as an epigenetic factor influencing DNA methylation may be speculated. Moreover, genetic variant of the component of innate immune system - TREM2 (Triggering Receptor Expressed on Myeloid cells) has been reported to be associated with a higher risk for PD. The ε4 allele of apolipoprotein E (ApoE) has been shown to increase the risk for dementia in synucleinopathies such as PD. Potentially, ApoE genotype, by influencing bile acid secretion, could affect the composition of the gut microbiota to favor the development of organisms triggering misfolding. Moreover, three single nucleotide polymorphisms in CARD15 gene, known to be associated with Crohn's disease, have been also shown to be over-expressed in PD patients, supporting the observation that GI inflammation contributes to the pathogenesis of PD.
Detailed Description
-----------------
Normal gut microbiota is essential in preventing colonization of the harmful bacteria by competing with them for vital resources such as food and growth factors . Another way that gut microbiota can enhance the function of the intestinal barrier is through protecting and improving epithelial tight junctions. Infection and disease can also briefly affect natural gut flora composition and consequently have harmful effects on the host . Toxins produced by pathogenic microorganisms and the focal inflammation created by immune responses to them can increase gut permeability. Impaired intestinal barrier function and consequent increased gut permeability can lead to increased translocation of gut bacteria across the intestinal wall and into the mesenteric lymphoid tissue. Furthermore, increased permeability of the gut can also increase the translocation of metabolic products such as lipopolysaccharide (LPS) or neuroactive peptides created by the bacteria that can alter the activity of the enteric nervous system (ENS) and central nervous system (CNS). Increased exposure of the ENS or mucosal immune cells to bacteria can provoke an immune response that can lead to release of inflammatory cytokines and activation of the vagus nerve and spinal afferent neurons. Inflammatory cytokines and the vagal system in turn can modulate the activity of the CNS and ENS.Neuro/immune-active substances derived from the intestinal lumen can penetrate the gut mucosa, be transported by blood, cross the blood-brain-barrier (BBB) and affect the CNS. Gut microbiota can influence CNS function through their ability to synthesize or mimic a range of host-signaling neuroactive molecules, such as acetylcholine (Ach), catecholamines, gamma-aminobutyric acid (GABA), histamine, melatonin and 5-hydroxytryptamine (5-HT, serotonin). 5-HT is crucial in the regulation of of peristalsis or modulation of sensation. Parkinson's disease (PD) is a multicentric neurodegenerative disorder characterized by the accumulation and aggregation of alfa-synuclein (α-syn) in the substantia nigra in the central nervous system (CNS) and in other neural structures. The classical motor symptoms like bradykinesia, resting tremor, rigidity and late postural instability result from the death of dopamine-generating cells in the substantia nigra. There is also a wide spectrum of non-motor manifestations involving for example olfactory (loss of smell), gastrointestinal (GI), cardiovascular and urogenital systems. It has become evident that the different levels of the brain-gut axis including the autonomic nervous system (ANS) and the enteric nervous system (ENS) may be affected in PD. Recently, it has been also recognized that the brain-gut axis interactions may be essentially influenced by the gut microbiota. On the one hand, dysregulation of the brain-gut-microbiota axis in PD may result in GI dysfunction, which is present in over 80% of PD subjects . On the other hand, this dysregulation may also significantly contribute to the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain . GUT MICROBIOTA AND PARKINSON'S DISEASE Over the past decade, experimental data has suggested a complex and bidirectional interaction between the gastrointestinal (GI) tract and the central nervous system (CNS), the so-called Gut- Brain axis. . Changes in the gut microbiota composition may cause alterations in the gut barrier function and intestinal permeability, affecting not only GI epithelial cells and immune system, but also the ENS including both neurons and glial cells . The bidirectional brain-gut-microbiota axis interactions modulate pro- and anti-inflammatory responses. It has been suggested that the gut microbiota changes associated with intestinal inflammation may contribute to the initiation of α-syn misfolding. There is a growing number of evidence confirming that the gut microbiota alterations precede or occur during the course of PD. However, the causal relationship between the microbiota changes and the pathogenesis of PD remains unclear. The interesting concept of molecular mimicry involving the microbiota in neurodegeneration has been also proposed. Indeed, Friedland suggested that bacterial proteins may elicit cross-seeded misfolding, inflammation and oxidative stress, and cellular toxicity in neurodegeneration, initiating or otherwise influencing the development of PD, Alzheimer's disease and other related disorders. Pathways of molecular mimicry processes induced by bacterial amyloid may involve TLR2/1, C14, and NFκB among others. Priming of the innate immune system by the microbiota (residing in the gut and oral/nasal cavities) may enhance the inflammatory response to cerebral amyloids such as α-syn. Trudler et al postulated that cerebral amyloid may mimic viral or bacterial infection resulting in glial cell activation through TLRs. Specifically, it has been documented that neuroinflammation in PD is associated with upregulation of TLR2 signaling and activation of microglia. TLR2, playing an important role in the regulation of intestinal barrier integrity, has been also found to activate microglial cells in the CNS. It has been suggested that the peripheral immune response characterized by the presence of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-8 in the serum induces a disruption of the blood-brain barrier and promotes microglia-mediated inflammation and neurotoxicity. In a germ-free animal model, it has been found that the gut microbiota influences the blood-brain barrier permeability associated with reduced expression of the tight junction proteins in a homological way as it affects the intestinal epithelial barrier. Very recently, Sui et al proved that a bidirectional transport of α-syn into and out of the brain by the blood-brain barrier is possible and suggested that LPS-induced inflammation could increase α-syn uptake by the brain by disrupting the blood-brain barrier. In an animal model of PD, peripherally-induced inflammation was shown to induce the microglial complement pathway to damage dopaminergic neurons. Several studies have demonstrated that pro-inflammatory factors associated with chronic GI diseases induce brain inflammation and the death of dopaminergic neurons and could eventually be responsible for parkinsonism. Importantly, some genetic risk factors may play a crucial role in the interactions between the brain-gut-microbiota axis with respect to gut inflammation. It has been also shown that the methylation status in the SNCA promoter region may affect α-syn expression and the risk for PD. Therefore, a potential role of the gut microbiota as an epigenetic factor influencing DNA methylation may be speculated. Moreover, genetic variant of the component of innate immune system - TREM2 (Triggering Receptor Expressed on Myeloid cells) has been reported to be associated with a higher risk for PD. The ε4 allele of apolipoprotein E (ApoE) has been shown to increase the risk for dementia in synucleinopathies such as PD. Potentially, ApoE genotype, by influencing bile acid secretion, could affect the composition of the gut microbiota to favor the development of organisms triggering misfolding. Moreover, three single nucleotide polymorphisms in CARD15 gene, known to be associated with Crohn's disease, have been also shown to be over-expressed in PD patients, supporting the observation that GI inflammation contributes to the pathogenesis of PD.
Official Title
-----------------
Gut Microbiota and Parkinson's Disease
Conditions
-----------------
Parkinson Disease
Intervention / Treatment
-----------------
* Radiation: MRI if indicated
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: (50) patients diagnosed with Parkinson's Disease . (50) Control group free from Disease . Exclusion Criteria: prior surgeries. any patients or controls currently taking antibiotics or probiotic supplements. having a known history of disease with an disease such, autoimmune disorders , cardiac patients history of stroke ,rheumatoid arthritis, type-1-diabetes, and IBD .
Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Radiation: MRI if indicated|MRI brain if indicated|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of gut microbiota on pathogenesis of Parkinson's diseases | the QIAamp DNA Stool mini kit to extract total bactria DNA Some genetic risk factors may play a crucial role in the interactions between the brain-gut-microbiota axis with respect to gut inflammation. It has been also shown that the methylation status in the SNCA promoter region may affect α-syn expression and the risk for PD | 1 year |
|
|||
NCT05084755
|
VAXZEVRIA Japan Post-Marketing Surveillance (PMS) for the Subjects With Underlying Disease at High-risk for Worsening COVID-19
|
To provide more information on safety profile of VAXZEVRIA in Japanese subjects, specific drug use result study in subjects with underling disease at higher risk of worsening COVID-19 is planned as an additional pharmacovigilance plan.~The present study aims to collect information on adverse drug reactions or COVID-19 infection after VAXZEVRIA vaccination and to evaluate the safety of this vaccine.
|
To provide more information on safety profile of VAXZEVRIA in Japanese subjects, specific drug use result study in subjects with underling disease at higher risk of worsening COVID-19 is planned as an additional pharmacovigilance plan.~The present study aims to collect information on adverse drug reactions (local/systemic reactions), adverse events (including Shock/ Anaphylaxis, Thrombosis in combination with thrombocytopenia, Immune-mediated neurological conditions ,Vaccine-associated enhanced disease(VAED) including Vaccine-associated enhanced respiratory disease(VAERD) and Thrombosis) or COVID-19 infection after VAXZEVRIA vaccination and to evaluate the safety of this vaccine
|
VAXZEVRIA Intramuscular Injection Specific Use Result Study for the Subjects With Underlying Disease at High-risk for Worsening COVID-19
|
Prevention of Infectious Disease Caused by SARS-CoV-2
|
Inclusion Criteria:~The subjects with underlying disease at high-risk for worsening COVID-19.~The adults (in the case of a minor aged less than 20 years, the parent or the legal guardian) who are able to enter their symptoms in the health observation diary and who have been fully informed and have given written consent to the use of the needed information to be part of the observational study.~Exclusion Criteria:~None
| null | null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse drug reactions, its incidence (%) (number of adverse drug reaction/number of eligible safety analysis population) will be calculated by preferred term (PT). | Adverse events that the investigator could not deny the causal relationship with VAXZEVRIA will be treated as adverse drug reactions. Number of adverse drug reactions, its incidence (%) (number of adverse drug reaction/number of eligible safety analysis population) will be calculated by preferred term (PT). | from the first vaccination date to 28 days after the second vaccination date |
| Number of local/systemic reactions and its incidence (%) will be calculated for each reaction and also by grade. Ad hoc analysis might be performed as necessary. | Local/systemic reactions recorded in health observation diary by subjects and entered by the investigator in eCRF will be treated as specific adverse events and number of local/systemic reactions and its incidence (%) will be calculated for each reaction and also by grade. Ad hoc analysis might be performed as necessary. | each vaccination day (Day 1) to Day 8 |
| Number of the subjects considered to be severe case of COVID-19 and its incidence (%) will be calculated. The subject who required a hospitalization in intensive care unit or use of respirator will be defined as a severe case. | Number of the subjects considered to be severe case of COVID-19 and its incidence (%) will be calculated. The subject who required a hospitalization in intensive care unit or use of respirator will be defined as a severe case based on the severity classification reference of A guide for front-line healthcare workers (MHLW, 2020). Ad hoc analysis might be performed as necessary. | from the first vaccination date to 28 days after the second vaccination date |
|
Communicable Diseases, Infections, COVID-19, Disease Attributes, Pathologic Processes, Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Virus Diseases, Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases
|
VAXZEVRIA Japan Post-Marketing Surveillance (PMS) for the Subjects With Underlying Disease at High-risk for Worsening COVID-19
Study Overview
=================
Brief Summary
-----------------
To provide more information on safety profile of VAXZEVRIA in Japanese subjects, specific drug use result study in subjects with underling disease at higher risk of worsening COVID-19 is planned as an additional pharmacovigilance plan. The present study aims to collect information on adverse drug reactions or COVID-19 infection after VAXZEVRIA vaccination and to evaluate the safety of this vaccine.
Detailed Description
-----------------
To provide more information on safety profile of VAXZEVRIA in Japanese subjects, specific drug use result study in subjects with underling disease at higher risk of worsening COVID-19 is planned as an additional pharmacovigilance plan. The present study aims to collect information on adverse drug reactions (local/systemic reactions), adverse events (including Shock/ Anaphylaxis, Thrombosis in combination with thrombocytopenia, Immune-mediated neurological conditions ,Vaccine-associated enhanced disease(VAED) including Vaccine-associated enhanced respiratory disease(VAERD) and Thrombosis) or COVID-19 infection after VAXZEVRIA vaccination and to evaluate the safety of this vaccine
Official Title
-----------------
VAXZEVRIA Intramuscular Injection Specific Use Result Study for the Subjects With Underlying Disease at High-risk for Worsening COVID-19
Conditions
-----------------
Prevention of Infectious Disease Caused by SARS-CoV-2
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subjects with underlying disease at high-risk for worsening COVID-19. The adults (in the case of a minor aged less than 20 years, the parent or the legal guardian) who are able to enter their symptoms in the health observation diary and who have been fully informed and have given written consent to the use of the needed information to be part of the observational study. Exclusion Criteria: None
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse drug reactions, its incidence (%) (number of adverse drug reaction/number of eligible safety analysis population) will be calculated by preferred term (PT). | Adverse events that the investigator could not deny the causal relationship with VAXZEVRIA will be treated as adverse drug reactions. Number of adverse drug reactions, its incidence (%) (number of adverse drug reaction/number of eligible safety analysis population) will be calculated by preferred term (PT). | from the first vaccination date to 28 days after the second vaccination date |
| Number of local/systemic reactions and its incidence (%) will be calculated for each reaction and also by grade. Ad hoc analysis might be performed as necessary. | Local/systemic reactions recorded in health observation diary by subjects and entered by the investigator in eCRF will be treated as specific adverse events and number of local/systemic reactions and its incidence (%) will be calculated for each reaction and also by grade. Ad hoc analysis might be performed as necessary. | each vaccination day (Day 1) to Day 8 |
| Number of the subjects considered to be severe case of COVID-19 and its incidence (%) will be calculated. The subject who required a hospitalization in intensive care unit or use of respirator will be defined as a severe case. | Number of the subjects considered to be severe case of COVID-19 and its incidence (%) will be calculated. The subject who required a hospitalization in intensive care unit or use of respirator will be defined as a severe case based on the severity classification reference of A guide for front-line healthcare workers (MHLW, 2020). Ad hoc analysis might be performed as necessary. | from the first vaccination date to 28 days after the second vaccination date |
|
|||||
NCT01533909
|
Development of a Screening Tool to Detect and Stage Cachectic Cancer Patients
|
The aim of the study is to develop a screenings tool that will enable hospital nurses to detect and stage cancer cachectic patients. The early detection and staging of cancer cachexia will assist the oncology team in providing the cachectic cancer patient tailor-made patient care.
|
In this cross-sectional study, the participants will complete 4 times a set of questionnaires and measurements. The data that will be collected is:~age; sex; height; weight; type of tumour; classification of malignant tumours (TNM); progression of tumour and used therapy; blood sample to analyse albumin, creatine, hemoglobin, LDH and CRP; use of parental nutrition; dietary assessment; use of nutritional supplements; Quality of Life by using the EORTC-QlQ; Subjective Global Assessment; presence of Percutaneous endoscopic gastrostomy; use of enteral or parenteral nutrition; body composition based on a Bio Impedance Assessment; hand grip strength and mid upper arm circumference. Based on all these data points a easy to use tool/score for a hospital setting will be created. During the first assessment the measurements will be done in the morning and the evening to test the reproducibility.
|
Development of a Screening Tool to Detect and Stage Cachectic Cancer Patients
|
Cachexia
|
Inclusion Criteria:~New Diagnosed Patients With Primary Head and Neck Cancer Neoplasms~New Diagnosed Patients With Metastatic Pancreatic Neoplasms~New Diagnosed Patients With Metastatic Colonic Neoplasms~Exclusion Criteria:~Patients With Other Primary Neoplasms~Patients Already in Therapy~Patients With Non-metastatic Colonic or Pancreatic Neoplasms
|
18 Years
|
95 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutritional Assessment | Patient-Generated Subjective Global Assessment Instrument is a measure for the nutritional status of the participants. The final score of this instruments devides participants into three categories: well-nourished, moderately nourished or suspected malnourished. | 4 times in 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | The EORTC-QlQ questionnaire will be used to assess the quality of life of the participants. | 4 times in 6 months |
| Anthropometric measurements | Mid-upper arm circumference will be measured to have an idea of the muscle mass.~Hand Grip Strength will be measured to obtain an idea of the muscle strength. Weight will be measured during every occasion. Question will be asked about weight loss during the last 6 months. Body composition will be measured by Bio-impedance assessment to obtain an indication of the fat-free mass.~Changes of all these measurements will be monitored. | 4 times in 6 months |
| Markers of inflammation/metabolic disturbance | Biomarkers will be selected as part of the routine hospital assessment. These markers are C-reactief proteïne, albumin, creatinin, hemoglobin and Lactate dehydrogenase (LDH). These markers are a measure of the nutritional status and are seen as markers for the catabolic state of cachectic cancer patients. | 4 times in 6 months |
|
Cachexia, Weight Loss, Body Weight Changes, Body Weight, Thinness
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cancer patients<br>As this is not an intervention study there is only one cohort. Patients that will be included and excluded are described in the eligibility section. | |
|
Development of a Screening Tool to Detect and Stage Cachectic Cancer Patients
Study Overview
=================
Brief Summary
-----------------
The aim of the study is to develop a screenings tool that will enable hospital nurses to detect and stage cancer cachectic patients. The early detection and staging of cancer cachexia will assist the oncology team in providing the cachectic cancer patient tailor-made patient care.
Detailed Description
-----------------
In this cross-sectional study, the participants will complete 4 times a set of questionnaires and measurements. The data that will be collected is: age; sex; height; weight; type of tumour; classification of malignant tumours (TNM); progression of tumour and used therapy; blood sample to analyse albumin, creatine, hemoglobin, LDH and CRP; use of parental nutrition; dietary assessment; use of nutritional supplements; Quality of Life by using the EORTC-QlQ; Subjective Global Assessment; presence of Percutaneous endoscopic gastrostomy; use of enteral or parenteral nutrition; body composition based on a Bio Impedance Assessment; hand grip strength and mid upper arm circumference. Based on all these data points a easy to use tool/score for a hospital setting will be created. During the first assessment the measurements will be done in the morning and the evening to test the reproducibility.
Official Title
-----------------
Development of a Screening Tool to Detect and Stage Cachectic Cancer Patients
Conditions
-----------------
Cachexia
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: New Diagnosed Patients With Primary Head and Neck Cancer Neoplasms New Diagnosed Patients With Metastatic Pancreatic Neoplasms New Diagnosed Patients With Metastatic Colonic Neoplasms Exclusion Criteria: Patients With Other Primary Neoplasms Patients Already in Therapy Patients With Non-metastatic Colonic or Pancreatic Neoplasms
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 95 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cancer patients<br>As this is not an intervention study there is only one cohort. Patients that will be included and excluded are described in the eligibility section. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutritional Assessment | Patient-Generated Subjective Global Assessment Instrument is a measure for the nutritional status of the participants. The final score of this instruments devides participants into three categories: well-nourished, moderately nourished or suspected malnourished. | 4 times in 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | The EORTC-QlQ questionnaire will be used to assess the quality of life of the participants. | 4 times in 6 months |
| Anthropometric measurements | Mid-upper arm circumference will be measured to have an idea of the muscle mass. Hand Grip Strength will be measured to obtain an idea of the muscle strength. Weight will be measured during every occasion. Question will be asked about weight loss during the last 6 months. Body composition will be measured by Bio-impedance assessment to obtain an indication of the fat-free mass. Changes of all these measurements will be monitored. | 4 times in 6 months |
| Markers of inflammation/metabolic disturbance | Biomarkers will be selected as part of the routine hospital assessment. These markers are C-reactief proteïne, albumin, creatinin, hemoglobin and Lactate dehydrogenase (LDH). These markers are a measure of the nutritional status and are seen as markers for the catabolic state of cachectic cancer patients. | 4 times in 6 months |
|
|||
NCT00506246
|
Efficacy and Safety Study of Two Propofol Formulations
|
The purpose of the study to compare Propofol-MCT/LCT with LCT in terms of their efficacy and safety during total intravenous anaesthesia
|
Propofol (chemical substance 2, 6-Diisopropylphenol) is a short-acting intravenous general anaesthetic which is used for induction and maintenance of a general anaesthesia, for long-term sedation of ventilated intensive care patients or for short-term sedation in diagnostic and surgical procedures. As an active substance propofol produces good and readily controlled anaesthesia with smooth and problem-free recovery both in adult patients and in children over 1 month of age. One potential advantage of this formulation is that the MCT/LCT-emulsion reduces pain on injection, a frequently reported adverse reaction with LCT-emulsions of propofol.
|
A Multi-Center, Randomized, Double-Blind, Positive Controlled Study to Evaluate the Efficacy and Safety of Propofol(Propofol®-Lipuro) in Total Intravenous Anaesthesia
|
General Anaesthesia, Induction of Anaesthesia
|
* Drug: Propofol
|
Inclusion Criteria:~Female and male adult patients, and at least 18 and maximal 65 years of age;~ASA-classification I to II;~Undergoing an elective surgery, the anaesthesia is expected to last at least 1 hour and no more than 3 hours;~Will be under total intravenous anaesthesia;~Willing to give their signed informed consent.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to loss of eyelash reflex | | induction of anaesthesia |
| doses required for induction of anaesthesia until loss of eyelash reflex | | induction of anaesthesia |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patient data/history | | during anaesthesia |
| pre- and concomitant medication | | during anaesthesia |
| anaesthesia relating data | | during anaesthesia |
| recovery data | | during anaesthesia |
| drug safety data (e.g. haemodynamics and clinical outcome) | | during anaesthesia |
| adverse events | | during anaesthesia |
|
anaesthesia
|
Propofol, Hypnotics and Sedatives, Central Nervous System Depressants, Physiological Effects of Drugs, Anesthetics, Intravenous, Anesthetics, General, Anesthetics
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Propofol MCT/LCT | Drug: Propofol<br>* intravenous (total intravenous anaesthesia)~induction and maintenance<br>* Other names: Diprivan 1%;|
| Active Comparator: 2<br>Propofol LCT | Drug: Propofol<br>* intravenous (total intravenous anaesthesia)~induction and maintenance<br>* Other names: Diprivan 1%;|
|
Efficacy and Safety Study of Two Propofol Formulations
Study Overview
=================
Brief Summary
-----------------
The purpose of the study to compare Propofol-MCT/LCT with LCT in terms of their efficacy and safety during total intravenous anaesthesia
Detailed Description
-----------------
Propofol (chemical substance 2, 6-Diisopropylphenol) is a short-acting intravenous general anaesthetic which is used for induction and maintenance of a general anaesthesia, for long-term sedation of ventilated intensive care patients or for short-term sedation in diagnostic and surgical procedures. As an active substance propofol produces good and readily controlled anaesthesia with smooth and problem-free recovery both in adult patients and in children over 1 month of age. One potential advantage of this formulation is that the MCT/LCT-emulsion reduces pain on injection, a frequently reported adverse reaction with LCT-emulsions of propofol.
Official Title
-----------------
A Multi-Center, Randomized, Double-Blind, Positive Controlled Study to Evaluate the Efficacy and Safety of Propofol(Propofol®-Lipuro) in Total Intravenous Anaesthesia
Conditions
-----------------
General Anaesthesia, Induction of Anaesthesia
Intervention / Treatment
-----------------
* Drug: Propofol
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female and male adult patients, and at least 18 and maximal 65 years of age; ASA-classification I to II; Undergoing an elective surgery, the anaesthesia is expected to last at least 1 hour and no more than 3 hours; Will be under total intravenous anaesthesia; Willing to give their signed informed consent.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Propofol MCT/LCT | Drug: Propofol<br>* intravenous (total intravenous anaesthesia) induction and maintenance<br>* Other names: Diprivan 1%;|
| Active Comparator: 2<br>Propofol LCT | Drug: Propofol<br>* intravenous (total intravenous anaesthesia) induction and maintenance<br>* Other names: Diprivan 1%;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to loss of eyelash reflex | | induction of anaesthesia |
| doses required for induction of anaesthesia until loss of eyelash reflex | | induction of anaesthesia |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patient data/history | | during anaesthesia |
| pre- and concomitant medication | | during anaesthesia |
| anaesthesia relating data | | during anaesthesia |
| recovery data | | during anaesthesia |
| drug safety data (e.g. haemodynamics and clinical outcome) | | during anaesthesia |
| adverse events | | during anaesthesia |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
anaesthesia
|
NCT01023516
|
Efficacy and Safety of Twice Daily 60mg AZD9668 in COPD for 12 Weeks in Patients on Background Budesonide/Formoterol
|
The primary objective is to evaluate the efficacy of AZD9668 compared with placebo in symptomatic COPD patients by assessing the effects on lung function and symptoms of COPD
|
A 12-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Multinational, Phase IIb Study to Evaluate the Efficacy and Safety of 60mg AZD9668 Administered Orally Twice Daily to Subjects With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Budesonide/Formoterol
|
Chronic Obstructive Pulmonary Disease (COPD)
|
* Drug: AZD9668
* Drug: Placebo
|
Inclusion Criteria:~Diagnosis of COPD with symptoms over 1 year~FEV1/FVC < 70% and FEV1 >= 30 and < 80 % of predicted post-bronchodilator~Symptomatic COPD for a total of 7 days in the two weeks prior to randomisation~At least 1 COPD exacerbation from 4 weeks to 12 months before the screening visit~Exclusion Criteria:~Past history or current evidence of clinically significant heart disease~Current diagnosis of asthma~Patients who require long term oxygen therapy~Worsening of COPD requiring treatment with antibiotics, an increase in inhaled steroid dose and/or oral steroids within 4 weeks of study visit 1b
|
40 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Pre-bronchodilator FEV1 (L) | Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 |
| End-value Pre-bronchodilator FEV1 (L) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-bronchodilator FEV1 (L) - Baseline | Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 |
| Post-bronchodilator FEV1 (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Pre-bronchodilator FVC (L) - Baseline | Forced vital capacity (FVC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 |
| Pre-bronchodilator FVC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Post-bronchodilator FVC (L) - Baseline | Forced vital capacity (FVC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 |
| Post-bronchodilator FVC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Baseline Pre-bronchodilator FEV6 (L) | Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 |
| End-value Pre-bronchodilator FEV6 (L) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Baseline Post-bronchodilator FEV6 (L) | Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured post after bronchodilator (salbutamol) use in the clinic. | Day 1 |
| End-value Post-bronchodilator FEV6 (L) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Baseline Pre-bronchodilator FEF25-75% (L/Sec) | Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 |
| End-value Pre-bronchodilator FEF25-75% (L/Sec) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Baseline Post-bronchodilator FEF25-75% (L/Sec) | Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 |
| End-value Post-bronchodilator FEF25-75% (L/Sec) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Pre-bronchodilator IC (L) - Baseline | Inspiratory capacity (IC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 |
| Pre-bronchodilator IC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Post-bronchodilator IC (L) - Baseline | Inspiratory capacity (IC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 |
| Post-bronchodilator IC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| PEF - Baseline Measured by Patient at Home (L/Min) in the Morning | Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning. Baseline is the mean of last 10 days of data before start of treatment. | Baseline |
| PEF - End-value Measured by Patient at Home (L/Min) in the Morning | Peak expiratory flow (PEF) | Last 6 weeks on treatment |
| FEV1 - Baseline Measured by Patient at Home (L) in the Morning | Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning. Baseline is the mean of last 10 days of data before start of treatment. | Baseline |
| FEV1 - End-value Measured by Patient at Home (L) in the Morning | Forced Expiratory Volume in 1 second (L) | Last 6 weeks on treatment |
| EXACT - Baseline Total Score | EXAcerbations of Chronic pulmonary disease Tool, patient questionnaire as a measure of respiratory symptoms (reported as units on a 0 (best health status) to 100 (worst possible status) scale). Baseline is the mean of last 10 days of data before start of treatment. | Baseline |
| EXACT - End-value Total Score | EXAcerbations of Chronic pulmonary disease Tool, patient questionnaire as a measure of respiratory symptoms (reported as units on a 0 (best health status) to 100 (worst possible status) scale). | Last 6 weeks on treatment |
| BCSS - Baseline Total Score | Breathlessness, Cough and Sputum Scale, patient reported questionnaire as a measure of respiratory symptoms (reported on a 0 (best health status) to 12 (worst possible status) scale). Baseline is the mean of last 10 days of data before start of treatment. | Baseline |
| BCSS - End-value Total Score | Breathlessness, Cough and Sputum Scale, patient reported questionnaire as a measure of respiratory symptoms (reported on a 0 (best health status) to 12 (worst possible status) scale). | Last 6 weeks on treatment |
| Sputum Colour - Baseline | Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status). | Baseline |
| Sputum Colour - End Value | Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status). End of treatment week 12 | End of treatment week 12 |
| Use of Reliever Medication | Daily average of number of inhalations of reliever medication | Last 6 weeks on treatment |
| Incremental Shuttle Walk Test - Baseline | Endurance time (s) | Day 1 |
| Incremental Shuttle Walk Test - End Value | | Week 12 - visit 6 |
| Endurance Shuttle Walk Test - Baseline | Endurance time (s) | Day 1 |
| Endurance Shuttle Walk Test - End Value | Assessed at vist 6 -( last on treatment clinic visit) | Week 12 - visit 6 |
| St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline | St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease, as a measure of Quality of Life (reported on a scale from 0 (best health status) to 100(worst possible status)). | Day 1 |
| St George's Respiratory Questionnaire (COPD) - End-value Overall Score | St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease, as a measure of Quality of Life (reported on a scale from 0 (best health status) to 100(worst possible status)).Questionaire assessed on vist 6 -( last on treatment clinic visit) | Measured Day 1 and 12 weeks |
| Exacerbations - Clinic Defined | Number of patients having a clinic defined disease exacerbation. | Duration of the the treatment period - 12 weeks |
|
Chronic, obstructive, pulmonary, lung, respiratory disease, efficacy, placebo-controlled, COPD, FEV1, St Georges Respiratory Questionnaire
|
Lung Diseases, Lung Diseases, Obstructive, Pulmonary Disease, Chronic Obstructive, Respiratory Tract Diseases, Chronic Disease, Disease Attributes, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: AZD9668<br>* 2 x 30 mg oral tablets bd for 12 weeks<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* 2 x matched placebo to oral tablet bd for 12 weeks<br>|
|
Efficacy and Safety of Twice Daily 60mg AZD9668 in COPD for 12 Weeks in Patients on Background Budesonide/Formoterol
Study Overview
=================
Brief Summary
-----------------
The primary objective is to evaluate the efficacy of AZD9668 compared with placebo in symptomatic COPD patients by assessing the effects on lung function and symptoms of COPD
Official Title
-----------------
A 12-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Multinational, Phase IIb Study to Evaluate the Efficacy and Safety of 60mg AZD9668 Administered Orally Twice Daily to Subjects With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Budesonide/Formoterol
Conditions
-----------------
Chronic Obstructive Pulmonary Disease (COPD)
Intervention / Treatment
-----------------
* Drug: AZD9668
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of COPD with symptoms over 1 year FEV1/FVC < 70% and FEV1 >= 30 and < 80 % of predicted post-bronchodilator Symptomatic COPD for a total of 7 days in the two weeks prior to randomisation At least 1 COPD exacerbation from 4 weeks to 12 months before the screening visit Exclusion Criteria: Past history or current evidence of clinically significant heart disease Current diagnosis of asthma Patients who require long term oxygen therapy Worsening of COPD requiring treatment with antibiotics, an increase in inhaled steroid dose and/or oral steroids within 4 weeks of study visit 1b
Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: AZD9668<br>* 2 x 30 mg oral tablets bd for 12 weeks<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* 2 x matched placebo to oral tablet bd for 12 weeks<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Pre-bronchodilator FEV1 (L) | Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 |
| End-value Pre-bronchodilator FEV1 (L) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-bronchodilator FEV1 (L) - Baseline | Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 |
| Post-bronchodilator FEV1 (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Pre-bronchodilator FVC (L) - Baseline | Forced vital capacity (FVC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 |
| Pre-bronchodilator FVC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Post-bronchodilator FVC (L) - Baseline | Forced vital capacity (FVC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 |
| Post-bronchodilator FVC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Baseline Pre-bronchodilator FEV6 (L) | Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 |
| End-value Pre-bronchodilator FEV6 (L) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Baseline Post-bronchodilator FEV6 (L) | Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured post after bronchodilator (salbutamol) use in the clinic. | Day 1 |
| End-value Post-bronchodilator FEV6 (L) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Baseline Pre-bronchodilator FEF25-75% (L/Sec) | Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 |
| End-value Pre-bronchodilator FEF25-75% (L/Sec) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Baseline Post-bronchodilator FEF25-75% (L/Sec) | Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 |
| End-value Post-bronchodilator FEF25-75% (L/Sec) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Pre-bronchodilator IC (L) - Baseline | Inspiratory capacity (IC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 |
| Pre-bronchodilator IC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| Post-bronchodilator IC (L) - Baseline | Inspiratory capacity (IC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 |
| Post-bronchodilator IC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 |
| PEF - Baseline Measured by Patient at Home (L/Min) in the Morning | Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning. Baseline is the mean of last 10 days of data before start of treatment. | Baseline |
| PEF - End-value Measured by Patient at Home (L/Min) in the Morning | Peak expiratory flow (PEF) | Last 6 weeks on treatment |
| FEV1 - Baseline Measured by Patient at Home (L) in the Morning | Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning. Baseline is the mean of last 10 days of data before start of treatment. | Baseline |
| FEV1 - End-value Measured by Patient at Home (L) in the Morning | Forced Expiratory Volume in 1 second (L) | Last 6 weeks on treatment |
| EXACT - Baseline Total Score | EXAcerbations of Chronic pulmonary disease Tool, patient questionnaire as a measure of respiratory symptoms (reported as units on a 0 (best health status) to 100 (worst possible status) scale). Baseline is the mean of last 10 days of data before start of treatment. | Baseline |
| EXACT - End-value Total Score | EXAcerbations of Chronic pulmonary disease Tool, patient questionnaire as a measure of respiratory symptoms (reported as units on a 0 (best health status) to 100 (worst possible status) scale). | Last 6 weeks on treatment |
| BCSS - Baseline Total Score | Breathlessness, Cough and Sputum Scale, patient reported questionnaire as a measure of respiratory symptoms (reported on a 0 (best health status) to 12 (worst possible status) scale). Baseline is the mean of last 10 days of data before start of treatment. | Baseline |
| BCSS - End-value Total Score | Breathlessness, Cough and Sputum Scale, patient reported questionnaire as a measure of respiratory symptoms (reported on a 0 (best health status) to 12 (worst possible status) scale). | Last 6 weeks on treatment |
| Sputum Colour - Baseline | Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status). | Baseline |
| Sputum Colour - End Value | Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status). End of treatment week 12 | End of treatment week 12 |
| Use of Reliever Medication | Daily average of number of inhalations of reliever medication | Last 6 weeks on treatment |
| Incremental Shuttle Walk Test - Baseline | Endurance time (s) | Day 1 |
| Incremental Shuttle Walk Test - End Value | | Week 12 - visit 6 |
| Endurance Shuttle Walk Test - Baseline | Endurance time (s) | Day 1 |
| Endurance Shuttle Walk Test - End Value | Assessed at vist 6 -( last on treatment clinic visit) | Week 12 - visit 6 |
| St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline | St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease, as a measure of Quality of Life (reported on a scale from 0 (best health status) to 100(worst possible status)). | Day 1 |
| St George's Respiratory Questionnaire (COPD) - End-value Overall Score | St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease, as a measure of Quality of Life (reported on a scale from 0 (best health status) to 100(worst possible status)).Questionaire assessed on vist 6 -( last on treatment clinic visit) | Measured Day 1 and 12 weeks |
| Exacerbations - Clinic Defined | Number of patients having a clinic defined disease exacerbation. | Duration of the the treatment period - 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic, obstructive, pulmonary, lung, respiratory disease, efficacy, placebo-controlled, COPD, FEV1, St Georges Respiratory Questionnaire
|
|
NCT04119869
|
Smart Phone App Intervention In Young Adults With Cancer
|
This research study aims to explore the feasibility and acceptability of a smartphone application intervention, called iaya, among young adults with cancer.
|
The iaya app was developed by clinicians from the Young Adult Program at the Dana-Farber Cancer Institute. The iaya app is a smartphone application intervention that -through a variety of approaches, such as exercises aimed at identifying and changing thoughts and behaviors, imagery, and relaxation- seeks to enhance coping with the emotional impact of cancer.~The investigators are conducting this study to see if the iaya app, specifically developed for young adults with cancer, is practical, to determine patient satisfaction with the iaya app, and to test study procedures.
|
Feasibility and Acceptability of a Smart Phone Application Intervention to Enhance Coping for Young Adults With Cancer
|
Cancer, Young Adults, Behavioral Intervention, Smartphone Application
|
* Other: iaya
|
Inclusion Criteria:~Patients aged 18-39 years~Able to speak/read English~Have a smart phone~Receiving cancer treatment~Active cancer care from an oncologist at Dana-Farber Cancer Institute~Exclusion Criteria:~Neurological/cognitive condition interfering with the ability to understand and adhere to study procedures~Adults unable to consent~Individuals who are not yet adults (infants, children, teenagers)~Pregnant women~Prisoners
|
18 Years
|
39 Years
|
All
|
No
|
Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who log in at least 10 times and open at least 3 coping skills exercises | Feasibility of iaya will be determined by calculating the percent of participants assigned to the iaya app who log in at least 10 times. Percent of participants assigned to the iaya app will open at least 3 coping skills exercises will also be considered as a component of feasibility. | 12 weeks |
| Mean score on app usability questionnaire | Acceptability will be assessed with the 6-item app usability questionnaire rated on a Likert scale (0=strong disagree to 5=strongly agree). Items will prompt participants to rate the extend to which they would use this app frequently, found the app to be easy to use, well organized, learn how to use the app quickly, felt confident using the app, and if they found the app interactive. Scores can range from 0-30. Higher scores indicate higher perception of usability. | 12 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in coping scores on the Cancer Behavior Inventory Brief Form | We will pilot the 12-item Cancer Behavior Inventory Brief Form (CBI-B) for future efficacy studies. The CBI-B measures self-efficacy for coping with cancer. Items are scored between 1 (not at all confident) to 9 (totally confident). Higher scores indicate a higher level of self-efficacy for coping with cancer.~among young adults with cancer who had access to the iaya app for future efficacy studies. | 12 weeks |
| Change in self-efficacy scores on the PROMIS Self-Efficacy for Managing Emotions Scale | We will pilot the 8-item PROMIS Self-Efficacy for Managing Emotions (PROMIS SEMEM) for future efficacy studies. The PROMIS SEMEM will be used to measure confidence to manage or control symptoms of anxiety, depression, helplessness, discouragement, frustration, disappointment, and anger. Items are scored on a scale from 1 (not at all confident) to 5 (very confident). Higher scores indicate a higher level of self-efficacy for managing emotions. | 12 weeks |
| Change in emotional support on the PROMIS Emotional Support Scale | We will pilot the 12-item PROMIS Emotional Support (PROMIS ES) for future efficacy studies. The PROMIS ES measures perceived feelings of being cared for and valued as a person. Items are scores on a scale from 1 (never) to 5 (always). Higher scores indicate higher levels of perceived emotional support. | 12 weeks |
| Change in quality of life on the Functional Assessment of Cancer Therapy-General Scale | We will pilot the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) for future efficacy studies. The FACT-G consists of four sub scales: physical, emotional, social/family, and functional well-being. Items are scores between 0 (not at all) and 4 (very much). Higher scores indicate a higher level of quality of life. | 12 weeks |
|
Cancer, Young Adults, Behavioral Intervention, Smartphone Application
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iaya Smart Phone Application<br>Pre-study evaluation~Access to the smartphone intervention over the course of 12 weeks~Post-study evaluation and interview | Other: iaya<br>* The iaya app is a smartphone application intervention that -through a variety of approaches, such as exercises aimed at identifying and changing thoughts and behaviors, imagery, and relaxation- seeks to enhance coping with the emotional impact of cancer.<br>|
|
Smart Phone App Intervention In Young Adults With Cancer
Study Overview
=================
Brief Summary
-----------------
This research study aims to explore the feasibility and acceptability of a smartphone application intervention, called iaya, among young adults with cancer.
Detailed Description
-----------------
The iaya app was developed by clinicians from the Young Adult Program at the Dana-Farber Cancer Institute. The iaya app is a smartphone application intervention that -through a variety of approaches, such as exercises aimed at identifying and changing thoughts and behaviors, imagery, and relaxation- seeks to enhance coping with the emotional impact of cancer. The investigators are conducting this study to see if the iaya app, specifically developed for young adults with cancer, is practical, to determine patient satisfaction with the iaya app, and to test study procedures.
Official Title
-----------------
Feasibility and Acceptability of a Smart Phone Application Intervention to Enhance Coping for Young Adults With Cancer
Conditions
-----------------
Cancer, Young Adults, Behavioral Intervention, Smartphone Application
Intervention / Treatment
-----------------
* Other: iaya
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged 18-39 years Able to speak/read English Have a smart phone Receiving cancer treatment Active cancer care from an oncologist at Dana-Farber Cancer Institute Exclusion Criteria: Neurological/cognitive condition interfering with the ability to understand and adhere to study procedures Adults unable to consent Individuals who are not yet adults (infants, children, teenagers) Pregnant women Prisoners
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 39 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iaya Smart Phone Application<br>Pre-study evaluation Access to the smartphone intervention over the course of 12 weeks Post-study evaluation and interview | Other: iaya<br>* The iaya app is a smartphone application intervention that -through a variety of approaches, such as exercises aimed at identifying and changing thoughts and behaviors, imagery, and relaxation- seeks to enhance coping with the emotional impact of cancer.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who log in at least 10 times and open at least 3 coping skills exercises | Feasibility of iaya will be determined by calculating the percent of participants assigned to the iaya app who log in at least 10 times. Percent of participants assigned to the iaya app will open at least 3 coping skills exercises will also be considered as a component of feasibility. | 12 weeks |
| Mean score on app usability questionnaire | Acceptability will be assessed with the 6-item app usability questionnaire rated on a Likert scale (0=strong disagree to 5=strongly agree). Items will prompt participants to rate the extend to which they would use this app frequently, found the app to be easy to use, well organized, learn how to use the app quickly, felt confident using the app, and if they found the app interactive. Scores can range from 0-30. Higher scores indicate higher perception of usability. | 12 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in coping scores on the Cancer Behavior Inventory Brief Form | We will pilot the 12-item Cancer Behavior Inventory Brief Form (CBI-B) for future efficacy studies. The CBI-B measures self-efficacy for coping with cancer. Items are scored between 1 (not at all confident) to 9 (totally confident). Higher scores indicate a higher level of self-efficacy for coping with cancer. among young adults with cancer who had access to the iaya app for future efficacy studies. | 12 weeks |
| Change in self-efficacy scores on the PROMIS Self-Efficacy for Managing Emotions Scale | We will pilot the 8-item PROMIS Self-Efficacy for Managing Emotions (PROMIS SEMEM) for future efficacy studies. The PROMIS SEMEM will be used to measure confidence to manage or control symptoms of anxiety, depression, helplessness, discouragement, frustration, disappointment, and anger. Items are scored on a scale from 1 (not at all confident) to 5 (very confident). Higher scores indicate a higher level of self-efficacy for managing emotions. | 12 weeks |
| Change in emotional support on the PROMIS Emotional Support Scale | We will pilot the 12-item PROMIS Emotional Support (PROMIS ES) for future efficacy studies. The PROMIS ES measures perceived feelings of being cared for and valued as a person. Items are scores on a scale from 1 (never) to 5 (always). Higher scores indicate higher levels of perceived emotional support. | 12 weeks |
| Change in quality of life on the Functional Assessment of Cancer Therapy-General Scale | We will pilot the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) for future efficacy studies. The FACT-G consists of four sub scales: physical, emotional, social/family, and functional well-being. Items are scores between 0 (not at all) and 4 (very much). Higher scores indicate a higher level of quality of life. | 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cancer, Young Adults, Behavioral Intervention, Smartphone Application
|
|
NCT03781895
|
Effect of Vitamin D3 on Lung Function and Exercise Tolerance in COPD Patients
|
Background: Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality throughout the world which is a preventable as well as treatable disease. It has some important extra pulmonary effects which may contribute to the magnitude of the severity of this disease. Standard therapeutic treatment alone does not optimize its remedy. Vitamin D3 has been found to improve the physical efficiency of patients with various morbid disorders, including respiratory ailments. Hypothesis:Vitamin D3 administration in stable patients with moderate COPD improves lung function variables along with exercise tolerance.~Objectives: To evaluate the effects of Vitamin D3 on lung functions and exercise tolerance in patients with stable moderate COPD. Methods: For this, a prospective interventional randomized double blinded study will be carried out on 46 vitamin D3 deficient (serum 25 dihidroxycholecalceferol less than 30 ng/ml), male, stable (diagnosed patient, who has not experienced any acute exacerbation , hospitalizations , urgent care visits, or changes in routine medication within 4 weeks prior to study), moderate (post bronchodilator FEV1/FVC<0.70 of predicted value and FEV1=50 to 79% of predicted value) COPD patients (age ≥40 years), who will be selected from the Out Patient Department (OPD) of the National Institute of Diseases of Chest and Hospital (NIDCH) and will be grouped as A (control) and B (study) groups, respectively. All the patients will be again designated as A0, A90 (without D3) and B0, B90 (with D3) for before and after 90 days of follow up. All the participants will be matched in terms of duration of COPD, history of smoking, occupation and socioeconomic status. Along with the standard pharmacological treatment of COPD, the patients of the 'Study group' will be prescribed for 80000 IU of oral vitamin D3 pre week for consecutive 3 months. Along with this, all patients both the groups will be advised to continue ad lib (according to their own choice) diet. At the very 1st day of the study, the lung functions will be assessed by measuring Forced vital capacity (FVC), Forced expiratory volume in one second (FEV1), Forced expiratory ratio (FEV1/FVC%), Peak expiratory flow rate (PEFR) and Forced mid expiratory flow of FVC(FEF25-75%), with a portable digital spirometer. In addition, exercise tolerance will be assessed by change in 6 Minute Walk Distance (6MWD) in 6 Minute Walk Test (6MWT). Changes in peripheral capillary oxygen saturation (SpO2) by Pulse Oximeter and degree of dyspnoea by Modified Borg Scale (MBS) will also be measured both before and after 6MWT to evaluate their change in both the groups. All these variables will be measured again among same 46 patient after 90 days standard pharmacological treatment of COPD with D3 intervention (B group) and also without D3 intervention (A group). For statistical analysis, Chi-square test, independent sample 't' test between two groups, paired Student's 't' test within two specific measurements of different durations of each group ,will be done. In the interpretation of results, ≤0.05 level of probability (p) will be accepted as significant.
|
Introduction:~Chronic Obstructive Pulmonary Disease (COPD) is one of the major causes of chronic morbidity and mortality throughout the world . Many people suffer from the disease for years and die too early from its complications. COPD is the fourth leading cause of death in adults of United States and also projected to be the third by 2020 .Though it is a preventable and treatable disease, once developed the disease along with its comorbidities cannot be cured. But its progression and morbidity can be reduced.~The airflow obstruction in this disease is generally persistent as well as progressive .It has two clinical phases (stable phase and exacerbation phase), both of which are associated with inflammation .Independent risk factors for COPD are male gender, advanced age, low socioeconomic status, occupational exposure and cigarette smoking (both active and passive) ,reactivity of airways, occupational factors and air pollution .~Vitamin D is a steroid important in bone mineralization and calcium homeostasis. The prevalence of vitamin D deficiency has been increasing in the general population in recent decades. The majority of circulating 25-hydroxyvitamin D [25(OH)D] is derived from sun exposure with a limited dietary contribution. The increased prevalence of vitamin D deficiency is attributed to sun avoidance, indoor lifestyle, use of sunscreen, and decreased intake of vitamin D-containing foods .Because vitamin D is sequestered in adipose tissue, the increasing prevalence of obesity also increases the prevalence of vitamin D deficiency .~Recently, research has found that vitamin D may play a role in multiple chronic diseases such as cancer, autoimmune diseases, infections, and cardiovascular disorders . Vitamin D may also have a role in several diseases involving the respiratory system. Recently some researchers reported that a significant proportion of young COPD patients may have insufficient (20 to 29 ng/ml) serum 25-OHD . Moreover, higher serum vitamin D concentrations, assessed by [25(OH)D], have been associated with better lung function as measured by FEV1 in a large cross-sectional study of the U.S. population . Although the precise connection between vitamin D status and lung function is not clear at this point, it is postulated that vitamin D may improve lung function through its action on regulating inflammation ,inducing antimicrobial peptides , and/or its action on muscles .~It has also been suggested that, patients with COPD have a high prevalence of vitamin D deficiency, ranging from approximately 30% in mild COPD to over 75% in severe COPD. Particularly for COPD, vitamin D deficiency may enhance chronic airway and systemic inflammation, reduce bacterial clearance, and increase the risk for infectious exacerbations at the same time .~To provide a quick, acceptable as well as repeatable and reproducible lung function data spirometry is a safe and practical procedure .The ventilatory functions of the lung such as, forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1), FEV1/FVC ratio (FEV1/FVC %), forced mid expiratory flow rate between 25% and 75% of FVC (FEF25-75%) and peak expiratory flow rate (PEFR), can be assessed by spirometry. The indices derived from this forced exhaled maneuver have become the most accurate and reliable way of supporting a diagnosis of COPD . This test should be undertaken in all patients who may have COPD. It is needed to make a confident diagnosis as well as to exclude other diagnoses that may present with similar symptoms. Although spirometry does not fully capture the impact of COPD on a patient's health, it remains the gold standard for diagnosing the disease and monitoring its progression. It is the best standardized most reproducible and most objective measurement of airflow limitation available .~In addition, oxygen saturation is an indicator of the percentage of hemoglobin saturated with oxygen at the time of the measurement. Peripheral capillary oxygen saturation values obtained from pulse oximetry (SpO2) is one part of a complete assessment of the patient's oxygenation status. Normal oxygen saturation values are 97% to 99% in the healthy individual and of 95% is clinically accepted in a patient with a normal hemoglobin level . This value may vary with the amount of oxygen utilization by the tissues. For example, in some patients, there is a difference in SpO2 values at rest compared with those during activity, such as ambulation or positioning. However it does not reflect the patient's ability to ventilate .~Moreover, dyspnea is one of the most significant symptoms occurring during the progression of COPD and results from pulmonary hyperinflation, weakness of inspiratory muscles, increased ventilation, voluntary hyperventilation, increased respiratory work load and impaired function of the inspiratory muscles . The evaluation of dyspnea is very important in any chronic respiratory ailment. The effort dyspnea determined at the end of exercise is accepted as the best indicator of dyspnea .There are several scales are available to evaluate dyspnea. Though the interpretation of dyspnea scales depends solely on the statements of the patients, but Modified Borg Scale (MBS) is known to be simple and partially objective, have usually been used to evaluate effort dyspnea in clinical practice .~Respiratory disease often presents with limited activity level and exercise capacity and reduced exercise tolerance is a hallmark of patients with COPD . In 1963, Balke developed a simple test to evaluate the functional capacity by measuring the distance walked during a period of time. Walk test are typically administered as a means of evaluating functional status, monitoring treatment effectiveness and establishing prognosis. The 6 minutes walk test (6 MWT) is a practical simple test that requires a 30 meter hallway but no exercise equipment or advance training for the observer. The test measures the distance that a person can quickly walk on a flat, hard surface in a period of 6 minutes. The self paced 6 MWT assesses the submaximal level of functional capacity. However, because most activities of daily living are performed at submaximal levels of exertion, the 6 minutes walk distance (6 MWD) may better reflect the functional exercise level for daily physical activities.~Rationale:~Standard therapeutic treatment schedule has a limited role in improving the physical capacity in COPD patients .Various supplementations and extra-therapeutic measures have been tried to improve the functional capacity of the COPD patients . Vitamin D3 supplementation is one of them. The principal goals of adding vitamin D3 in the treatment schedule of these patients are to reduce symptoms and exacerbations, to improve quality of life and to increase physical and emotional participation in everyday activities which may not be adequately addressed by standard pharmacological regime alone for COPD .Recently, a number of studies have shown an association between vitamin D deficiency and severity of COPD . In addition in a prospective study, FEV1 was measured in patients with severe and very severe COPD both before and after vitamin D3 supplementation and significant improvement was found .On the other hand, one recent study reported no significant improvement in FVC, FEV1 and FEV1/FVC% in Vitamin D3 insufficient COPD patients after vitamin D3 administration as compared to that of the control group .~However the volume of information regarding the effect of vitamin D3 administration in COPD patients is not enough for reaching any final conclusion. Moreover, with the best of our knowledge no study have been conducted to observe the effects of this fat soluble vitamin on the spirometric lung function status, oxygen saturation and exercise tolerance in vitamin D3 insufficient, stable patients with moderate COPD.~Therefore, on the basis of this background the present study has been designed to evaluate the effects of Vitamin D3 on the spirometric lung function status, peripheral capillary oxygen saturation and exercise tolerance in D3 insuffucient, male patients with stable moderate COPD. This study will draw attention of the physicians about the beneficial effects of the vitamin D3 on both pulmonary and extrapulmonary complications in COPD patients.~Research Question:~Does vitamin D3 has any effect on lung function and exercise tolerance in stable COPD patients?~Hypothesis:~Vitamin D3 administration in stable patients with moderate COPD improves lung function variables along with exercise tolerance.~Objectives:~General Objective To evaluate the effects of vitamin D3 administration on lung functions and exercise tolerance in vitamin D3 insufficient male patients with stable moderate COPD.~Specific Objectives~To measure the FVC, FEV1, FEV1/FVC%, PEFR and FEF25-75% of vitamin D3 insufficient male patients with stable moderate COPD, in order to assess their lung function status.~To measure the SpO2 at rest, in order to assess the basal oxygenation status in this group of patients.~To determine level of dyspnea at rest, in order to assess the basal breathlessness level in the same group of patients~To measure the 6MWD of all the patients, in order to assess their functional exercise capacity.~To measure both the SpO2 and level of dyspnea again after 6MWT, for the assessment of their exercise tolerance.~To measure all these variables after 90 days standard pharmacological treatment with vitamin D3 and also without vitamin D3 in stable COPD patients.~To compare the results of baseline and endline.~Methodology:~TYPE OF STUDY : Prospective interventional randomized double blinded study PLACE OF STUDY : Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka STUDY PERIOD : March 2017 to February 2018 STUDY POPULATION : Stable, moderate COPD patients with vitamin D3 insufficiency.~SAMPLE SIZE : 46 SAMPLING : Simple random sampling . According to the selection criteria total 46 COPD patients suitable for the aims and objectives of the study, will be enrolled. 46 patients of COPD will be selected by clinician in OPD.~GROUPING OF THE SUBJECTS :~Group A (Control group) : 23 D3 insufficient COPD patients without D3 administration A0 : On day 0 A90 : On day 90 Group B (Study group) : 43 (forty three) D3 insufficient COPD patients with D3 administration B0 : On day 0 B90 : On day 90~Sample size calculation:~Using the following statistical formula n = (Zα+Zβ) 2 X (σ12+σ22) (μ1-μ2)2~Here, Using the following statistical formula n = [(Zα+Zβ)2 X (σ12+σ22)] / (μ1-μ2)2 Mean of control, μ1 = 47.1 Mean of study group, μ2 = 67.4 SD of control, σ1 = 26.9 SD of study group, σ2 = 27.5 (Martineau et al. 2015) Type I Error, Zα = 1.96 Type II Error, Zβ = 1.64 (Kirkwood and Sterne 2003) (Kirkwood and Sterne 2003)~Therefore, n = [(Zα+Zβ)2 X (σ12+σ22)] / (μ1-μ2)2~[(1.96+1.64)2 X (26.92 +27.52) / (47.1-67.4)2~[12.96 X (756.25+723.61)] / (20.3) 2 = 19178.98 / 412.09 = 46.54 = 47~Subject Selection:~After selection of subject the researcher will sit for an interview with the subject. The researcher will at first introduce himself mentioning his institutional affiliation, conflict of interest and will supply address, contact telephone number and information about sponsorship. After that the subject will be thoroughly informed about the objectives and outcome of the study. Brief explanation of the procedure will be given to them. The subject will also be assured if any problem arises during the test; it will be taken care of. The result of the test will be sent to him free of charge and if any abnormality is detected, then appropriate management will be given to him, if possible or will be referred to specific treatment facility as appropriate. He will be encouraged for voluntary participation in a cordial and friendly attitude and will be allowed freedom to withdraw from the study whenever he likes even after participation. They will be informed about the method of confidentiality of their identification. Their identity will be recorded only in questionnaire which will be kept in safe custody with the researcher. It will not enter in the computer and will not go in any publication. No personal identification will be used in data analysis, report writing or publication. They will also be assured that interview time will minimum for maintaining their comfort, some questions will be asked about the personal, family and medical history without any private enquiry. The conflict of interest will be told to him if there is any. After he has understood these entire procedure, if he agrees to participate, then a willingly given informed written consent will be taken from him.~There is no possibility of any physical, social or mental risk of the respondent. A pretested questionnaire will be filled up by the research assistant.~All gathered information will be kept secret and only will be used for medical research and analysis.~SITE OF SAMPLE COLLECTION:~All the patients will be collected from the Out Patient Department (OPD) of National Institute of Diseases of Chest and Hospital~STUDY PROCEDURE:~On the first day of enrollment, the objectives, nature, purpose and potential risk of all the procedures used for the study will be explained in detail to each subject, with a cordial attitude giving emphasis on the benefits he might obtain from this study. He will be encouraged for voluntary participation and will be allowed to withdraw himself from the study even after participation, whenever he felt uneasy. If he agreed to be enrolled in the study, an informed written consent will be taken in a prescribed form . Detailed family history, medical history and thorough physical examination of each patient will be done and all the information will be recorded in a standard data sheet . Then all the patients will be requested to attend the Department of Physiology at 9 am (about 1 and 1/2 hours after his breakfast) on the day of biochemical and spirometric examination.~On the examination day, 5 ml of venous blood will be collected and taken to the Hematology laboratory as soon as possible for the estimation of serum 25-hydroxycholecalceferol, serum glucose 2 hours after breakfast and serum creatinine. After that his height and weight will be measured and the spirometric lung function test will be done by using a portable spirometer. After getting all the biochemical and spirometric reports the final selection will be done, according to the inclusion and exclusion criteria.~Subsequently, all the eligible patients will be randomly assigned to either 'Control' or 'Study' groups and will be thoroughly informed about the objectives and detailed study procedure, once again. Then the patients will be examined for the baseline value of all the study variables in Day 1.~Again after 90 days the study variables will be collected from same 86 patients.~Vitamin D3~Ingredient~Cholecalciferol (40,000IU)~Microcrystalline Cellulose (58.1 gm)~Butylated Hydroxy Toluene ( 0.2mg)~Magnesium Stearate (3mg)~Gelatin Capsule Shell (1mg)~Dose : 80,000 IU/wk~Route : Oral~Placebo : Courtesy of Beximco Pharmaceuticals Limited~Bangladesh Ingredient : • Microcrystalline Cellulose (303.8gm)~Butylated Hydroxy Toluene (0.2mg)~Magnesium Stearate (3mg)~Gelatin Capsule Shell (1mg)~STUDY VARIABLES:~Spirometric variables~• FVC (L) : Forced Vital Capacity~• FEV1 (L) : Forced Expiratory Volume in 1st second~FEV1/FVC Ratio (%) : Forced Expiratory Ratio~PEFR (L/min) : Peak Expiratory Flow Rate~FEF 25-75 (L/S) : Forced Expiratory Flow in the middle of FVC~Oxygenation variables~• Resting SpO2 (%) : Resting Peripheral Capillary Oxygen saturation~Exercise tolerance variables • 6MWD (meter) : Six Minute Walk Distance • Level of Dyspnea : Modified Borg Scale~Hematological variables • 25(OH)D (ng/ml) : 25-hydroxycholecalceferol • PTH (pmol/l) : Parathyroid hormone • Ca2+ (mg/ml) : Ionic calcium • PO43- (mg/ml)~Ionic phosphate~AP (U/L) : Alkaline Phosphatase~Subsequently a standard therapeutic treatment will be prescribed to all the selected stable moderate COPD patients. In addition, the patients of the 'Study group' will be prescribed for 80000 IU of oral vitamin D3 per week for consecutive 90 days . Along with this, all the patients of both the groups will be advised to continue ad lib (according to their own choice) diet.~Proper education will be given about drug , method of taking medication and medication plan.Afterwards,a good rapport will be built up to take time to time follow up over telephone and visiting patient's place .Schedule appointment ,hotline and follow up will be maintained properly. They will be requested to attend the Department of Physiology again on the 90th day, to have the assessment of all the above-mentioned study variables Any patient, who failed to follow the study procedure exactly during study period, will be dropped and a new one will be included to fulfill the desired total sample number.Thats why extended sample should be taken to fulfill the total sample number.
|
Effect of Vitamin D3 on Lung Function and Exercise Tolerance in D3 Deficient COPD Patients
|
Stable COPD Patients
|
* Drug: Cholecalciferol
|
Inclusion Criteria:~Socioeconomic status: Middle class~Smoker~Stable patients of COPD with >1year duration~Vitamin D3 deficient :~Serum 25-hydroxycholecalciferol, [25(OH)D] level <30ng/ml (Vitamin D Council 2017)~Exclusion Criteria:~With acute exacerbation of any pulmonary diseases, as,~with acute exacerbation of any cardiac disease, like -~Uncontrolled systemic hypertension~Chronic liver disease~Malignancy~Use of drugs known to affect vitamin D metabolism within 1 month prior to With biochemical evidence of -~uncontrolled diabetes mellitus and~renal insufficiency~All the criteria mentioned above were scrutinized by taking history and clinical examination, except vitamin D3 deficiency, uncontrolled diabetes mellitus and renal insufficiency, which were diagnosed biochemically.
|
40 Years
|
70 Years
|
Male
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two groups of Vitamin D3 deficient stable COPD patients were taken, Group A was given placebo along with standard therapeutic treatment and Group B was given Vitamin D3 along with standard therapeutic treatment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung function (Spirometric variables) Forced Vital Capacity(FVC) will be changed | Forced Vital Capacity It is the volume of air that can be expired as forcefully and rapidly as possible after maximal inspiration. In adult male it is about 4.6 liters. The FVC is commonly reduced in obstructive processes such as COPD.Increment of Forced Vital Capacity means improvement in outcome. | After 90 days FVC will be measured again |
| Lung function [ Lung function (Spirometric variables): Forced Expiratory Volume in 1st second(FEV1) will be changed | Forced Expiratory Volume in 1st second When a person inspires maximally and exhales forcefully, then the volume, which is exhaled in 1st second is known as 'Forced Expiratory volume in 1st second'. It is normally 80% of forced vital capacity .~Significance- This measurement is much more sensitive index of severity of the obstructive disease .In COPD ,FEV1 is reduced ,Increment of FEV1 indicates improvent in outcome | After 90 days FEV1 will be measured again |
| Lung function (Spirometric variables) Forced Expiratory Ratio [FEV1/FVC Ratio (%)] will be changed | Forced Expiratory Ratio It is the ratio of FEV1 to FVC expressed in percentage. FEV1/FVC ratio = FEV1/FVC×100. It is about 70% or higher.~Forced Expiratory Ratio is less than 70% in COPD patients.Increment of Forced Expiratory Ratio indicates improvement in outcome | After 90 days FEV1/FVC Ratio will be measured again |
| Lung function (Spirometric variables) Peak Expiratory Flow Rate [PEFR (L/min)] will be changed | Peak Expiratory Flow Rate It is the maximum expiratory rate, beyond which the flow cannot be increased even with greatly increased additional force.~In adult it is about 400-700 Liter/second. | After 90 days PEFR will be measured again |
| Lung function (Spirometric variables) Forced Expiratory Flow in the middle of FVC [FEF 25-75 (Liter/Second) ] will be changed | Forced Expiratory Flow in the middle of FVC Forced expiratory flow during the middle half of the FVC. Formerly it was called the maximal mid-expiratory flow (MMEF), expressed in liters/second Normal range in male : 1.5-4.5 Liter/second.Increment of Forced Expiratory Flow in the middle of FVC means improvement in outcome. | After 90 days FEF 25-75 will be measured again |
| Lung function (Spirometric variables) Maximum expiratory Flow rate at 25%of the FVC (MEF 75) will be changed | Maximum expiratory Flow rate at 25%of the FVC (MEF 75) Maximum expiratory flow rate when 25% of the FVC remains in the lung to be exhaled and is equivalent to the FEF75 where 75% of the FVC has been exhaled. Expressed in liters/second.~This is reduced in COPD. Increment in maximum expiratory flow at 25%of the FVC means improvement in outcome | After 90 days MEF 75 will be measured again |
| Lung function (Spirometric variables) Maximum expiratory Flow at 50%of the FVC(MEF50) will be changed | Maximum expiratory Flow at 50%of the FVC(MEF50) Maximum expiratory flow rate when 50 % of the FVC remains in the lung to be exhaled and is equivalent to the FEF50 where 50% of the FVC has been exhaled. Expressed in liters/second. This is reduced in COPD.~Increment in maximum expiratory flow at 50%of the FVC means improvement in outcome. | After 90 days MEF 50 will be measured again |
| Lung function (Spirometric variables) Maximum expiratory Flow at 75%of the FVC (MEF25)]will be changed | Maximum expiratory Flow at 75%of the FVC (MEF25) Maximum expiratory flow rate when 75% of the FVC remains in the lung to be exhaled and is equivalent to the FEF25 where 25% of the FVC has been exhaled. Expressed in liters/second.This is reduced in COPD.Increment in maximum expiratory flow at 75%of the FVC means improvement in outcome | After 90 days MEF25 will be measured again |
| Exercise Tolerance [Oxygenation variables] Peripheral Capillary Oxygen saturation[SpO2 (%) ] will be changed | Oxygenation variables Peripheral Capillary Oxygen saturation between 96% to 99% is normal.Peripheral Capillary Oxygen saturation between 96% to 99% means improved outcome | After 90 days SpO2 will be measured |
| Exercise Tolerance Exercise tolerance variables •Six Minute Walk Distance[6MWD (meter) ]will be changed | Exercise tolerance variables • Six Minute Walk Distance [6MWD (meter) ] minimum 350m in 6minute at a time(without taking any rest) is standard.The more the distance,the more the better outcome. | After 90 days 6MWD will be measured |
| Exercise Tolerance variables • Level of Dyspnea : Modified Borg Scale will be changed | Level of Dyspnea : Modified Borg Scale If the dyspnea score decreases,it means better outcome If the dyspnea score increases,it means outcome is worse | After 90 days level of Dyspnea will be measured |
| Exercise Tolerance variables Level of fatigue: Modified Borg Scale will be changed | Level of fatigue: Modified Borg Scale If the fatigue score decreases,it means better outcome, If the fatigue score increases,it means outcome is worse | After 90 days level of fatigue will be measured |
|
COPD, VitaminD3, 6 Minute Walk Distance, Modified BORG scale
|
Cholecalciferol, Vitamin D, Calcium-Regulating Hormones and Agents, Physiological Effects of Drugs, Vitamins, Micronutrients, Bone Density Conservation Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A0<br>A0- On day 0,before intervention placebo,~Microcrystalline Cellulose (303.8gm)~Butylated Hydroxy Toluene (0.2mg)~Magnesium Stearate (3mg)~Gelatin Capsule Shell (1mg)~weekly,orally,for 90days | Drug: Cholecalciferol<br>* • Cholecalciferol (40,000IU),~,Microcrystalline Cellulose (58.1 gm), Butylated Hydroxy Toluene ( 0.2mg),Magnesium Stearate (3mg),Gelatin Capsule Shell (1mg)<br>* Other names: Magnesium Stearate (3mg);|
| Placebo Comparator: A90<br>A90- On day 90,after intervention placebo,~Microcrystalline Cellulose (303.8gm)~Butylated Hydroxy Toluene (0.2mg)~Magnesium Stearate (3mg)~Gelatin Capsule Shell (1mg)~weekly,orally,for 90days | Drug: Cholecalciferol<br>* • Cholecalciferol (40,000IU),~,Microcrystalline Cellulose (58.1 gm), Butylated Hydroxy Toluene ( 0.2mg),Magnesium Stearate (3mg),Gelatin Capsule Shell (1mg)<br>* Other names: Magnesium Stearate (3mg);|
| Active Comparator: B0<br>B0- On day 0,before intervention cholecalciferol,~Cholecalciferol (40,000IU)~Microcrystalline Cellulose (58.1 gm)~Butylated Hydroxy Toluene ( 0.2mg)~Magnesium Stearate (3mg)~Gelatin Capsule Shell (1mg)~80.000IU/week,orally,for 90 days | Drug: Cholecalciferol<br>* • Cholecalciferol (40,000IU),~,Microcrystalline Cellulose (58.1 gm), Butylated Hydroxy Toluene ( 0.2mg),Magnesium Stearate (3mg),Gelatin Capsule Shell (1mg)<br>* Other names: Magnesium Stearate (3mg);|
| Active Comparator: B90<br>B90- On day 90,after intervention cholecalciferol,~Cholecalciferol (40,000IU)~Microcrystalline Cellulose (58.1 gm)~Butylated Hydroxy Toluene ( 0.2mg)~Magnesium Stearate (3mg)~Gelatin Capsule Shell (1mg)~80.000IU/week,orally,for 90 days | Drug: Cholecalciferol<br>* • Cholecalciferol (40,000IU),~,Microcrystalline Cellulose (58.1 gm), Butylated Hydroxy Toluene ( 0.2mg),Magnesium Stearate (3mg),Gelatin Capsule Shell (1mg)<br>* Other names: Magnesium Stearate (3mg);|
|
Effect of Vitamin D3 on Lung Function and Exercise Tolerance in COPD Patients
Study Overview
=================
Brief Summary
-----------------
Background: Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality throughout the world which is a preventable as well as treatable disease. It has some important extra pulmonary effects which may contribute to the magnitude of the severity of this disease. Standard therapeutic treatment alone does not optimize its remedy. Vitamin D3 has been found to improve the physical efficiency of patients with various morbid disorders, including respiratory ailments. Hypothesis:Vitamin D3 administration in stable patients with moderate COPD improves lung function variables along with exercise tolerance. Objectives: To evaluate the effects of Vitamin D3 on lung functions and exercise tolerance in patients with stable moderate COPD. Methods: For this, a prospective interventional randomized double blinded study will be carried out on 46 vitamin D3 deficient (serum 25 dihidroxycholecalceferol less than 30 ng/ml), male, stable (diagnosed patient, who has not experienced any acute exacerbation , hospitalizations , urgent care visits, or changes in routine medication within 4 weeks prior to study), moderate (post bronchodilator FEV1/FVC<0.70 of predicted value and FEV1=50 to 79% of predicted value) COPD patients (age ≥40 years), who will be selected from the Out Patient Department (OPD) of the National Institute of Diseases of Chest and Hospital (NIDCH) and will be grouped as A (control) and B (study) groups, respectively. All the patients will be again designated as A0, A90 (without D3) and B0, B90 (with D3) for before and after 90 days of follow up. All the participants will be matched in terms of duration of COPD, history of smoking, occupation and socioeconomic status. Along with the standard pharmacological treatment of COPD, the patients of the 'Study group' will be prescribed for 80000 IU of oral vitamin D3 pre week for consecutive 3 months. Along with this, all patients both the groups will be advised to continue ad lib (according to their own choice) diet. At the very 1st day of the study, the lung functions will be assessed by measuring Forced vital capacity (FVC), Forced expiratory volume in one second (FEV1), Forced expiratory ratio (FEV1/FVC%), Peak expiratory flow rate (PEFR) and Forced mid expiratory flow of FVC(FEF25-75%), with a portable digital spirometer. In addition, exercise tolerance will be assessed by change in 6 Minute Walk Distance (6MWD) in 6 Minute Walk Test (6MWT). Changes in peripheral capillary oxygen saturation (SpO2) by Pulse Oximeter and degree of dyspnoea by Modified Borg Scale (MBS) will also be measured both before and after 6MWT to evaluate their change in both the groups. All these variables will be measured again among same 46 patient after 90 days standard pharmacological treatment of COPD with D3 intervention (B group) and also without D3 intervention (A group). For statistical analysis, Chi-square test, independent sample 't' test between two groups, paired Student's 't' test within two specific measurements of different durations of each group ,will be done. In the interpretation of results, ≤0.05 level of probability (p) will be accepted as significant.
Detailed Description
-----------------
Introduction: Chronic Obstructive Pulmonary Disease (COPD) is one of the major causes of chronic morbidity and mortality throughout the world . Many people suffer from the disease for years and die too early from its complications. COPD is the fourth leading cause of death in adults of United States and also projected to be the third by 2020 .Though it is a preventable and treatable disease, once developed the disease along with its comorbidities cannot be cured. But its progression and morbidity can be reduced. The airflow obstruction in this disease is generally persistent as well as progressive .It has two clinical phases (stable phase and exacerbation phase), both of which are associated with inflammation .Independent risk factors for COPD are male gender, advanced age, low socioeconomic status, occupational exposure and cigarette smoking (both active and passive) ,reactivity of airways, occupational factors and air pollution . Vitamin D is a steroid important in bone mineralization and calcium homeostasis. The prevalence of vitamin D deficiency has been increasing in the general population in recent decades. The majority of circulating 25-hydroxyvitamin D [25(OH)D] is derived from sun exposure with a limited dietary contribution. The increased prevalence of vitamin D deficiency is attributed to sun avoidance, indoor lifestyle, use of sunscreen, and decreased intake of vitamin D-containing foods .Because vitamin D is sequestered in adipose tissue, the increasing prevalence of obesity also increases the prevalence of vitamin D deficiency . Recently, research has found that vitamin D may play a role in multiple chronic diseases such as cancer, autoimmune diseases, infections, and cardiovascular disorders . Vitamin D may also have a role in several diseases involving the respiratory system. Recently some researchers reported that a significant proportion of young COPD patients may have insufficient (20 to 29 ng/ml) serum 25-OHD . Moreover, higher serum vitamin D concentrations, assessed by [25(OH)D], have been associated with better lung function as measured by FEV1 in a large cross-sectional study of the U.S. population . Although the precise connection between vitamin D status and lung function is not clear at this point, it is postulated that vitamin D may improve lung function through its action on regulating inflammation ,inducing antimicrobial peptides , and/or its action on muscles . It has also been suggested that, patients with COPD have a high prevalence of vitamin D deficiency, ranging from approximately 30% in mild COPD to over 75% in severe COPD. Particularly for COPD, vitamin D deficiency may enhance chronic airway and systemic inflammation, reduce bacterial clearance, and increase the risk for infectious exacerbations at the same time . To provide a quick, acceptable as well as repeatable and reproducible lung function data spirometry is a safe and practical procedure .The ventilatory functions of the lung such as, forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1), FEV1/FVC ratio (FEV1/FVC %), forced mid expiratory flow rate between 25% and 75% of FVC (FEF25-75%) and peak expiratory flow rate (PEFR), can be assessed by spirometry. The indices derived from this forced exhaled maneuver have become the most accurate and reliable way of supporting a diagnosis of COPD . This test should be undertaken in all patients who may have COPD. It is needed to make a confident diagnosis as well as to exclude other diagnoses that may present with similar symptoms. Although spirometry does not fully capture the impact of COPD on a patient's health, it remains the gold standard for diagnosing the disease and monitoring its progression. It is the best standardized most reproducible and most objective measurement of airflow limitation available . In addition, oxygen saturation is an indicator of the percentage of hemoglobin saturated with oxygen at the time of the measurement. Peripheral capillary oxygen saturation values obtained from pulse oximetry (SpO2) is one part of a complete assessment of the patient's oxygenation status. Normal oxygen saturation values are 97% to 99% in the healthy individual and of 95% is clinically accepted in a patient with a normal hemoglobin level . This value may vary with the amount of oxygen utilization by the tissues. For example, in some patients, there is a difference in SpO2 values at rest compared with those during activity, such as ambulation or positioning. However it does not reflect the patient's ability to ventilate . Moreover, dyspnea is one of the most significant symptoms occurring during the progression of COPD and results from pulmonary hyperinflation, weakness of inspiratory muscles, increased ventilation, voluntary hyperventilation, increased respiratory work load and impaired function of the inspiratory muscles . The evaluation of dyspnea is very important in any chronic respiratory ailment. The effort dyspnea determined at the end of exercise is accepted as the best indicator of dyspnea .There are several scales are available to evaluate dyspnea. Though the interpretation of dyspnea scales depends solely on the statements of the patients, but Modified Borg Scale (MBS) is known to be simple and partially objective, have usually been used to evaluate effort dyspnea in clinical practice . Respiratory disease often presents with limited activity level and exercise capacity and reduced exercise tolerance is a hallmark of patients with COPD . In 1963, Balke developed a simple test to evaluate the functional capacity by measuring the distance walked during a period of time. Walk test are typically administered as a means of evaluating functional status, monitoring treatment effectiveness and establishing prognosis. The 6 minutes walk test (6 MWT) is a practical simple test that requires a 30 meter hallway but no exercise equipment or advance training for the observer. The test measures the distance that a person can quickly walk on a flat, hard surface in a period of 6 minutes. The self paced 6 MWT assesses the submaximal level of functional capacity. However, because most activities of daily living are performed at submaximal levels of exertion, the 6 minutes walk distance (6 MWD) may better reflect the functional exercise level for daily physical activities. Rationale: Standard therapeutic treatment schedule has a limited role in improving the physical capacity in COPD patients .Various supplementations and extra-therapeutic measures have been tried to improve the functional capacity of the COPD patients . Vitamin D3 supplementation is one of them. The principal goals of adding vitamin D3 in the treatment schedule of these patients are to reduce symptoms and exacerbations, to improve quality of life and to increase physical and emotional participation in everyday activities which may not be adequately addressed by standard pharmacological regime alone for COPD .Recently, a number of studies have shown an association between vitamin D deficiency and severity of COPD . In addition in a prospective study, FEV1 was measured in patients with severe and very severe COPD both before and after vitamin D3 supplementation and significant improvement was found .On the other hand, one recent study reported no significant improvement in FVC, FEV1 and FEV1/FVC% in Vitamin D3 insufficient COPD patients after vitamin D3 administration as compared to that of the control group . However the volume of information regarding the effect of vitamin D3 administration in COPD patients is not enough for reaching any final conclusion. Moreover, with the best of our knowledge no study have been conducted to observe the effects of this fat soluble vitamin on the spirometric lung function status, oxygen saturation and exercise tolerance in vitamin D3 insufficient, stable patients with moderate COPD. Therefore, on the basis of this background the present study has been designed to evaluate the effects of Vitamin D3 on the spirometric lung function status, peripheral capillary oxygen saturation and exercise tolerance in D3 insuffucient, male patients with stable moderate COPD. This study will draw attention of the physicians about the beneficial effects of the vitamin D3 on both pulmonary and extrapulmonary complications in COPD patients. Research Question: Does vitamin D3 has any effect on lung function and exercise tolerance in stable COPD patients? Hypothesis: Vitamin D3 administration in stable patients with moderate COPD improves lung function variables along with exercise tolerance. Objectives: General Objective To evaluate the effects of vitamin D3 administration on lung functions and exercise tolerance in vitamin D3 insufficient male patients with stable moderate COPD. Specific Objectives To measure the FVC, FEV1, FEV1/FVC%, PEFR and FEF25-75% of vitamin D3 insufficient male patients with stable moderate COPD, in order to assess their lung function status. To measure the SpO2 at rest, in order to assess the basal oxygenation status in this group of patients. To determine level of dyspnea at rest, in order to assess the basal breathlessness level in the same group of patients To measure the 6MWD of all the patients, in order to assess their functional exercise capacity. To measure both the SpO2 and level of dyspnea again after 6MWT, for the assessment of their exercise tolerance. To measure all these variables after 90 days standard pharmacological treatment with vitamin D3 and also without vitamin D3 in stable COPD patients. To compare the results of baseline and endline. Methodology: TYPE OF STUDY : Prospective interventional randomized double blinded study PLACE OF STUDY : Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka STUDY PERIOD : March 2017 to February 2018 STUDY POPULATION : Stable, moderate COPD patients with vitamin D3 insufficiency. SAMPLE SIZE : 46 SAMPLING : Simple random sampling . According to the selection criteria total 46 COPD patients suitable for the aims and objectives of the study, will be enrolled. 46 patients of COPD will be selected by clinician in OPD. GROUPING OF THE SUBJECTS : Group A (Control group) : 23 D3 insufficient COPD patients without D3 administration A0 : On day 0 A90 : On day 90 Group B (Study group) : 43 (forty three) D3 insufficient COPD patients with D3 administration B0 : On day 0 B90 : On day 90 Sample size calculation: Using the following statistical formula n = (Zα+Zβ) 2 X (σ12+σ22) (μ1-μ2)2 Here, Using the following statistical formula n = [(Zα+Zβ)2 X (σ12+σ22)] / (μ1-μ2)2 Mean of control, μ1 = 47.1 Mean of study group, μ2 = 67.4 SD of control, σ1 = 26.9 SD of study group, σ2 = 27.5 (Martineau et al. 2015) Type I Error, Zα = 1.96 Type II Error, Zβ = 1.64 (Kirkwood and Sterne 2003) (Kirkwood and Sterne 2003) Therefore, n = [(Zα+Zβ)2 X (σ12+σ22)] / (μ1-μ2)2 [(1.96+1.64)2 X (26.92 +27.52) / (47.1-67.4)2 [12.96 X (756.25+723.61)] / (20.3) 2 = 19178.98 / 412.09 = 46.54 = 47 Subject Selection: After selection of subject the researcher will sit for an interview with the subject. The researcher will at first introduce himself mentioning his institutional affiliation, conflict of interest and will supply address, contact telephone number and information about sponsorship. After that the subject will be thoroughly informed about the objectives and outcome of the study. Brief explanation of the procedure will be given to them. The subject will also be assured if any problem arises during the test; it will be taken care of. The result of the test will be sent to him free of charge and if any abnormality is detected, then appropriate management will be given to him, if possible or will be referred to specific treatment facility as appropriate. He will be encouraged for voluntary participation in a cordial and friendly attitude and will be allowed freedom to withdraw from the study whenever he likes even after participation. They will be informed about the method of confidentiality of their identification. Their identity will be recorded only in questionnaire which will be kept in safe custody with the researcher. It will not enter in the computer and will not go in any publication. No personal identification will be used in data analysis, report writing or publication. They will also be assured that interview time will minimum for maintaining their comfort, some questions will be asked about the personal, family and medical history without any private enquiry. The conflict of interest will be told to him if there is any. After he has understood these entire procedure, if he agrees to participate, then a willingly given informed written consent will be taken from him. There is no possibility of any physical, social or mental risk of the respondent. A pretested questionnaire will be filled up by the research assistant. All gathered information will be kept secret and only will be used for medical research and analysis. SITE OF SAMPLE COLLECTION: All the patients will be collected from the Out Patient Department (OPD) of National Institute of Diseases of Chest and Hospital STUDY PROCEDURE: On the first day of enrollment, the objectives, nature, purpose and potential risk of all the procedures used for the study will be explained in detail to each subject, with a cordial attitude giving emphasis on the benefits he might obtain from this study. He will be encouraged for voluntary participation and will be allowed to withdraw himself from the study even after participation, whenever he felt uneasy. If he agreed to be enrolled in the study, an informed written consent will be taken in a prescribed form . Detailed family history, medical history and thorough physical examination of each patient will be done and all the information will be recorded in a standard data sheet . Then all the patients will be requested to attend the Department of Physiology at 9 am (about 1 and 1/2 hours after his breakfast) on the day of biochemical and spirometric examination. On the examination day, 5 ml of venous blood will be collected and taken to the Hematology laboratory as soon as possible for the estimation of serum 25-hydroxycholecalceferol, serum glucose 2 hours after breakfast and serum creatinine. After that his height and weight will be measured and the spirometric lung function test will be done by using a portable spirometer. After getting all the biochemical and spirometric reports the final selection will be done, according to the inclusion and exclusion criteria. Subsequently, all the eligible patients will be randomly assigned to either 'Control' or 'Study' groups and will be thoroughly informed about the objectives and detailed study procedure, once again. Then the patients will be examined for the baseline value of all the study variables in Day 1. Again after 90 days the study variables will be collected from same 86 patients. Vitamin D3 Ingredient Cholecalciferol (40,000IU) Microcrystalline Cellulose (58.1 gm) Butylated Hydroxy Toluene ( 0.2mg) Magnesium Stearate (3mg) Gelatin Capsule Shell (1mg) Dose : 80,000 IU/wk Route : Oral Placebo : Courtesy of Beximco Pharmaceuticals Limited Bangladesh Ingredient : • Microcrystalline Cellulose (303.8gm) Butylated Hydroxy Toluene (0.2mg) Magnesium Stearate (3mg) Gelatin Capsule Shell (1mg) STUDY VARIABLES: Spirometric variables • FVC (L) : Forced Vital Capacity • FEV1 (L) : Forced Expiratory Volume in 1st second FEV1/FVC Ratio (%) : Forced Expiratory Ratio PEFR (L/min) : Peak Expiratory Flow Rate FEF 25-75 (L/S) : Forced Expiratory Flow in the middle of FVC Oxygenation variables • Resting SpO2 (%) : Resting Peripheral Capillary Oxygen saturation Exercise tolerance variables • 6MWD (meter) : Six Minute Walk Distance • Level of Dyspnea : Modified Borg Scale Hematological variables • 25(OH)D (ng/ml) : 25-hydroxycholecalceferol • PTH (pmol/l) : Parathyroid hormone • Ca2+ (mg/ml) : Ionic calcium • PO43- (mg/ml) Ionic phosphate AP (U/L) : Alkaline Phosphatase Subsequently a standard therapeutic treatment will be prescribed to all the selected stable moderate COPD patients. In addition, the patients of the 'Study group' will be prescribed for 80000 IU of oral vitamin D3 per week for consecutive 90 days . Along with this, all the patients of both the groups will be advised to continue ad lib (according to their own choice) diet. Proper education will be given about drug , method of taking medication and medication plan.Afterwards,a good rapport will be built up to take time to time follow up over telephone and visiting patient's place .Schedule appointment ,hotline and follow up will be maintained properly. They will be requested to attend the Department of Physiology again on the 90th day, to have the assessment of all the above-mentioned study variables Any patient, who failed to follow the study procedure exactly during study period, will be dropped and a new one will be included to fulfill the desired total sample number.Thats why extended sample should be taken to fulfill the total sample number.
Official Title
-----------------
Effect of Vitamin D3 on Lung Function and Exercise Tolerance in D3 Deficient COPD Patients
Conditions
-----------------
Stable COPD Patients
Intervention / Treatment
-----------------
* Drug: Cholecalciferol
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Socioeconomic status: Middle class Smoker Stable patients of COPD with >1year duration Vitamin D3 deficient : Serum 25-hydroxycholecalciferol, [25(OH)D] level <30ng/ml (Vitamin D Council 2017) Exclusion Criteria: With acute exacerbation of any pulmonary diseases, as, with acute exacerbation of any cardiac disease, like - Uncontrolled systemic hypertension Chronic liver disease Malignancy Use of drugs known to affect vitamin D metabolism within 1 month prior to With biochemical evidence of - uncontrolled diabetes mellitus and renal insufficiency All the criteria mentioned above were scrutinized by taking history and clinical examination, except vitamin D3 deficiency, uncontrolled diabetes mellitus and renal insufficiency, which were diagnosed biochemically.
Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two groups of Vitamin D3 deficient stable COPD patients were taken, Group A was given placebo along with standard therapeutic treatment and Group B was given Vitamin D3 along with standard therapeutic treatment
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A0<br>A0- On day 0,before intervention placebo, Microcrystalline Cellulose (303.8gm) Butylated Hydroxy Toluene (0.2mg) Magnesium Stearate (3mg) Gelatin Capsule Shell (1mg) weekly,orally,for 90days | Drug: Cholecalciferol<br>* • Cholecalciferol (40,000IU), ,Microcrystalline Cellulose (58.1 gm), Butylated Hydroxy Toluene ( 0.2mg),Magnesium Stearate (3mg),Gelatin Capsule Shell (1mg)<br>* Other names: Magnesium Stearate (3mg);|
| Placebo Comparator: A90<br>A90- On day 90,after intervention placebo, Microcrystalline Cellulose (303.8gm) Butylated Hydroxy Toluene (0.2mg) Magnesium Stearate (3mg) Gelatin Capsule Shell (1mg) weekly,orally,for 90days | Drug: Cholecalciferol<br>* • Cholecalciferol (40,000IU), ,Microcrystalline Cellulose (58.1 gm), Butylated Hydroxy Toluene ( 0.2mg),Magnesium Stearate (3mg),Gelatin Capsule Shell (1mg)<br>* Other names: Magnesium Stearate (3mg);|
| Active Comparator: B0<br>B0- On day 0,before intervention cholecalciferol, Cholecalciferol (40,000IU) Microcrystalline Cellulose (58.1 gm) Butylated Hydroxy Toluene ( 0.2mg) Magnesium Stearate (3mg) Gelatin Capsule Shell (1mg) 80.000IU/week,orally,for 90 days | Drug: Cholecalciferol<br>* • Cholecalciferol (40,000IU), ,Microcrystalline Cellulose (58.1 gm), Butylated Hydroxy Toluene ( 0.2mg),Magnesium Stearate (3mg),Gelatin Capsule Shell (1mg)<br>* Other names: Magnesium Stearate (3mg);|
| Active Comparator: B90<br>B90- On day 90,after intervention cholecalciferol, Cholecalciferol (40,000IU) Microcrystalline Cellulose (58.1 gm) Butylated Hydroxy Toluene ( 0.2mg) Magnesium Stearate (3mg) Gelatin Capsule Shell (1mg) 80.000IU/week,orally,for 90 days | Drug: Cholecalciferol<br>* • Cholecalciferol (40,000IU), ,Microcrystalline Cellulose (58.1 gm), Butylated Hydroxy Toluene ( 0.2mg),Magnesium Stearate (3mg),Gelatin Capsule Shell (1mg)<br>* Other names: Magnesium Stearate (3mg);|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung function (Spirometric variables) Forced Vital Capacity(FVC) will be changed | Forced Vital Capacity It is the volume of air that can be expired as forcefully and rapidly as possible after maximal inspiration. In adult male it is about 4.6 liters. The FVC is commonly reduced in obstructive processes such as COPD.Increment of Forced Vital Capacity means improvement in outcome. | After 90 days FVC will be measured again |
| Lung function [ Lung function (Spirometric variables): Forced Expiratory Volume in 1st second(FEV1) will be changed | Forced Expiratory Volume in 1st second When a person inspires maximally and exhales forcefully, then the volume, which is exhaled in 1st second is known as 'Forced Expiratory volume in 1st second'. It is normally 80% of forced vital capacity . Significance- This measurement is much more sensitive index of severity of the obstructive disease .In COPD ,FEV1 is reduced ,Increment of FEV1 indicates improvent in outcome | After 90 days FEV1 will be measured again |
| Lung function (Spirometric variables) Forced Expiratory Ratio [FEV1/FVC Ratio (%)] will be changed | Forced Expiratory Ratio It is the ratio of FEV1 to FVC expressed in percentage. FEV1/FVC ratio = FEV1/FVC×100. It is about 70% or higher. Forced Expiratory Ratio is less than 70% in COPD patients.Increment of Forced Expiratory Ratio indicates improvement in outcome | After 90 days FEV1/FVC Ratio will be measured again |
| Lung function (Spirometric variables) Peak Expiratory Flow Rate [PEFR (L/min)] will be changed | Peak Expiratory Flow Rate It is the maximum expiratory rate, beyond which the flow cannot be increased even with greatly increased additional force. In adult it is about 400-700 Liter/second. | After 90 days PEFR will be measured again |
| Lung function (Spirometric variables) Forced Expiratory Flow in the middle of FVC [FEF 25-75 (Liter/Second) ] will be changed | Forced Expiratory Flow in the middle of FVC Forced expiratory flow during the middle half of the FVC. Formerly it was called the maximal mid-expiratory flow (MMEF), expressed in liters/second Normal range in male : 1.5-4.5 Liter/second.Increment of Forced Expiratory Flow in the middle of FVC means improvement in outcome. | After 90 days FEF 25-75 will be measured again |
| Lung function (Spirometric variables) Maximum expiratory Flow rate at 25%of the FVC (MEF 75) will be changed | Maximum expiratory Flow rate at 25%of the FVC (MEF 75) Maximum expiratory flow rate when 25% of the FVC remains in the lung to be exhaled and is equivalent to the FEF75 where 75% of the FVC has been exhaled. Expressed in liters/second. This is reduced in COPD. Increment in maximum expiratory flow at 25%of the FVC means improvement in outcome | After 90 days MEF 75 will be measured again |
| Lung function (Spirometric variables) Maximum expiratory Flow at 50%of the FVC(MEF50) will be changed | Maximum expiratory Flow at 50%of the FVC(MEF50) Maximum expiratory flow rate when 50 % of the FVC remains in the lung to be exhaled and is equivalent to the FEF50 where 50% of the FVC has been exhaled. Expressed in liters/second. This is reduced in COPD. Increment in maximum expiratory flow at 50%of the FVC means improvement in outcome. | After 90 days MEF 50 will be measured again |
| Lung function (Spirometric variables) Maximum expiratory Flow at 75%of the FVC (MEF25)]will be changed | Maximum expiratory Flow at 75%of the FVC (MEF25) Maximum expiratory flow rate when 75% of the FVC remains in the lung to be exhaled and is equivalent to the FEF25 where 25% of the FVC has been exhaled. Expressed in liters/second.This is reduced in COPD.Increment in maximum expiratory flow at 75%of the FVC means improvement in outcome | After 90 days MEF25 will be measured again |
| Exercise Tolerance [Oxygenation variables] Peripheral Capillary Oxygen saturation[SpO2 (%) ] will be changed | Oxygenation variables Peripheral Capillary Oxygen saturation between 96% to 99% is normal.Peripheral Capillary Oxygen saturation between 96% to 99% means improved outcome | After 90 days SpO2 will be measured |
| Exercise Tolerance Exercise tolerance variables •Six Minute Walk Distance[6MWD (meter) ]will be changed | Exercise tolerance variables • Six Minute Walk Distance [6MWD (meter) ] minimum 350m in 6minute at a time(without taking any rest) is standard.The more the distance,the more the better outcome. | After 90 days 6MWD will be measured |
| Exercise Tolerance variables • Level of Dyspnea : Modified Borg Scale will be changed | Level of Dyspnea : Modified Borg Scale If the dyspnea score decreases,it means better outcome If the dyspnea score increases,it means outcome is worse | After 90 days level of Dyspnea will be measured |
| Exercise Tolerance variables Level of fatigue: Modified Borg Scale will be changed | Level of fatigue: Modified Borg Scale If the fatigue score decreases,it means better outcome, If the fatigue score increases,it means outcome is worse | After 90 days level of fatigue will be measured |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD, VitaminD3, 6 Minute Walk Distance, Modified BORG scale
|
|
NCT05737472
|
High-protein Quantity and Quality RUTF in Improving Linear Growth Among Children With Severe Wasting
|
This is a proof-of-concept trial that aims to compare the efficacy of an 8-week treatment with higher-protein-Ready-to-Use Therapeutic Foods (RUTF) with standard RUTF in improving levels of markers of growths, height, nutritional recovery, and lean mass deposition among children with severe wasting. The study will also assess the safety and acceptability of the high-protein RUTF in comparison to the standard RUTF. The study will be conducted at four outpatient therapeutic programs in the Blantyre district of Malawi.
|
RUTF has successfully promoted recovery from severe wasting and widened treatment coverage. However, RUTF does not sufficiently promote linear growth, leaving many survivors of severe wasting at risk of persistent stunting. Stunting is associated with long-term effects like poor child development and an increased risk of non-communicable diseases in adults. High protein quantity and quality are known to stimulate linear growth; however, an RUTF with a higher protein quantity and quality than the standard RUTF has yet to be tested. The investigators hypothesize that the suboptimal linear growth in children surviving severe malnutrition can be improved by increasing the protein quantity and quality in the standard RUTF formulation. The investigators have designed a high protein quantity and quality RUTF that will be tested in a proof-of-concept quadruple-blind randomised controlled trial study design. The trial aims to compare the efficacy of higher-protein-RUTF and standard RUTF in improving markers of linear growth among 6-23 months old children with severe wasting.~Children aged 6-23 months newly enrolled in outpatient treatment programs for severe wasting and without medical complications are eligible. They will be assigned to either increased protein RUTF or standard RUTF for eight weeks.~The primary outcome is a change in insulin-like growth factor-1 (IGF- 1) after four weeks of treatment. IGF-1 is a hormone that is mechanistically linked with growth. Secondary outcomes include ponderal and linear growth changes from baseline measured at eight weeks and plasma amino acid profile at four weeks. Other secondary outcomes are the acceptability and safety of high protein RUTF compared to standard RUTF. These findings will help to determine the optimal protein composition of RUTF to promote linear growth when treating severe wasting in children.
|
A Proof-of-concept Randomized Control Trial on the Role of Higher Protein Quantity and Quality-ready-to-use Therapeutic Food in Improving Linear Growth Among 6-23-month-old Children With Severe Wasting
|
Severe Wasting, Severe Acute Malnutrition
|
* Dietary Supplement: High-protein RUTF
* Dietary Supplement: Standard RUTF
|
Inclusion Criteria:~Infants 6-23 months of age with severe wasting at OTP admission according to the WHO criteria: WHZ below -3 or MUAC below 115mm.~Parent or guardian is able and available to consent~Children who are able to feed orally in the usual state of health~The primary caregiver plans to stay in the study area during the duration of the study.~Exclusion Criteria:~Children with medical complications as per the CMAM guidelines (lack of appetite, severe oedematous malnutrition, acute infections)~mild and moderate nutritional oedema~Children with a known terminal illness (e.g. cancer), cerebral palsy (CP), tuberculosis (TB,) HIV infected or exposed~Children who had SAM in the last 8 weeks, i.e., SAM relapses in the last 8 weeks~Children admitted to any NRU due to complicated SAM in the previous 4 weeks will also be excluded~Children whose caregivers refuse to give consent or whose primary givers are not available to give consent~Children who were previously enrolled in this trial or currently enrolled in this trial whose sibling has also been enrolled in the study~Children with known intolerance or allergy to high protein diets will be excluded as well as known intolerance or allergy to milk/lactose
|
6 Months
|
23 Months
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma IGF-1 | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in increasing circulating IGF- 1 in 6-23-month-old children with severe wasting. | 4 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in height for age z score | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in height-for-age z score. | 8 weeks |
| Changes in weight for age z score | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in weight for age z score | 8 weeks |
| Changes in weight for height z score | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in weight for height z score | 8 weeks |
| Changes in knee heel length | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in knee heel length | 8 weeks |
| Changes in plasma essential amino acid profile leucine, threonine and tryptophan | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving plasma essential amino acids: leucine, threonine and tryptophan | 4 weeks |
| Changes in IGFBP3 | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in increasing IGFFBP3 | 4 weeks |
| Changes in fat free mass accretion | • To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving fat free mass accretions (kg/m2) using bioelectrical impedance and skinfold thickness | 8 weeks |
| Changes in fat mass accretion | • To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving fat mass accretion (kg/m2) using bio-electrical impedance assessment and skinfold thickness | 8 weeks |
| Acceptability of high-protein RUTF | • To assess acceptability of the high protein RUTF formulation compared to standard RUTF among children with severe wasting using an adaptation of action against hunger RUTF apettite test | 4 |
| Acceptability of high-protein RUTF | • To assess acceptability of the high protein RUTF formulation compared to standard RUTF among children with severe wasting by observing RUTF intake at participant homes for 5 hours at a single time point | 4 |
| Compliance of high-protein RUTF | • To assess compliance of the high protein RUTF formulation compared to standard RUTF among children with severe wasting by conducting in-depth interviews with the caregivers | 4 |
| Safety of the high protein RUTF formulation:adverse events | To assess the safety of high-protein-RUTF compared to standard RUTF by recording adverse events (defined as any untoward event including morbidity reported by the participant or detected by the investigator) | 8 weeks |
| Safety of the high protein RUTF formulation: severe adverse events | To assess the safety of high-protein-RUTF compared to standard RUTF by recording adverse events (defined as any life threatening event reported by the participant or detected by the investigator) | 8 weeks |
|
RUTF, Child health, Ready-to-use therapeutic food, Severe acute malnutrition, Wasting, Outpatient Therapeutic Programme, OTP, SAM
|
Malnutrition, Wasting Syndrome, Severe Acute Malnutrition, Cachexia, Nutrition Disorders, Weight Loss, Body Weight Changes, Body Weight, Thinness, Metabolic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard RUTF<br>The standard RUTF dose is according to weight as per the WHO 2013 guideline, thus 150-220Kcal/kg/day. A child will receive a weekly ration for 8 consecutive weeks from enrolment. | Dietary Supplement: Standard RUTF<br>* The standard RUTF was manufactured according to WHO recommendations, with at least 50% of protein-sourced dairy, mainly skim milk. A total of 10% of energy is from protein. The protein quality score, digestible indispensable amino acid score (DIAAS) of the standard RUTF is 0.76, which is equivalent to a Protein Digestibility Corrected Amino Acid Score (PDCAAS) of 0.86.<br>|
| Experimental: High-protein RUTF<br>The high-protein RUTF dose is according to weight as per the WHO 2013 guideline, thus 150-220Kcal/kg/day. A child will receive a weekly ration for 8 consecutive weeks from enrolment. | Dietary Supplement: High-protein RUTF<br>* The high-protein RUTF is isocaloric to the standard RUTF. To have a higher protein quantity and quality, the recipe has greater proportions of milk powder plus whey protein and vegetable oil. A total of 15% of energy is from protein. The protein quality score, digestible indispensable amino acid score (DIAAS )of the high protein, RUTF is 1.18 which is equivalent to a Protein Digestibility Corrected Amino Acid Score (PDCAAS) of 1.19<br>|
|
High-protein Quantity and Quality RUTF in Improving Linear Growth Among Children With Severe Wasting
Study Overview
=================
Brief Summary
-----------------
This is a proof-of-concept trial that aims to compare the efficacy of an 8-week treatment with higher-protein-Ready-to-Use Therapeutic Foods (RUTF) with standard RUTF in improving levels of markers of growths, height, nutritional recovery, and lean mass deposition among children with severe wasting. The study will also assess the safety and acceptability of the high-protein RUTF in comparison to the standard RUTF. The study will be conducted at four outpatient therapeutic programs in the Blantyre district of Malawi.
Detailed Description
-----------------
RUTF has successfully promoted recovery from severe wasting and widened treatment coverage. However, RUTF does not sufficiently promote linear growth, leaving many survivors of severe wasting at risk of persistent stunting. Stunting is associated with long-term effects like poor child development and an increased risk of non-communicable diseases in adults. High protein quantity and quality are known to stimulate linear growth; however, an RUTF with a higher protein quantity and quality than the standard RUTF has yet to be tested. The investigators hypothesize that the suboptimal linear growth in children surviving severe malnutrition can be improved by increasing the protein quantity and quality in the standard RUTF formulation. The investigators have designed a high protein quantity and quality RUTF that will be tested in a proof-of-concept quadruple-blind randomised controlled trial study design. The trial aims to compare the efficacy of higher-protein-RUTF and standard RUTF in improving markers of linear growth among 6-23 months old children with severe wasting. Children aged 6-23 months newly enrolled in outpatient treatment programs for severe wasting and without medical complications are eligible. They will be assigned to either increased protein RUTF or standard RUTF for eight weeks. The primary outcome is a change in insulin-like growth factor-1 (IGF- 1) after four weeks of treatment. IGF-1 is a hormone that is mechanistically linked with growth. Secondary outcomes include ponderal and linear growth changes from baseline measured at eight weeks and plasma amino acid profile at four weeks. Other secondary outcomes are the acceptability and safety of high protein RUTF compared to standard RUTF. These findings will help to determine the optimal protein composition of RUTF to promote linear growth when treating severe wasting in children.
Official Title
-----------------
A Proof-of-concept Randomized Control Trial on the Role of Higher Protein Quantity and Quality-ready-to-use Therapeutic Food in Improving Linear Growth Among 6-23-month-old Children With Severe Wasting
Conditions
-----------------
Severe Wasting, Severe Acute Malnutrition
Intervention / Treatment
-----------------
* Dietary Supplement: High-protein RUTF
* Dietary Supplement: Standard RUTF
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infants 6-23 months of age with severe wasting at OTP admission according to the WHO criteria: WHZ below -3 or MUAC below 115mm. Parent or guardian is able and available to consent Children who are able to feed orally in the usual state of health The primary caregiver plans to stay in the study area during the duration of the study. Exclusion Criteria: Children with medical complications as per the CMAM guidelines (lack of appetite, severe oedematous malnutrition, acute infections) mild and moderate nutritional oedema Children with a known terminal illness (e.g. cancer), cerebral palsy (CP), tuberculosis (TB,) HIV infected or exposed Children who had SAM in the last 8 weeks, i.e., SAM relapses in the last 8 weeks Children admitted to any NRU due to complicated SAM in the previous 4 weeks will also be excluded Children whose caregivers refuse to give consent or whose primary givers are not available to give consent Children who were previously enrolled in this trial or currently enrolled in this trial whose sibling has also been enrolled in the study Children with known intolerance or allergy to high protein diets will be excluded as well as known intolerance or allergy to milk/lactose
Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 23 Months
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard RUTF<br>The standard RUTF dose is according to weight as per the WHO 2013 guideline, thus 150-220Kcal/kg/day. A child will receive a weekly ration for 8 consecutive weeks from enrolment. | Dietary Supplement: Standard RUTF<br>* The standard RUTF was manufactured according to WHO recommendations, with at least 50% of protein-sourced dairy, mainly skim milk. A total of 10% of energy is from protein. The protein quality score, digestible indispensable amino acid score (DIAAS) of the standard RUTF is 0.76, which is equivalent to a Protein Digestibility Corrected Amino Acid Score (PDCAAS) of 0.86.<br>|
| Experimental: High-protein RUTF<br>The high-protein RUTF dose is according to weight as per the WHO 2013 guideline, thus 150-220Kcal/kg/day. A child will receive a weekly ration for 8 consecutive weeks from enrolment. | Dietary Supplement: High-protein RUTF<br>* The high-protein RUTF is isocaloric to the standard RUTF. To have a higher protein quantity and quality, the recipe has greater proportions of milk powder plus whey protein and vegetable oil. A total of 15% of energy is from protein. The protein quality score, digestible indispensable amino acid score (DIAAS )of the high protein, RUTF is 1.18 which is equivalent to a Protein Digestibility Corrected Amino Acid Score (PDCAAS) of 1.19<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma IGF-1 | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in increasing circulating IGF- 1 in 6-23-month-old children with severe wasting. | 4 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in height for age z score | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in height-for-age z score. | 8 weeks |
| Changes in weight for age z score | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in weight for age z score | 8 weeks |
| Changes in weight for height z score | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in weight for height z score | 8 weeks |
| Changes in knee heel length | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in knee heel length | 8 weeks |
| Changes in plasma essential amino acid profile leucine, threonine and tryptophan | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving plasma essential amino acids: leucine, threonine and tryptophan | 4 weeks |
| Changes in IGFBP3 | To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in increasing IGFFBP3 | 4 weeks |
| Changes in fat free mass accretion | • To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving fat free mass accretions (kg/m2) using bioelectrical impedance and skinfold thickness | 8 weeks |
| Changes in fat mass accretion | • To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving fat mass accretion (kg/m2) using bio-electrical impedance assessment and skinfold thickness | 8 weeks |
| Acceptability of high-protein RUTF | • To assess acceptability of the high protein RUTF formulation compared to standard RUTF among children with severe wasting using an adaptation of action against hunger RUTF apettite test | 4 |
| Acceptability of high-protein RUTF | • To assess acceptability of the high protein RUTF formulation compared to standard RUTF among children with severe wasting by observing RUTF intake at participant homes for 5 hours at a single time point | 4 |
| Compliance of high-protein RUTF | • To assess compliance of the high protein RUTF formulation compared to standard RUTF among children with severe wasting by conducting in-depth interviews with the caregivers | 4 |
| Safety of the high protein RUTF formulation:adverse events | To assess the safety of high-protein-RUTF compared to standard RUTF by recording adverse events (defined as any untoward event including morbidity reported by the participant or detected by the investigator) | 8 weeks |
| Safety of the high protein RUTF formulation: severe adverse events | To assess the safety of high-protein-RUTF compared to standard RUTF by recording adverse events (defined as any life threatening event reported by the participant or detected by the investigator) | 8 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RUTF, Child health, Ready-to-use therapeutic food, Severe acute malnutrition, Wasting, Outpatient Therapeutic Programme, OTP, SAM
|
NCT00667875
|
An Exploratory Study of Naltrexone Plus Aripiprazole for Alcohol Dependence
|
The principal aim of this exploratory study is to examine whether the addition of aripiprazole to naltrexone will enhance efficacy over naltrexone alone in a 16-week randomized, placebo-controlled clinical trial, in which all subjects will be provided medical management as delivered in the COMBINE Study (Anton et al, 2006). To test whether medication treatment will reduce drinking compared to placebo treatment alone in the context of medical management and whether naltrexone plus aripiprazole will reduce drinking compared to naltrexone treatment alone in the context of medical management.
|
An Exploratory Study of Naltrexone Plus Aripiprazole for Alcohol Dependence
|
Alcohol Dependence
|
* Drug: Placebo
* Drug: Naltrexone
* Drug: Naltrexone + Aripiprazole
|
Inclusion Criteria:~Age 18 70~Subjects will meet criteria for primary alcohol dependence operationalized as follows:~A. Meets the DSM IV criteria for alcohol dependence including loss of control over drinking (criterion 3) B. Has not had more than one previous inpatient medical detoxification~Consumes, on average, at least 10 standard drinks per drinking day for men and 8 drinks per day for women in the 90 days pre-screening (to select an appropriately heavy drinking population)~Able to maintain sobriety for four days (with or without the aid of alcohol detoxification medications) as determined by self report, collateral report, and breathalyzer measurements~Able to read and understand questionnaires and informed consent~Lives within approximately 50 miles of the study site -~Exclusion Criteria:~Currently meets DSM IV criteria for any other psychoactive substance dependency disorder except nicotine dependence~Ever abused opiates~Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report, collateral report, or urine drug screen~Meets DSM IV criteria for current axis I disorders of major depression, panic disorder, obsessive compulsive disorder, post traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder~Meets DSM IV current criteria for dissociative disorder or eating disorders~Has current suicidal ideation or homicidal ideation~Need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications~Current use of disulfiram~Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit medication ingestion~Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at least 3.0 times normal at screening and/or after 5 days abstinence~Sexually active female of child-bearing potential who is pregnant (by urine HCG), nursing, or who is not using a reliable form of birth control~Has current charges pending for a violent crime (not including DUI-related offenses)~Does not have a stable living situation and a reliable source of collateral reporting~Has taken an opiate antagonist drug in the last month~Has taken aripiprazole in the last month or has experienced adverse effects from it at any time in the past
|
18 Years
|
70 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drinks Per Drinking Day | Standard drinks per drinking day | 16-week treatment period |
| Percent Heavy Drinking Days | percent of total 112 day trial in which heavy drinking occurred (>=4 for females, >=5 male) | 16 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pill Counts During Treatment | Compliance with medication as determined by pill counts | 16-week |
| Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance | Riboflavin was added to each individual capsule of medication and measured as a proxy for compliance with the medication regime | 16 weeks treatment trial |
|
Alcohol Dependence, Alcoholism, Naltrexone, Aripiprazole, Substance Abuse
|
Naltrexone, Aripiprazole, Alcohol Deterrents, Narcotic Antagonists, Physiological Effects of Drugs, Sensory System Agents, Peripheral Nervous System Agents, Antidepressive Agents, Psychotropic Drugs, Antipsychotic Agents, Tranquilizing Agents, Central Nervous System Depressants, Dopamine Agonists, Dopamine Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Serotonin 5-HT1 Receptor Agonists, Serotonin Receptor Agonists, Serotonin Agents, Serotonin 5-HT2 Receptor Antagonists, Serotonin Antagonists, Dopamine D2 Receptor Antagonists, Dopamine Antagonists
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: Placebo<br>* placebo<br>|
| Active Comparator: 2<br>Naltrexone | Drug: Naltrexone<br>* Naltrexone (25mg or 50 mg per titration schedule)<br>|
| Active Comparator: 3<br>Naltrexone + Aripiprazole | Drug: Naltrexone + Aripiprazole<br>* Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)<br>|
|
An Exploratory Study of Naltrexone Plus Aripiprazole for Alcohol Dependence
Study Overview
=================
Brief Summary
-----------------
The principal aim of this exploratory study is to examine whether the addition of aripiprazole to naltrexone will enhance efficacy over naltrexone alone in a 16-week randomized, placebo-controlled clinical trial, in which all subjects will be provided medical management as delivered in the COMBINE Study (Anton et al, 2006). To test whether medication treatment will reduce drinking compared to placebo treatment alone in the context of medical management and whether naltrexone plus aripiprazole will reduce drinking compared to naltrexone treatment alone in the context of medical management.
Official Title
-----------------
An Exploratory Study of Naltrexone Plus Aripiprazole for Alcohol Dependence
Conditions
-----------------
Alcohol Dependence
Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: Naltrexone
* Drug: Naltrexone + Aripiprazole
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 70 Subjects will meet criteria for primary alcohol dependence operationalized as follows: A. Meets the DSM IV criteria for alcohol dependence including loss of control over drinking (criterion 3) B. Has not had more than one previous inpatient medical detoxification Consumes, on average, at least 10 standard drinks per drinking day for men and 8 drinks per day for women in the 90 days pre-screening (to select an appropriately heavy drinking population) Able to maintain sobriety for four days (with or without the aid of alcohol detoxification medications) as determined by self report, collateral report, and breathalyzer measurements Able to read and understand questionnaires and informed consent Lives within approximately 50 miles of the study site - Exclusion Criteria: Currently meets DSM IV criteria for any other psychoactive substance dependency disorder except nicotine dependence Ever abused opiates Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report, collateral report, or urine drug screen Meets DSM IV criteria for current axis I disorders of major depression, panic disorder, obsessive compulsive disorder, post traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder Meets DSM IV current criteria for dissociative disorder or eating disorders Has current suicidal ideation or homicidal ideation Need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications Current use of disulfiram Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit medication ingestion Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at least 3.0 times normal at screening and/or after 5 days abstinence Sexually active female of child-bearing potential who is pregnant (by urine HCG), nursing, or who is not using a reliable form of birth control Has current charges pending for a violent crime (not including DUI-related offenses) Does not have a stable living situation and a reliable source of collateral reporting Has taken an opiate antagonist drug in the last month Has taken aripiprazole in the last month or has experienced adverse effects from it at any time in the past
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: Placebo<br>* placebo<br>|
| Active Comparator: 2<br>Naltrexone | Drug: Naltrexone<br>* Naltrexone (25mg or 50 mg per titration schedule)<br>|
| Active Comparator: 3<br>Naltrexone + Aripiprazole | Drug: Naltrexone + Aripiprazole<br>* Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drinks Per Drinking Day | Standard drinks per drinking day | 16-week treatment period |
| Percent Heavy Drinking Days | percent of total 112 day trial in which heavy drinking occurred (>=4 for females, >=5 male) | 16 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pill Counts During Treatment | Compliance with medication as determined by pill counts | 16-week |
| Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance | Riboflavin was added to each individual capsule of medication and measured as a proxy for compliance with the medication regime | 16 weeks treatment trial |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alcohol Dependence, Alcoholism, Naltrexone, Aripiprazole, Substance Abuse
|
|
NCT05068830
|
Safety and Efficacy of Plasma Transfusion From Exercise-trained Donors in Patients With Early Alzheimer's Disease
|
Introduction Given that exercise training reduces the risk of developing Alzheimer's disease (AD), induces changes in the blood composition and has widespread systemic benefits, it is reasonable to hypothesize that exercised plasma may have rejuvenative properties. The main objective is to test safety and tolerability of transfusing exercised plasma (ExPlas) from young, healthy, fit adults to patients with early AD. The study is a pilot for a future efficacy study. The key secondary objectives are examining the effect of plasma transfusions on cognitive function, fitness level, vascular risk profile, assessment of cerebral blood flow and hippocampal volume, quality of life, functional connectivity assessed by resting state functional MRI and biomarkers in blood and cerebrospinal fluid.~Methods and analysis ExPlas is a double-blinded, randomized controlled clinical single center trial. Patients aged 50-75 years with diagnosis mild cognitive impairment or early AD will be recruited from two Norwegian hospitals. ExPlas is plasma drawn by plasmapheresis once a month for 4 months, from a total of 30 donors (aged 18-40, BMI ≤27 kg/m2 and VO2max >50 mL/kg/min). All units will be virus inactivated by the Intercept method in accordance with procedures at St. Olavs Hospital. Comparison with isotonic saline allows differentiation from a non-blood product. The main study consists of 6 rounds of examinations in addition to 12 plasma transfusions divided over three 4-weeks periods during study year-1. Follow-up examinations after 2 and 5 years after baseline is also planned.~Ethics and dissemination Written informed consent will be obtained from all participants and participation is voluntary. All participants have a next of kin who will follow them throughout the study and represent the patient's interest. The study is approved by the Regional Committee for Medical and Health Research Ethics (REK 2018/702) and the Norwegian Medicines Agency (EudraCT No. 2018-000148-24).
|
Safety and Efficacy of Plasma Transfusion From Exercise-trained Donors in Patients With Early Alzheimer's Disease: The ExPlas Study
|
Alzheimer Disease
|
* Drug: ExPlas
* Drug: Octaplasma
* Drug: Saline
|
Patient inclusion criteria:~Diagnosis AD in early phase according to the IWG-2 criteria.~Mini-Mental State Examination (MMSE) Score ≥20.~In-vivo evidence of Alzheimer´s pathology (one of the following):~Decreased Aβ42 together with increased t-tau or p-tau in CSF.~Increased tracer retention on amyloid PET.~Availability of a next of kin who knows the patient well and is willing to accompany the subject to all trial visits and give information about the patients functional level.~Signed informed consent.~The patient is judged fitted for the study and capable to cooperate in treatment and follow-up.~Ability to communicate in Norwegian or another Scandinavian language.~Patient exclusion criteria:~Pregnancy or unwilling to use adequate birth control for the duration of and 6 months beyond study participation. Defined according to Clinical Trial Facilitation Group document Recommendations related to contraception and pregnancy testing in clinical trials.~Positive for Hepatitis B, Hepatitis C or HIV at screening.~Not qualified to give consent at inclusion.~Any other condition judged to interfere with the safety of the patient or the intent and conduct of the study.~Related to medical history:~Stroke~Anaphylaxis~Prior adverse reaction to any human blood product~Any history of a blood coagulation disorder or hypercoagulability~Congestive heart failure, defined as any previous heart failure hospitalization, or current symptomatic heart failure in New York heart Association class ≥II with reduced, mid-range or preserved ejection fraction.~Coagulation defect or hypercoagulopathy~Uncontrolled hypertension~Renal failure~Prior intolerance to intravenous fluids~Recent history of uncontrolled atrial fibrillation~Bone marrow transplant~IgA deficiency~Severe protein S deficiency~Thrombocytopenia (platelets < 40 x 10 to the power of 9/L)~Contraindication for Octaplasma~Related to medications or other treatments:~Any concurrent use of anticoagulant therapy, clopidogrel or acetylsalicylic acid/Dipyridamol in combination.~Initiation or change in the dosage of a acetylcholine esterase inhibitor (AChEI) or memantine during the trial (week 0-52). Participants will be urged to start on AChEI when diagnosis is communicated, and must be on a stable dose for at least one month prior to screening.~Concurrent participation in another treatment trial for AD. If there was prior participation, the last dose of the investigational agent must have been given at least 6 months prior to screening, except if the patient received placebo medication.~Treatment with any human blood product, including intravenous immunoglobulin, during the 6 months prior to screening or during the trial.~Concurrent daily treatment with benzodiazepines, typical or atypical antipsychotics, long-acting opioids, or other medications that is judged to interfere with cognition. Intermittent treatment with short-acting benzodiazepines or atypical antipsychotics may be permitted, provided that no dose is administered within 72 hours prior to cognitive assessment.~Related to magnetic resonance imaging:~Claustrophobia~Any metallic surgical implant, like a pacemaker or clip that is incompatible with MRI.~Certain metallic implants like joint replacements may be permitted, provided that specific manufacturer specifications are available, and that the device is known to be safe for 7T MRI. In case a patient is not eligible for the 7T scanner, the 3T scanner will be used.
|
50 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blinded, randomized controlled clinical phase II trial
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events | as a measure for safety and tolerability of the treatment | 1 year |
| Number of subjects who comply with the research protocol | as a measure for feasibility | 1 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CERAD-test | Change in performance in the CERAD (The Consortium to Establish a Registry for Alzheimer's Disease) Ten word Test. CERAD Word List consists of three test parts; immediate recall, delayed recall and recognition. The scoring range for immediate recall is 0-30, for delayed recall 0-10 and for recognition 0-20. Higher scores indicate better learning performance, memory performance and recognition performance. | 1, 2 and 5 years |
| MMSE | Change in the Mini-Mental State Examination Score. An MMSE score of ≥20 is criteria for inclusion. Higher scores >28 indicate normal cognitive function. Scores in the middle range 25-27 may indicate cognitive impairment. Lower scores <24 indicate cognitive impairment. | 1, 2, and 5 years |
| Trail-Making test A and B | Change in performance in Trail-Making test A and B. The Trail Making Tests are scored by how long it takes to complete the tests. Norms for completion time variate with age and educational level. Longer completion time indicates impaired visual attention, processing speed and executive function. | 1, 2, and 5 years |
| Clock Drawing Test | Change in scores in the Clock Drawing Test. The Clock Drawing Test has a scoring range 0-5. Higher scores indicate normal cognitive function. Lower scores <4 may indicate cognitive impairment, spatial dysfunction or neglect. | 1, 2, and 5 years |
| Controlled Oral Word Association Test (COWAT)-FAS | Change in scores in Controlled Oral Word Association Test (COWAT)-FAS. Scoring is based on how many words the person produces within 1 minute. The minimum score is 0, and there is no maximum score. Higher scores indicate better verbal fluency. Scoring norms are based on the persons age and education level. | 1, 2, and 5 years |
| Visual Object and Space Perception (VOSP) Silhouettes | Change in scores in Visual Object and Space Perception (VOSP) Silhouettes. Visual Object and Space Perception (VOSP) Silhouettes has a scoring range 0-30. Higher scores > 20 indicate normal visuospatial function, and lower scores < 20 indicate visuospatial dysfunction. | 1, 2, and 5 years |
| Clinical Dementia Rating Scale Global score and Sum of Boxes | Change in Clinical Dementia Rating Scale Global score and Sum of Boxes. Clinical Dementia Rating Scale (CDR) is a clinical scale for the staging of dementia. The Global Score ranges dementia severity from 0-3. The Sum of Boxes ranges dementia severity from 0-18. Higher scores indicate more severe disease. | 1, 2, and 5 years |
| The Lawton Instrumental Activities of Daily Living Scale (IADL) | Change in The Lawton Instrumental Activities of Daily Living Scale (IADL). The Lawton Instrumental Activities of Daily Living Scale (IADL) evaluates the person's ability to perform complex everyday activities. The score ranges from 8-31. Higher scores indicate lower functional level. | 1, 2, and 5 years |
| 6 minutes' walk test | Change in 6 minutes' walk-test | 1, 2, and 5 years |
| Functional MRI | Change in/Reduced hippocampal atrophy and preservation of functional connectivity assessed by resting state functional MRI. A secondary aim is to identify any effect of treatment group on MRI markers of both neurodegenerative and cerebrovascular disease. | 1, 2, and 5 years |
| SF-36 | Quality of Life SF-36 Questionnaire. Computer-based scoring services for the SF-36v2 are available through QualityMetric™ or its licensed certified vendors. | 1, 2, and 5 years |
| Biomarker profile in blood | Change in biomarkers in blood (APOE). As there exist no single ideal biomarker of AD this endpoint is partly exploratory. Biological material will be stored for future analysis in the search for new biomarkers. | 1, 2, and 5 years |
| Biomarker profile in cerebrospinal fluid | Change in biomarkers in cerebrospinal fluid (Amyloid Beta 1-42, Amyloid Beta 1-40, phosphor tau and total tau). As there exist no single ideal biomarker of AD this endpoint is partly exploratory. Biological material will be stored for future analysis in the search for new biomarkers. | 1, 2, and 5 years |
| Echocardiography - Cardiac dimensions - Left ventricular end diastolic diameter | Changes in cardiac dimensions - left ventricular end diastolic diameter (mm). | 1, 2, and 5 years |
| Echocardiography - Cardiac dimensions - Right ventricular dimension | Changes in cardiac dimensions - right ventricular dimension (mm). | 1, 2, and 5 years |
| Echocardiography - Cardiac volumes - Left ventricular and diastolic volume. | Changes in cardiac volumes - left ventricular and diastolic volume (mL). | 1, 2, and 5 years |
| Echocardiography - Cardiac volumes - Right ventricular volume | Changes in cardiac volumes. Right ventricular volume (mL). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Ejection fraction | Changes in functional indices - ejection fraction (%). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Left ventricular strain | Changes in functional indices - left ventricular strain (%). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Ventricular velocity | Changes in functional indices - ventricular velocity (cm/s). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Right ventricular strain | Changes in functional indices - right ventricular strain (%). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Left ventricular stiffness | Changes in functional indices - left ventricular stiffness. | 1, 2, and 5 years |
|
Exercise therapy, Blood transfusion, Plasma
|
Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercised plasma (ExPlas)<br>Dosage: 200 mL at every time point Dosage form: Solution for intravenous infusion Frequency of administration: 12 ExPlas transfusions during the time span of one year (weekly transfusions in 3 four-week periods) | Drug: ExPlas<br>* ExPlas (plasma from fit donors) is a Investigational Medicinal Product. ExPlas is plasma drawn by plasmapheresis once a month for 4 months, from a total of 30 donors (aged 18-40, BMI ≤27 kg/m2 and VO2max >50 mL/kg/min) at the Blood Bank at St. Olavs Hospital. All unites will be virus inactivated by the Intercept method (Cerus corporation, US) in accordance with the procedures at Blood Bank at St. Olavs Hospital.~The transfusion volume will be 200 mL at every time point.~The main study consists of 6 rounds of examinations in addition to 12 plasma transfusions during the time span of one year (weekly transfusions in 3 four-week periods) and one round of examinations 2 years after baseline. A follow-up visit is also planned 5 years after baseline.<br>|
| Active Comparator: Octaplasma<br>Dosage: 200 mL at every time point Dosage form: Solution for intravenous infusion Frequency of administration: 12 Octaplasma transfusions during the time span of one year (weekly transfusions in 3 four-week periods) | Drug: Octaplasma<br>* Octaplasma is defined as a Investigational Medicinal Product. Octaplasma is human pooled plasma produced by Octapharma (Lachen, Switzerland). The transfusion volume will be 200 mL at every time point .~The main study consists of 6 rounds of examinations in addition to 12 plasma transfusions during the time span of one year (weekly transfusions in 3 four-week periods) and one round of examinations 2 years after baseline. A follow-up visit is also planned 5 years after baseline.<br>|
| Placebo Comparator: Saline<br>Dosage: 200 mL at every time point Dosage form: Solution for intravenous infusion Frequency of administration: 12 saline infusions during the time span of one year (weekly transfusions in 3 four-week periods) | Drug: Saline<br>* Saline is provided by the hospital pharmacies in Central Norway. The infusion volume will be 200 mL at every time point.~The main study consists of 6 rounds of examinations in addition to 12 saline infusions during the time span of one year (weekly transfusions in 3 four-week periods) and one round of examinations 2 years after baseline. A follow-up visit is also planned 5 years after baseline.<br>|
|
Safety and Efficacy of Plasma Transfusion From Exercise-trained Donors in Patients With Early Alzheimer's Disease
Study Overview
=================
Brief Summary
-----------------
Introduction Given that exercise training reduces the risk of developing Alzheimer's disease (AD), induces changes in the blood composition and has widespread systemic benefits, it is reasonable to hypothesize that exercised plasma may have rejuvenative properties. The main objective is to test safety and tolerability of transfusing exercised plasma (ExPlas) from young, healthy, fit adults to patients with early AD. The study is a pilot for a future efficacy study. The key secondary objectives are examining the effect of plasma transfusions on cognitive function, fitness level, vascular risk profile, assessment of cerebral blood flow and hippocampal volume, quality of life, functional connectivity assessed by resting state functional MRI and biomarkers in blood and cerebrospinal fluid. Methods and analysis ExPlas is a double-blinded, randomized controlled clinical single center trial. Patients aged 50-75 years with diagnosis mild cognitive impairment or early AD will be recruited from two Norwegian hospitals. ExPlas is plasma drawn by plasmapheresis once a month for 4 months, from a total of 30 donors (aged 18-40, BMI ≤27 kg/m2 and VO2max >50 mL/kg/min). All units will be virus inactivated by the Intercept method in accordance with procedures at St. Olavs Hospital. Comparison with isotonic saline allows differentiation from a non-blood product. The main study consists of 6 rounds of examinations in addition to 12 plasma transfusions divided over three 4-weeks periods during study year-1. Follow-up examinations after 2 and 5 years after baseline is also planned. Ethics and dissemination Written informed consent will be obtained from all participants and participation is voluntary. All participants have a next of kin who will follow them throughout the study and represent the patient's interest. The study is approved by the Regional Committee for Medical and Health Research Ethics (REK 2018/702) and the Norwegian Medicines Agency (EudraCT No. 2018-000148-24).
Official Title
-----------------
Safety and Efficacy of Plasma Transfusion From Exercise-trained Donors in Patients With Early Alzheimer's Disease: The ExPlas Study
Conditions
-----------------
Alzheimer Disease
Intervention / Treatment
-----------------
* Drug: ExPlas
* Drug: Octaplasma
* Drug: Saline
Participation Criteria
=================
Eligibility Criteria
-----------------
Patient inclusion criteria: Diagnosis AD in early phase according to the IWG-2 criteria. Mini-Mental State Examination (MMSE) Score ≥20. In-vivo evidence of Alzheimer´s pathology (one of the following): Decreased Aβ42 together with increased t-tau or p-tau in CSF. Increased tracer retention on amyloid PET. Availability of a next of kin who knows the patient well and is willing to accompany the subject to all trial visits and give information about the patients functional level. Signed informed consent. The patient is judged fitted for the study and capable to cooperate in treatment and follow-up. Ability to communicate in Norwegian or another Scandinavian language. Patient exclusion criteria: Pregnancy or unwilling to use adequate birth control for the duration of and 6 months beyond study participation. Defined according to Clinical Trial Facilitation Group document Recommendations related to contraception and pregnancy testing in clinical trials. Positive for Hepatitis B, Hepatitis C or HIV at screening. Not qualified to give consent at inclusion. Any other condition judged to interfere with the safety of the patient or the intent and conduct of the study. Related to medical history: Stroke Anaphylaxis Prior adverse reaction to any human blood product Any history of a blood coagulation disorder or hypercoagulability Congestive heart failure, defined as any previous heart failure hospitalization, or current symptomatic heart failure in New York heart Association class ≥II with reduced, mid-range or preserved ejection fraction. Coagulation defect or hypercoagulopathy Uncontrolled hypertension Renal failure Prior intolerance to intravenous fluids Recent history of uncontrolled atrial fibrillation Bone marrow transplant IgA deficiency Severe protein S deficiency Thrombocytopenia (platelets < 40 x 10 to the power of 9/L) Contraindication for Octaplasma Related to medications or other treatments: Any concurrent use of anticoagulant therapy, clopidogrel or acetylsalicylic acid/Dipyridamol in combination. Initiation or change in the dosage of a acetylcholine esterase inhibitor (AChEI) or memantine during the trial (week 0-52). Participants will be urged to start on AChEI when diagnosis is communicated, and must be on a stable dose for at least one month prior to screening. Concurrent participation in another treatment trial for AD. If there was prior participation, the last dose of the investigational agent must have been given at least 6 months prior to screening, except if the patient received placebo medication. Treatment with any human blood product, including intravenous immunoglobulin, during the 6 months prior to screening or during the trial. Concurrent daily treatment with benzodiazepines, typical or atypical antipsychotics, long-acting opioids, or other medications that is judged to interfere with cognition. Intermittent treatment with short-acting benzodiazepines or atypical antipsychotics may be permitted, provided that no dose is administered within 72 hours prior to cognitive assessment. Related to magnetic resonance imaging: Claustrophobia Any metallic surgical implant, like a pacemaker or clip that is incompatible with MRI. Certain metallic implants like joint replacements may be permitted, provided that specific manufacturer specifications are available, and that the device is known to be safe for 7T MRI. In case a patient is not eligible for the 7T scanner, the 3T scanner will be used.
Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blinded, randomized controlled clinical phase II trial
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercised plasma (ExPlas)<br>Dosage: 200 mL at every time point Dosage form: Solution for intravenous infusion Frequency of administration: 12 ExPlas transfusions during the time span of one year (weekly transfusions in 3 four-week periods) | Drug: ExPlas<br>* ExPlas (plasma from fit donors) is a Investigational Medicinal Product. ExPlas is plasma drawn by plasmapheresis once a month for 4 months, from a total of 30 donors (aged 18-40, BMI ≤27 kg/m2 and VO2max >50 mL/kg/min) at the Blood Bank at St. Olavs Hospital. All unites will be virus inactivated by the Intercept method (Cerus corporation, US) in accordance with the procedures at Blood Bank at St. Olavs Hospital. The transfusion volume will be 200 mL at every time point. The main study consists of 6 rounds of examinations in addition to 12 plasma transfusions during the time span of one year (weekly transfusions in 3 four-week periods) and one round of examinations 2 years after baseline. A follow-up visit is also planned 5 years after baseline.<br>|
| Active Comparator: Octaplasma<br>Dosage: 200 mL at every time point Dosage form: Solution for intravenous infusion Frequency of administration: 12 Octaplasma transfusions during the time span of one year (weekly transfusions in 3 four-week periods) | Drug: Octaplasma<br>* Octaplasma is defined as a Investigational Medicinal Product. Octaplasma is human pooled plasma produced by Octapharma (Lachen, Switzerland). The transfusion volume will be 200 mL at every time point . The main study consists of 6 rounds of examinations in addition to 12 plasma transfusions during the time span of one year (weekly transfusions in 3 four-week periods) and one round of examinations 2 years after baseline. A follow-up visit is also planned 5 years after baseline.<br>|
| Placebo Comparator: Saline<br>Dosage: 200 mL at every time point Dosage form: Solution for intravenous infusion Frequency of administration: 12 saline infusions during the time span of one year (weekly transfusions in 3 four-week periods) | Drug: Saline<br>* Saline is provided by the hospital pharmacies in Central Norway. The infusion volume will be 200 mL at every time point. The main study consists of 6 rounds of examinations in addition to 12 saline infusions during the time span of one year (weekly transfusions in 3 four-week periods) and one round of examinations 2 years after baseline. A follow-up visit is also planned 5 years after baseline.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events | as a measure for safety and tolerability of the treatment | 1 year |
| Number of subjects who comply with the research protocol | as a measure for feasibility | 1 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CERAD-test | Change in performance in the CERAD (The Consortium to Establish a Registry for Alzheimer's Disease) Ten word Test. CERAD Word List consists of three test parts; immediate recall, delayed recall and recognition. The scoring range for immediate recall is 0-30, for delayed recall 0-10 and for recognition 0-20. Higher scores indicate better learning performance, memory performance and recognition performance. | 1, 2 and 5 years |
| MMSE | Change in the Mini-Mental State Examination Score. An MMSE score of ≥20 is criteria for inclusion. Higher scores >28 indicate normal cognitive function. Scores in the middle range 25-27 may indicate cognitive impairment. Lower scores <24 indicate cognitive impairment. | 1, 2, and 5 years |
| Trail-Making test A and B | Change in performance in Trail-Making test A and B. The Trail Making Tests are scored by how long it takes to complete the tests. Norms for completion time variate with age and educational level. Longer completion time indicates impaired visual attention, processing speed and executive function. | 1, 2, and 5 years |
| Clock Drawing Test | Change in scores in the Clock Drawing Test. The Clock Drawing Test has a scoring range 0-5. Higher scores indicate normal cognitive function. Lower scores <4 may indicate cognitive impairment, spatial dysfunction or neglect. | 1, 2, and 5 years |
| Controlled Oral Word Association Test (COWAT)-FAS | Change in scores in Controlled Oral Word Association Test (COWAT)-FAS. Scoring is based on how many words the person produces within 1 minute. The minimum score is 0, and there is no maximum score. Higher scores indicate better verbal fluency. Scoring norms are based on the persons age and education level. | 1, 2, and 5 years |
| Visual Object and Space Perception (VOSP) Silhouettes | Change in scores in Visual Object and Space Perception (VOSP) Silhouettes. Visual Object and Space Perception (VOSP) Silhouettes has a scoring range 0-30. Higher scores > 20 indicate normal visuospatial function, and lower scores < 20 indicate visuospatial dysfunction. | 1, 2, and 5 years |
| Clinical Dementia Rating Scale Global score and Sum of Boxes | Change in Clinical Dementia Rating Scale Global score and Sum of Boxes. Clinical Dementia Rating Scale (CDR) is a clinical scale for the staging of dementia. The Global Score ranges dementia severity from 0-3. The Sum of Boxes ranges dementia severity from 0-18. Higher scores indicate more severe disease. | 1, 2, and 5 years |
| The Lawton Instrumental Activities of Daily Living Scale (IADL) | Change in The Lawton Instrumental Activities of Daily Living Scale (IADL). The Lawton Instrumental Activities of Daily Living Scale (IADL) evaluates the person's ability to perform complex everyday activities. The score ranges from 8-31. Higher scores indicate lower functional level. | 1, 2, and 5 years |
| 6 minutes' walk test | Change in 6 minutes' walk-test | 1, 2, and 5 years |
| Functional MRI | Change in/Reduced hippocampal atrophy and preservation of functional connectivity assessed by resting state functional MRI. A secondary aim is to identify any effect of treatment group on MRI markers of both neurodegenerative and cerebrovascular disease. | 1, 2, and 5 years |
| SF-36 | Quality of Life SF-36 Questionnaire. Computer-based scoring services for the SF-36v2 are available through QualityMetric™ or its licensed certified vendors. | 1, 2, and 5 years |
| Biomarker profile in blood | Change in biomarkers in blood (APOE). As there exist no single ideal biomarker of AD this endpoint is partly exploratory. Biological material will be stored for future analysis in the search for new biomarkers. | 1, 2, and 5 years |
| Biomarker profile in cerebrospinal fluid | Change in biomarkers in cerebrospinal fluid (Amyloid Beta 1-42, Amyloid Beta 1-40, phosphor tau and total tau). As there exist no single ideal biomarker of AD this endpoint is partly exploratory. Biological material will be stored for future analysis in the search for new biomarkers. | 1, 2, and 5 years |
| Echocardiography - Cardiac dimensions - Left ventricular end diastolic diameter | Changes in cardiac dimensions - left ventricular end diastolic diameter (mm). | 1, 2, and 5 years |
| Echocardiography - Cardiac dimensions - Right ventricular dimension | Changes in cardiac dimensions - right ventricular dimension (mm). | 1, 2, and 5 years |
| Echocardiography - Cardiac volumes - Left ventricular and diastolic volume. | Changes in cardiac volumes - left ventricular and diastolic volume (mL). | 1, 2, and 5 years |
| Echocardiography - Cardiac volumes - Right ventricular volume | Changes in cardiac volumes. Right ventricular volume (mL). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Ejection fraction | Changes in functional indices - ejection fraction (%). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Left ventricular strain | Changes in functional indices - left ventricular strain (%). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Ventricular velocity | Changes in functional indices - ventricular velocity (cm/s). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Right ventricular strain | Changes in functional indices - right ventricular strain (%). | 1, 2, and 5 years |
| Echocardiography - Functional indices - Left ventricular stiffness | Changes in functional indices - left ventricular stiffness. | 1, 2, and 5 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Exercise therapy, Blood transfusion, Plasma
|
|
NCT03644329
|
Effect of Resistance Training Variable Manipulation in Postmenopausal Breast Cancer Survivors.
|
This study intends to evaluate the impact of resistance training variable manipulation (intensity and volume) on body composition, fatigability and functional capacity in postmenopausal breast cancer survivors.
|
The treatment for breast cancer (chemotherapy, radiotherapy and hormone therapy) provokes collateral effects,such as muscle mass and strength losses, increase of fat mass, fatigue and disability and reduced quality of life in postmenopausal breast cancer survivors. The resistance training is assumed as a non-pharmacologic interventions in postmenopausal breast cancer survivors. However, it is unclear whether the manipulation of training variables (intensity and volume) maximize the effects of resistance training on body composition, fatigability and functional capacity in postmenopausal breast cancer survivors.
|
Effect of Resistance Training Variable Manipulation (Intensity and Volume) on Body Composition, Fatigability and Functional Capacity in Postmenopausal Breast Cancer Survivors.
|
Breast Cancer Survivors, Postmenopause
|
* Other: Control group
* Other: Lower-load resistance training (LL)
* Other: Higher-load resistance training (HL)
* Other: Higher-volume resistance training (HV)
|
Inclusion Criteria:~Postmenopausal breast cancer survivors;~No supervised or unsupervised exercise at least for six months prior to the study.~Exclusion Criteria:~Alcoholics;~No controlled blood pressure and glucose;~Presence of myopathies, arthropathies, and neuropathies;~Presence of muscle, thromboembolic and gastrointestinal disorders, infection diseases.
|
50 Years
| null |
Female
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation the Fatigability | The fatigability will be evaluate by 60 maximum voluntary isometric contractions (3 s contraction, 2 s rest) in knee extensors at 70 degree | pre and post intervention (i.e. 12 weeks) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Four- meter walk test | The volunteers will walk 4 meter. The time will be computed to determine the gait velocity (m/s). | pre and post intervention (i.e. 12 weeks) |
| Fat mass | The fat mass (kg) will be assessed via dual-energy x-ray absorptiometry scanning (iDXA; GE Healthcare-Luna, Madison, WI; software Encore version 14.10). | pre intervention and post intervention (i.e. 12 weeks) |
| Muscle strength | Muscle strength will be evaluated by one repetition maximum (1RM) test. | pre and post intervention (i.e. 12 weeks) |
| Six Minutes-walk test (6MWT) | The volunteers will walk 6 minutes. The distance (meters) will be recorded after completes the test. The 6MWT will be performed indoor, on a flat floor in a sports court. | pre and post intervention (i.e. 12 weeks) |
| Timed Up and Go test | The volunteers will be advised to get up from a chair, walk three meters, turn around, go back to the chair, and sit down. The time (seconds) will be recorded. The test will be performed indoor, on a flat floor in a sports court. | pre and post intervention (i.e. 12 weeks) |
| Five-times-sit-to-stand test | The volunteers will rise from a chair and returned to the seated position as quickly as possible for five repetitions. The time will be recorded (seconds). | pre and post intervention (i.e. 12 weeks) |
| Muscle mass | The muscle mass (kg) will be assessed via dual-energy x-ray absorptiometry scanning (iDXA; GE Healthcare-Luna, Madison, WI; software Encore version 14.10). | pre and post intervention (i.e. 12 weeks) |
| 10-meter walk test | The volunteers will walk 10 meters. The gait speed will be evaluated (m/s). The test will be performed indoor, on a flat floor in a sports court. | pre and post intervention (i.e. 12 weeks) |
| 400-meter walk test | The volunteers will walk 400 meters. The gait speed will be evaluated (m/s). The test will be performed indoor, on a flat floor in a sports court. | pre and post intervention (i.e. 12 weeks) |
| 900-meter walk test | The volunteers will walk 900 meters. The gait speed will be evaluate (m/s). The test will be performed indoor, on a flat floor in a sports court. | pre and post intervention (i.e. 12 weeks) |
|
Breast Cancer Survivors, resistance Training, fatigability, Body Composition, Functional capacity
|
Neoplasms, Breast Diseases, Skin Diseases, Breast Neoplasms, Neoplasms by Site
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control group, CT<br>In the CT, the postmenopausal breast cancer survivers does not perform exercise. | Other: Control group<br>* The volunteers will not performed the interventions.<br>|
| Experimental: Lower-load resistance training (LL)<br>In the LL, the postmenopausal breast cancer survivers will be submitted to 12 weeks of resistance training with low loads ( i.e. three sets with 30% of one-repetition maximum). | Other: Lower-load resistance training (LL)<br>* The volunteers will be perform the resistance training, three times a week for 12 weeks on non-consecutive days, three sets with 30% of 1RM and repetition until or close to failure in each set and 1.5-min of rest between sets and exercises.<br>|
| Experimental: Higher-load resistance training (HL)<br>In the HL, the postmenopausal breast cancer survivers will be submitted to 12 weeks of resistance training with high loads (i.e. three sets with 80% of one maximum repetition). | Other: Higher-load resistance training (HL)<br>* The volunteers will be perform the resistance training, three times a week for 12 weeks on non-consecutive days, three sets with 80% of 1RM and repetition until or close to failure in each set and 1.5-min of rest between sets and exercises.<br>|
| Experimental: Higher-volume resistance training (HV)<br>In the HV, the postmenopause breast cancer survivers will be submitted to 12 weeks of resistance training with high volume ( i.e. six sets with 80% one maximum repetition). | Other: Higher-volume resistance training (HV)<br>* The volunteers will be perform the resistance training, three times a week for 12 weeks on non-consecutive days, six sets with 80% of 1RM and repetition until or close to failure in each set and 1.5-min of rest between sets and exercises.<br>|
|
Effect of Resistance Training Variable Manipulation in Postmenopausal Breast Cancer Survivors.
Study Overview
=================
Brief Summary
-----------------
This study intends to evaluate the impact of resistance training variable manipulation (intensity and volume) on body composition, fatigability and functional capacity in postmenopausal breast cancer survivors.
Detailed Description
-----------------
The treatment for breast cancer (chemotherapy, radiotherapy and hormone therapy) provokes collateral effects,such as muscle mass and strength losses, increase of fat mass, fatigue and disability and reduced quality of life in postmenopausal breast cancer survivors. The resistance training is assumed as a non-pharmacologic interventions in postmenopausal breast cancer survivors. However, it is unclear whether the manipulation of training variables (intensity and volume) maximize the effects of resistance training on body composition, fatigability and functional capacity in postmenopausal breast cancer survivors.
Official Title
-----------------
Effect of Resistance Training Variable Manipulation (Intensity and Volume) on Body Composition, Fatigability and Functional Capacity in Postmenopausal Breast Cancer Survivors.
Conditions
-----------------
Breast Cancer Survivors, Postmenopause
Intervention / Treatment
-----------------
* Other: Control group
* Other: Lower-load resistance training (LL)
* Other: Higher-load resistance training (HL)
* Other: Higher-volume resistance training (HV)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Postmenopausal breast cancer survivors; No supervised or unsupervised exercise at least for six months prior to the study. Exclusion Criteria: Alcoholics; No controlled blood pressure and glucose; Presence of myopathies, arthropathies, and neuropathies; Presence of muscle, thromboembolic and gastrointestinal disorders, infection diseases.
Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control group, CT<br>In the CT, the postmenopausal breast cancer survivers does not perform exercise. | Other: Control group<br>* The volunteers will not performed the interventions.<br>|
| Experimental: Lower-load resistance training (LL)<br>In the LL, the postmenopausal breast cancer survivers will be submitted to 12 weeks of resistance training with low loads ( i.e. three sets with 30% of one-repetition maximum). | Other: Lower-load resistance training (LL)<br>* The volunteers will be perform the resistance training, three times a week for 12 weeks on non-consecutive days, three sets with 30% of 1RM and repetition until or close to failure in each set and 1.5-min of rest between sets and exercises.<br>|
| Experimental: Higher-load resistance training (HL)<br>In the HL, the postmenopausal breast cancer survivers will be submitted to 12 weeks of resistance training with high loads (i.e. three sets with 80% of one maximum repetition). | Other: Higher-load resistance training (HL)<br>* The volunteers will be perform the resistance training, three times a week for 12 weeks on non-consecutive days, three sets with 80% of 1RM and repetition until or close to failure in each set and 1.5-min of rest between sets and exercises.<br>|
| Experimental: Higher-volume resistance training (HV)<br>In the HV, the postmenopause breast cancer survivers will be submitted to 12 weeks of resistance training with high volume ( i.e. six sets with 80% one maximum repetition). | Other: Higher-volume resistance training (HV)<br>* The volunteers will be perform the resistance training, three times a week for 12 weeks on non-consecutive days, six sets with 80% of 1RM and repetition until or close to failure in each set and 1.5-min of rest between sets and exercises.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation the Fatigability | The fatigability will be evaluate by 60 maximum voluntary isometric contractions (3 s contraction, 2 s rest) in knee extensors at 70 degree | pre and post intervention (i.e. 12 weeks) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Four- meter walk test | The volunteers will walk 4 meter. The time will be computed to determine the gait velocity (m/s). | pre and post intervention (i.e. 12 weeks) |
| Fat mass | The fat mass (kg) will be assessed via dual-energy x-ray absorptiometry scanning (iDXA; GE Healthcare-Luna, Madison, WI; software Encore version 14.10). | pre intervention and post intervention (i.e. 12 weeks) |
| Muscle strength | Muscle strength will be evaluated by one repetition maximum (1RM) test. | pre and post intervention (i.e. 12 weeks) |
| Six Minutes-walk test (6MWT) | The volunteers will walk 6 minutes. The distance (meters) will be recorded after completes the test. The 6MWT will be performed indoor, on a flat floor in a sports court. | pre and post intervention (i.e. 12 weeks) |
| Timed Up and Go test | The volunteers will be advised to get up from a chair, walk three meters, turn around, go back to the chair, and sit down. The time (seconds) will be recorded. The test will be performed indoor, on a flat floor in a sports court. | pre and post intervention (i.e. 12 weeks) |
| Five-times-sit-to-stand test | The volunteers will rise from a chair and returned to the seated position as quickly as possible for five repetitions. The time will be recorded (seconds). | pre and post intervention (i.e. 12 weeks) |
| Muscle mass | The muscle mass (kg) will be assessed via dual-energy x-ray absorptiometry scanning (iDXA; GE Healthcare-Luna, Madison, WI; software Encore version 14.10). | pre and post intervention (i.e. 12 weeks) |
| 10-meter walk test | The volunteers will walk 10 meters. The gait speed will be evaluated (m/s). The test will be performed indoor, on a flat floor in a sports court. | pre and post intervention (i.e. 12 weeks) |
| 400-meter walk test | The volunteers will walk 400 meters. The gait speed will be evaluated (m/s). The test will be performed indoor, on a flat floor in a sports court. | pre and post intervention (i.e. 12 weeks) |
| 900-meter walk test | The volunteers will walk 900 meters. The gait speed will be evaluate (m/s). The test will be performed indoor, on a flat floor in a sports court. | pre and post intervention (i.e. 12 weeks) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast Cancer Survivors, resistance Training, fatigability, Body Composition, Functional capacity
|
NCT04532151
|
Optical Coherence Tomography Imaging in Systemic Sclerosis
|
Systemic sclerosis (SSc) is an autoimmune disorder characterized by early vascular endothelial involvement. SSc is a rare and devastating multi-visceral disease when fibrotic lesions extend to the skin and other tissues (heart, lungs, kidneys). The severity of skin involvement in SSc is correlated with functional prognosis and survival. To date, there is no validated tool for a reliable quantitative assessment of skin fibrosis.~Optical coherence tomography (OCT) is an innovative non-invasive skin imaging technique that allows micrometric analysis of the superficial layers of the skin. Previous study showed that OCT could detect the loss of the dermal-epidermal junction in an objective and non-invasive way, which is correlated with severity of skin fibrosis.~The aim of OCTISS study is to evaluate the skin involvement of patients with early SSc using OCT imaging. This will be early diagnosis of fibrosis lesions and help identify patients at an early stage.
|
Systemic sclerosis (SSc) is a rare autoimmune disorder. It is characterized by fibrosis and vascular obliteration in the skin and other organs. Skin damage, manifested by thickening of the skin tissue, is often one of the first signs of the disease. Pathogenesis is dominated by early microvascular changes targeting endothelial cells and with the release of several mediators promoting an inflammatory response and vascular remodeling. This inflammatory cascade results in fibrosis lesions. Early diagnosis of fibrosing skin lesions is essential in SSc since their severity is correlated with functional prognosis and survival. To date, there is no validated tool to reliably quantify skin fibrosis. The semi-quantitative Modified Rodnan score (mRSS), based on clinical assessment of skin thickening at 17 anatomical areas, is widely used. The main limitation of this method is its inter-operator variability. The histopathological analysis of the skin biopsy is interesting but invasive. The new non-invasive and reproducible tools are needed to evaluate skin fibrosis for early diagnosis of SSc.~Optical coherence tomography (OCT) is an innovative imaging technique that uses a light wave to capture 3D images of a material that scatters light. OCT allows real-time, direct and high-resolution imaging of the morphology of the biological sample (such as skin) without ionizing radiation. In SSc, the cutaneous fibrosis is characterized by a deregulated production of the components of the extracellular matrix, in particular collagen. Previous results showed that the dermal-epidermal junction could be observed in healthy subjects using OCT. In patients with SSc and skin involvement, the visualization of this junction could be reduced. The results suggest a possible correlation between the intensity of visualization of the dermo-epidermal junction and the severity of cutaneous fibrosis.~In this project, we would like to compare the skin involvement of the dorsal surface of a finger between patients with early SSc and control subjects using non-invasive OCT imaging. The study population meets the criteria for early SCS, with onset of disease less than 2 years and without clinically detectable skin involvement. In a second time, other imaging techniques (HD ultrasound) or fluid silicone molding technique will be used to evaluate the progression of skin fibrosis or the morphological characteristics of the skin or vascular network of the patient with early SSc. To complete the work, these parameters will be evaluated in other anatomical sites (outer and inner side of the forearm) or in another group of patients (Established SSc patients with clinical cutaneous sclerosis) or at another timepoint (M24). The hypothesis of this study is that OCT can be used to identify SSc patients at a stage where the lesions are still early and reversible.~This is a prospective, monocentric, comparative, open-label and longitudinal patient study with duration of 36 months. The duration of the inclusion period will be 12 months. The participation of each subject is from 1 hour (for group 2 and 3) to 24 months (for group 1). We planned to include 60 patients in the Department of Rheumatology of the University Hospital of Strasbourg (20 patients from each group).~The different measures in the study are not invasive. No specific biological sampling of the study will be conducted. There will be no change for the treatment of patients either.
|
Optical Coherence Tomography Imaging in Systemic Sclerosis
|
Systemic Sclerosis, Early Systemic Sclerosis Without Clinical Scleroderma and Onset < 2 Years
|
* Diagnostic Test: Non-invasive skin imaging assessment
|
IInclusion criteria~Major subject (age ≥ 18 years)~Male or female subject~Subject affiliated to a social health insurance scheme~Subject having signed an informed consent~Subject having been informed of the results of the prior medical examination~Inclusion criteria specific to each group~Group 1 Early SSc group: Patients with SSc according to ACR / EULAR criteria (2013) early onset <2 years and without clinical cutaneous sclerosis~Group 2 Established SSc group: Patients with SSc according to ACR / EULAR criteria (2013) with cutaneous sclerosis~Group 3 Control group: Hospitalized patients in the Rheumatology Department of the University Hospitals of Strasbourg, excluding connective tissue disease~Exclusion criteria:~Non-inclusion criteria for patients / controls in 3 groups~Subject having undergone a physical treatment (radiotherapy, surgical intervention ...) on the cutaneous sites studied~Subjects who received general corticosteroid therapy in the last 3 months~Subjects being treated with topical corticosteroids on the different cutaneous sites studied~Impossibility to give clear information of subject (subject in emergency situation, subject with difficulties of understanding ...)~Subject in exclusion period (determined by previous or current study),~Subject under the protection of justice, guardianship or curatorship~Pregnancy (on declaration of the patient)~Non-inclusion criteria specific to each group~- Group 1 Early SSc group: Patients with SSc and having a clinical cutaneous sclerosis~- Group 2 Established SSc group: Patients with criteria for another systemic autoimmune disease~- Group 3 Control group:~Subjects with scleroderma,~Subjects with Raynaud's phenomenon~Subjects with other sclerosing disease (morphea, Shulman,…)~Diabetic subjects
|
18 Years
| null |
All
|
No
|
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optic density of the papillo-reticular dermis on the dorsal surface of a finger | The optic density of the papillo-reticular dermis, 300 μm deep, on the dorsal surface of a finger will be measured in all three groups using optical coherence tomography (OCT) | This parameter will be evaluated during a hospital consultation. The test lasts 30 minutes. For all three groups, the measurements will be taken at the time of the inclusion visit (V0) |
| Optic density of the papillo-reticular dermis on the dorsal surface of a finger | | Only the patient of group 1 (Early SSc group) will be evaluated again during the visit of Month 24 (V M24). |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optic density of the papillo-reticular dermis at the outer and inner side of the forearm | The optic density of the papillo-reticular dermis, 300 μm deep, at the outer and inner side of the forearm will be measured in all three patient groups using OCT. | These parameters will be evaluated during a hospital consultation. The test lasts 30 minutes. For all three groups, the measurements will be taken at the time of the inclusion visit (V0). |
| Optic density of the papillo-reticular dermis at the outer and inner side of the forearm | The optic density of the papillo-reticular dermis, 300 μm deep, at the outer and inner side of the forearm will be measured in all three patient groups using OCT. | Only the patient of group 1 (Early SSc group) will be evaluated again during the visit of Month 24 (V M24). |
| Modified Rodnan skin score (mRSS) | The Modified Rodnan Score (mRSS) will be evaluated by an experienced clinician at each anatomical site studied during a hospital consultation. The test lasts 5 minutes. The evaluator will be blinded from the results of the imaging. | The assessment will be applied only to patients in group 1 (Early SSc group) and group 2 (Established SSc group) at the inclusion visit (V0). |
| Modified Rodnan skin score (mRSS) | | Only the patient of group 1 (Early SSc group) will be evaluated again during the visit of Month 24 (V M24). |
| The thickness of the hypodermis, obtained by HD ultrasound. | | Day 0 |
| The thickness of the dermis, obtained by HD ultrasound | | Day 0 |
| The distribution of tension forces exerted within the dermis by fluid silicone molding techniques | | Day 0 |
| The optic density of the papillo-reticular dermis, 300 μm deep, at the outer and inner side of the forearm will be measured in all three patient groups using OCT. | | Day 0 |
|
Scleroderma, Optical coherence tomography (OCT), Systemic sclerosis
|
Scleroderma, Systemic, Scleroderma, Diffuse, Sclerosis, Pathologic Processes, Connective Tissue Diseases, Skin Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Early SSc group<br>Patients with SSc according to the criteria ACR / EULAR 2013, without scleroderma Normal routine clinical examinations and routine biology tests will be performed. For non-invasive imaging specific to the study, various parameters will be measured on the finger and forearm by LC-OCT, LC-OCT-Doppler, HD ultrasound as well as fluid silicone molding in a dimly lit room. The mRSS will be evaluated by an experienced clinician, blinded from imaging measurements.~Patients will be reassessed at M24. The participation of each subject will be 24 months, with two visits of one hour.~The clinical data corresponding to the current practice will be collected in a study specific case report form. | Diagnostic Test: Non-invasive skin imaging assessment<br>* Intervention Description : (Limit: 1000 characters) Do not repeat information already included in arm/group descriptions. Specify details not covered in associated Arm~One session of Non-invasive skin imaging assessment contained:~an examination on LC-OCT~an examination on LC-OCT-doppler~a fluid silicone molding~an examination on HD ultrasound~The measurements will be applied on 3 skin sites: the dorsal surface of the finger, the inner face and the outer surface of the forearm.~The imaging assessment lasts 30 minutes in a dimly lit room where the humidity and temperature are stable.<br>|
| Other: Established SSc group<br>Patients with SSc according to criteria ACR / EULAR 2013 with scleroderma Normal routine clinical examinations and routine biology tests will be performed. For non-invasive imaging specific to the study, various parameters will be measured on the finger and forearm by LC-OCT, LC-OCT-Doppler, HD ultrasound as well as fluid silicone molding in a dimly lit room. The mRSS will be evaluated by an experienced clinician, blinded from imaging measurements. The participation of each subject will be one hour.~The clinical data corresponding to the current practice will be collected in a study specific case report form. | Diagnostic Test: Non-invasive skin imaging assessment<br>* Intervention Description : (Limit: 1000 characters) Do not repeat information already included in arm/group descriptions. Specify details not covered in associated Arm~One session of Non-invasive skin imaging assessment contained:~an examination on LC-OCT~an examination on LC-OCT-doppler~a fluid silicone molding~an examination on HD ultrasound~The measurements will be applied on 3 skin sites: the dorsal surface of the finger, the inner face and the outer surface of the forearm.~The imaging assessment lasts 30 minutes in a dimly lit room where the humidity and temperature are stable.<br>|
| Other: Control group:<br>Patient without systemic sclerosis Normal routine clinical examinations and routine biology tests will be performed. For non-invasive imaging specific to the study, various parameters will be measured on the finger and forearm by LC-OCT, LC-OCT-Doppler, HD ultrasound as well as fluid silicone molding in a dimly lit room. The participation of each subject will be one hour.~The clinical data corresponding to the current practice will be collected in a study specific case report form. | Diagnostic Test: Non-invasive skin imaging assessment<br>* Intervention Description : (Limit: 1000 characters) Do not repeat information already included in arm/group descriptions. Specify details not covered in associated Arm~One session of Non-invasive skin imaging assessment contained:~an examination on LC-OCT~an examination on LC-OCT-doppler~a fluid silicone molding~an examination on HD ultrasound~The measurements will be applied on 3 skin sites: the dorsal surface of the finger, the inner face and the outer surface of the forearm.~The imaging assessment lasts 30 minutes in a dimly lit room where the humidity and temperature are stable.<br>|
|
Optical Coherence Tomography Imaging in Systemic Sclerosis
Study Overview
=================
Brief Summary
-----------------
Systemic sclerosis (SSc) is an autoimmune disorder characterized by early vascular endothelial involvement. SSc is a rare and devastating multi-visceral disease when fibrotic lesions extend to the skin and other tissues (heart, lungs, kidneys). The severity of skin involvement in SSc is correlated with functional prognosis and survival. To date, there is no validated tool for a reliable quantitative assessment of skin fibrosis. Optical coherence tomography (OCT) is an innovative non-invasive skin imaging technique that allows micrometric analysis of the superficial layers of the skin. Previous study showed that OCT could detect the loss of the dermal-epidermal junction in an objective and non-invasive way, which is correlated with severity of skin fibrosis. The aim of OCTISS study is to evaluate the skin involvement of patients with early SSc using OCT imaging. This will be early diagnosis of fibrosis lesions and help identify patients at an early stage.
Detailed Description
-----------------
Systemic sclerosis (SSc) is a rare autoimmune disorder. It is characterized by fibrosis and vascular obliteration in the skin and other organs. Skin damage, manifested by thickening of the skin tissue, is often one of the first signs of the disease. Pathogenesis is dominated by early microvascular changes targeting endothelial cells and with the release of several mediators promoting an inflammatory response and vascular remodeling. This inflammatory cascade results in fibrosis lesions. Early diagnosis of fibrosing skin lesions is essential in SSc since their severity is correlated with functional prognosis and survival. To date, there is no validated tool to reliably quantify skin fibrosis. The semi-quantitative Modified Rodnan score (mRSS), based on clinical assessment of skin thickening at 17 anatomical areas, is widely used. The main limitation of this method is its inter-operator variability. The histopathological analysis of the skin biopsy is interesting but invasive. The new non-invasive and reproducible tools are needed to evaluate skin fibrosis for early diagnosis of SSc. Optical coherence tomography (OCT) is an innovative imaging technique that uses a light wave to capture 3D images of a material that scatters light. OCT allows real-time, direct and high-resolution imaging of the morphology of the biological sample (such as skin) without ionizing radiation. In SSc, the cutaneous fibrosis is characterized by a deregulated production of the components of the extracellular matrix, in particular collagen. Previous results showed that the dermal-epidermal junction could be observed in healthy subjects using OCT. In patients with SSc and skin involvement, the visualization of this junction could be reduced. The results suggest a possible correlation between the intensity of visualization of the dermo-epidermal junction and the severity of cutaneous fibrosis. In this project, we would like to compare the skin involvement of the dorsal surface of a finger between patients with early SSc and control subjects using non-invasive OCT imaging. The study population meets the criteria for early SCS, with onset of disease less than 2 years and without clinically detectable skin involvement. In a second time, other imaging techniques (HD ultrasound) or fluid silicone molding technique will be used to evaluate the progression of skin fibrosis or the morphological characteristics of the skin or vascular network of the patient with early SSc. To complete the work, these parameters will be evaluated in other anatomical sites (outer and inner side of the forearm) or in another group of patients (Established SSc patients with clinical cutaneous sclerosis) or at another timepoint (M24). The hypothesis of this study is that OCT can be used to identify SSc patients at a stage where the lesions are still early and reversible. This is a prospective, monocentric, comparative, open-label and longitudinal patient study with duration of 36 months. The duration of the inclusion period will be 12 months. The participation of each subject is from 1 hour (for group 2 and 3) to 24 months (for group 1). We planned to include 60 patients in the Department of Rheumatology of the University Hospital of Strasbourg (20 patients from each group). The different measures in the study are not invasive. No specific biological sampling of the study will be conducted. There will be no change for the treatment of patients either.
Official Title
-----------------
Optical Coherence Tomography Imaging in Systemic Sclerosis
Conditions
-----------------
Systemic Sclerosis, Early Systemic Sclerosis Without Clinical Scleroderma and Onset < 2 Years
Intervention / Treatment
-----------------
* Diagnostic Test: Non-invasive skin imaging assessment
Participation Criteria
=================
Eligibility Criteria
-----------------
IInclusion criteria Major subject (age ≥ 18 years) Male or female subject Subject affiliated to a social health insurance scheme Subject having signed an informed consent Subject having been informed of the results of the prior medical examination Inclusion criteria specific to each group Group 1 Early SSc group: Patients with SSc according to ACR / EULAR criteria (2013) early onset <2 years and without clinical cutaneous sclerosis Group 2 Established SSc group: Patients with SSc according to ACR / EULAR criteria (2013) with cutaneous sclerosis Group 3 Control group: Hospitalized patients in the Rheumatology Department of the University Hospitals of Strasbourg, excluding connective tissue disease Exclusion criteria: Non-inclusion criteria for patients / controls in 3 groups Subject having undergone a physical treatment (radiotherapy, surgical intervention ...) on the cutaneous sites studied Subjects who received general corticosteroid therapy in the last 3 months Subjects being treated with topical corticosteroids on the different cutaneous sites studied Impossibility to give clear information of subject (subject in emergency situation, subject with difficulties of understanding ...) Subject in exclusion period (determined by previous or current study), Subject under the protection of justice, guardianship or curatorship Pregnancy (on declaration of the patient) Non-inclusion criteria specific to each group - Group 1 Early SSc group: Patients with SSc and having a clinical cutaneous sclerosis - Group 2 Established SSc group: Patients with criteria for another systemic autoimmune disease - Group 3 Control group: Subjects with scleroderma, Subjects with Raynaud's phenomenon Subjects with other sclerosing disease (morphea, Shulman,…) Diabetic subjects
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Early SSc group<br>Patients with SSc according to the criteria ACR / EULAR 2013, without scleroderma Normal routine clinical examinations and routine biology tests will be performed. For non-invasive imaging specific to the study, various parameters will be measured on the finger and forearm by LC-OCT, LC-OCT-Doppler, HD ultrasound as well as fluid silicone molding in a dimly lit room. The mRSS will be evaluated by an experienced clinician, blinded from imaging measurements. Patients will be reassessed at M24. The participation of each subject will be 24 months, with two visits of one hour. The clinical data corresponding to the current practice will be collected in a study specific case report form. | Diagnostic Test: Non-invasive skin imaging assessment<br>* Intervention Description : (Limit: 1000 characters) Do not repeat information already included in arm/group descriptions. Specify details not covered in associated Arm One session of Non-invasive skin imaging assessment contained: an examination on LC-OCT an examination on LC-OCT-doppler a fluid silicone molding an examination on HD ultrasound The measurements will be applied on 3 skin sites: the dorsal surface of the finger, the inner face and the outer surface of the forearm. The imaging assessment lasts 30 minutes in a dimly lit room where the humidity and temperature are stable.<br>|
| Other: Established SSc group<br>Patients with SSc according to criteria ACR / EULAR 2013 with scleroderma Normal routine clinical examinations and routine biology tests will be performed. For non-invasive imaging specific to the study, various parameters will be measured on the finger and forearm by LC-OCT, LC-OCT-Doppler, HD ultrasound as well as fluid silicone molding in a dimly lit room. The mRSS will be evaluated by an experienced clinician, blinded from imaging measurements. The participation of each subject will be one hour. The clinical data corresponding to the current practice will be collected in a study specific case report form. | Diagnostic Test: Non-invasive skin imaging assessment<br>* Intervention Description : (Limit: 1000 characters) Do not repeat information already included in arm/group descriptions. Specify details not covered in associated Arm One session of Non-invasive skin imaging assessment contained: an examination on LC-OCT an examination on LC-OCT-doppler a fluid silicone molding an examination on HD ultrasound The measurements will be applied on 3 skin sites: the dorsal surface of the finger, the inner face and the outer surface of the forearm. The imaging assessment lasts 30 minutes in a dimly lit room where the humidity and temperature are stable.<br>|
| Other: Control group:<br>Patient without systemic sclerosis Normal routine clinical examinations and routine biology tests will be performed. For non-invasive imaging specific to the study, various parameters will be measured on the finger and forearm by LC-OCT, LC-OCT-Doppler, HD ultrasound as well as fluid silicone molding in a dimly lit room. The participation of each subject will be one hour. The clinical data corresponding to the current practice will be collected in a study specific case report form. | Diagnostic Test: Non-invasive skin imaging assessment<br>* Intervention Description : (Limit: 1000 characters) Do not repeat information already included in arm/group descriptions. Specify details not covered in associated Arm One session of Non-invasive skin imaging assessment contained: an examination on LC-OCT an examination on LC-OCT-doppler a fluid silicone molding an examination on HD ultrasound The measurements will be applied on 3 skin sites: the dorsal surface of the finger, the inner face and the outer surface of the forearm. The imaging assessment lasts 30 minutes in a dimly lit room where the humidity and temperature are stable.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optic density of the papillo-reticular dermis on the dorsal surface of a finger | The optic density of the papillo-reticular dermis, 300 μm deep, on the dorsal surface of a finger will be measured in all three groups using optical coherence tomography (OCT) | This parameter will be evaluated during a hospital consultation. The test lasts 30 minutes. For all three groups, the measurements will be taken at the time of the inclusion visit (V0) |
| Optic density of the papillo-reticular dermis on the dorsal surface of a finger | | Only the patient of group 1 (Early SSc group) will be evaluated again during the visit of Month 24 (V M24). |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optic density of the papillo-reticular dermis at the outer and inner side of the forearm | The optic density of the papillo-reticular dermis, 300 μm deep, at the outer and inner side of the forearm will be measured in all three patient groups using OCT. | These parameters will be evaluated during a hospital consultation. The test lasts 30 minutes. For all three groups, the measurements will be taken at the time of the inclusion visit (V0). |
| Optic density of the papillo-reticular dermis at the outer and inner side of the forearm | The optic density of the papillo-reticular dermis, 300 μm deep, at the outer and inner side of the forearm will be measured in all three patient groups using OCT. | Only the patient of group 1 (Early SSc group) will be evaluated again during the visit of Month 24 (V M24). |
| Modified Rodnan skin score (mRSS) | The Modified Rodnan Score (mRSS) will be evaluated by an experienced clinician at each anatomical site studied during a hospital consultation. The test lasts 5 minutes. The evaluator will be blinded from the results of the imaging. | The assessment will be applied only to patients in group 1 (Early SSc group) and group 2 (Established SSc group) at the inclusion visit (V0). |
| Modified Rodnan skin score (mRSS) | | Only the patient of group 1 (Early SSc group) will be evaluated again during the visit of Month 24 (V M24). |
| The thickness of the hypodermis, obtained by HD ultrasound. | | Day 0 |
| The thickness of the dermis, obtained by HD ultrasound | | Day 0 |
| The distribution of tension forces exerted within the dermis by fluid silicone molding techniques | | Day 0 |
| The optic density of the papillo-reticular dermis, 300 μm deep, at the outer and inner side of the forearm will be measured in all three patient groups using OCT. | | Day 0 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Scleroderma, Optical coherence tomography (OCT), Systemic sclerosis
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.