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NCT04381273
|
Oral Health and Psychosocial Factors During the Covid-19 Pandemic
|
This prospective observational study examines the effects of the Covid-19 pandemic on oral health, taking psychosocial factors into account, and the possible impact of a high periodontitis risk on the severity of the need for treatment in Covid-19 patients.
|
Oral Health and Psychosocial Factors During the Covid-19 Pandemic
|
Covid-19, Periodontal Diseases, COVID
|
* Other: No intervention
|
Inclusion Criteria:~≥18 years old~Residence in Germany~Understanding of study participation and consent~Exclusion Criteria:~<18 years old~Residence outside of Germany
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| How do people assess their oral health-related quality of life in times of the Covid-19 pandemic? | The survey consists of validated and unvalidated items giving the opportunity to assess periodontitis risk, psychosocial stress, anxiety, depression and oral health related quality of life as well as questions focusing on experiences of the covid-19 pandemic. | 08.05.2020-31.07.2020 |
| Does the periodontitis risk have an influence on the severety of the Covid-19 disease and its' treatment? | The survey consists of validated and unvalidated items giving the opportunity to assess periodontitis risk, psychosocial stress, anxiety, depression and oral health related quality of life as well as questions focusing on experiences of the covid-19 pandemic. | 08.05.2020-31.07.2020 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Do psychosocial stress factors in times of the Covid-19 pandemic have an impact on their oral health related quality of life? | The survey consists of validated and unvalidated items giving the opportunity to assess periodontitis risk, psychosocial stress, anxiety, depression and oral health related quality of life as well as questions focusing on experiences of the covid-19 pandemic. | 08.05.2020-31.07.2020 |
| Have people changed their oral hygiene practices in times of the Covid-19 pandemic? | The survey consists of validated and unvalidated items giving the opportunity to assess periodontitis risk, psychosocial stress, anxiety, depression and oral health related quality of life as well as questions focusing on experiences of the covid-19 pandemic. | 08.05.2020-31.07.2020 |
|
COVID-19, Periodontal Diseases, Pneumonia, Viral, Pneumonia, Respiratory Tract Infections, Infections, Virus Diseases, Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Lung Diseases, Respiratory Tract Diseases, Mouth Diseases, Stomatognathic Diseases
|
| Intervention/Treatment |
| --- |
|Other: No intervention|questionnaire-based assessment|
|
Oral Health and Psychosocial Factors During the Covid-19 Pandemic
Study Overview
=================
Brief Summary
-----------------
This prospective observational study examines the effects of the Covid-19 pandemic on oral health, taking psychosocial factors into account, and the possible impact of a high periodontitis risk on the severity of the need for treatment in Covid-19 patients.
Official Title
-----------------
Oral Health and Psychosocial Factors During the Covid-19 Pandemic
Conditions
-----------------
Covid-19, Periodontal Diseases, COVID
Intervention / Treatment
-----------------
* Other: No intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥18 years old Residence in Germany Understanding of study participation and consent Exclusion Criteria: <18 years old Residence outside of Germany
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?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Other: No intervention|questionnaire-based assessment|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| How do people assess their oral health-related quality of life in times of the Covid-19 pandemic? | The survey consists of validated and unvalidated items giving the opportunity to assess periodontitis risk, psychosocial stress, anxiety, depression and oral health related quality of life as well as questions focusing on experiences of the covid-19 pandemic. | 08.05.2020-31.07.2020 |
| Does the periodontitis risk have an influence on the severety of the Covid-19 disease and its' treatment? | The survey consists of validated and unvalidated items giving the opportunity to assess periodontitis risk, psychosocial stress, anxiety, depression and oral health related quality of life as well as questions focusing on experiences of the covid-19 pandemic. | 08.05.2020-31.07.2020 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Do psychosocial stress factors in times of the Covid-19 pandemic have an impact on their oral health related quality of life? | The survey consists of validated and unvalidated items giving the opportunity to assess periodontitis risk, psychosocial stress, anxiety, depression and oral health related quality of life as well as questions focusing on experiences of the covid-19 pandemic. | 08.05.2020-31.07.2020 |
| Have people changed their oral hygiene practices in times of the Covid-19 pandemic? | The survey consists of validated and unvalidated items giving the opportunity to assess periodontitis risk, psychosocial stress, anxiety, depression and oral health related quality of life as well as questions focusing on experiences of the covid-19 pandemic. | 08.05.2020-31.07.2020 |
|
|||
NCT00475592
|
Validation of Esophageal Variceal Grading: A Comparative Study of Upper Gastrointestinal (GI) Endoscopy and Capsule Endoscopy
|
The purpose of this study is to develop a grading system for esophageal varices using capsule endoscopy in patients with portal hypertension and cirrhosis.
|
Up to 35% of patients with cirrhosis will develop esophageal varices, which carry with them a 1-year and 3-year bleeding rate of 33% and 41%, respectively. Screening for varices with a video endoscopy is limited by its cost, patient compliance, and the risks of sedating a patient with portal hypertension. Capsule endoscopy is a novel method that may reduce the costs and increase compliance for screening.~The investigators propose to screen 100 consecutive patients with advanced cirrhosis for esophageal varices. A capsule endoscopy and video endoscopy will be done on the same day. The varices seen on video endoscopy will be graded using a standard grading scale. Both capsule and video endoscopy images will be assessed in a blinded fashion by 4 independent investigators. Finally, the video endoscopic images will be compared to capsule endoscopy to develop a capsule endoscopy grading system that corresponds to video endoscopy.~The primary endpoint of the study will be to develop a grading system for esophageal varices using capsule endoscopy. Secondary endpoints of the study include sensitivity, specificity, inter- and intraobserver variation of variceal grading using capsule endoscopy; patient acceptance as assessed on a visual analogue scale; and a cost comparison (facility fees + professional fees) of the two screening methods.
|
Validation of Esophageal Variceal Grading: A Comparative Study of Upper Gastrointestinal (GI) Endoscopy and Capsule Endoscopy
|
Esophageal and Gastric Varices
|
* Device: Esophageal Capsule Endoscopy
* Device: Upper Gastrointestinal Endoscopy
|
Inclusion Criteria:~Advanced cirrhosis with portal hypertension based on imaging, clinical suspicion, or liver biopsy~Age greater than or equal to 18 years old~Able to give consent~Exclusion Criteria:~Current implantable cardioverter-defibrillators or pacemaker in place~Suspected intestinal obstruction~Esophageal swallowing disorder~Esophageal stenosis~Age less than 18 years old~Pregnancy~Known Zenker's diverticulum~Patients with previous endoscopic or surgical esophageal treatment
|
18 Years
| null |
All
|
No
|
Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of the study will be to develop a grading system for esophageal varices using capsule endoscopy. | | Two years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoints include sensitivity, specificity, inter- and intraobserver variation of variceal grading using capsule endoscopy; patient acceptance; and a cost comparison (facility + professional fees) of the two screening methods. | | Two years |
|
Esophageal Varices, Gastric Varices, Capsule Endoscopy, Portal Hypertension, Cirrhosis, Gastrointestinal Hemorrhage
|
Esophageal and Gastric Varices, Esophageal Diseases, Gastrointestinal Diseases, Digestive System Diseases, Hypertension, Portal, Liver Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capsule Endoscopy<br> | Device: Esophageal Capsule Endoscopy<br> <br> |
| Active Comparator: Upper Gastrointestinal Endoscopy<br> | Device: Upper Gastrointestinal Endoscopy<br> <br> |
|
Validation of Esophageal Variceal Grading: A Comparative Study of Upper Gastrointestinal (GI) Endoscopy and Capsule Endoscopy
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to develop a grading system for esophageal varices using capsule endoscopy in patients with portal hypertension and cirrhosis.
Detailed Description
-----------------
Up to 35% of patients with cirrhosis will develop esophageal varices, which carry with them a 1-year and 3-year bleeding rate of 33% and 41%, respectively. Screening for varices with a video endoscopy is limited by its cost, patient compliance, and the risks of sedating a patient with portal hypertension. Capsule endoscopy is a novel method that may reduce the costs and increase compliance for screening. The investigators propose to screen 100 consecutive patients with advanced cirrhosis for esophageal varices. A capsule endoscopy and video endoscopy will be done on the same day. The varices seen on video endoscopy will be graded using a standard grading scale. Both capsule and video endoscopy images will be assessed in a blinded fashion by 4 independent investigators. Finally, the video endoscopic images will be compared to capsule endoscopy to develop a capsule endoscopy grading system that corresponds to video endoscopy. The primary endpoint of the study will be to develop a grading system for esophageal varices using capsule endoscopy. Secondary endpoints of the study include sensitivity, specificity, inter- and intraobserver variation of variceal grading using capsule endoscopy; patient acceptance as assessed on a visual analogue scale; and a cost comparison (facility fees + professional fees) of the two screening methods.
Official Title
-----------------
Validation of Esophageal Variceal Grading: A Comparative Study of Upper Gastrointestinal (GI) Endoscopy and Capsule Endoscopy
Conditions
-----------------
Esophageal and Gastric Varices
Intervention / Treatment
-----------------
* Device: Esophageal Capsule Endoscopy
* Device: Upper Gastrointestinal Endoscopy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Advanced cirrhosis with portal hypertension based on imaging, clinical suspicion, or liver biopsy Age greater than or equal to 18 years old Able to give consent Exclusion Criteria: Current implantable cardioverter-defibrillators or pacemaker in place Suspected intestinal obstruction Esophageal swallowing disorder Esophageal stenosis Age less than 18 years old Pregnancy Known Zenker's diverticulum Patients with previous endoscopic or surgical esophageal treatment
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: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capsule Endoscopy<br> | Device: Esophageal Capsule Endoscopy<br> <br> |
| Active Comparator: Upper Gastrointestinal Endoscopy<br> | Device: Upper Gastrointestinal Endoscopy<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of the study will be to develop a grading system for esophageal varices using capsule endoscopy. | | Two years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoints include sensitivity, specificity, inter- and intraobserver variation of variceal grading using capsule endoscopy; patient acceptance; and a cost comparison (facility + professional fees) of the two screening methods. | | Two years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Esophageal Varices, Gastric Varices, Capsule Endoscopy, Portal Hypertension, Cirrhosis, Gastrointestinal Hemorrhage
|
NCT03979508
|
Abemaciclib in Treating Patients With Surgically Resectable, Chemotherapy Resistant, Triple Negative Breast Cancer
|
This phase II trial studies how well abemaciclib works in treating patients with triple negative breast cancer that can be removed by surgery (resectable) and does not respond to treatment with chemotherapy alone, or in combination with pembrolizumab. Abemaciclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
|
PRIMARY OBJECTIVE:~I. To examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy resistant triple negative breast cancer (TNBC) patients following neoadjuvant chemotherapy regimen without the addition of pembrolizumab (Cohort A).~II. To examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy resistant TNBC patients following a neoadjuvant chemotherapy regimen with the addition of pembrolizumab (Cohort B).~SECONDARY OBJECTIVES for Cohort A and Cohort B Independently:~I. Assess abemaciclib toxicities. II. To examine the effects of abemaciclib on the percentage of vimentin expressing invasive cancer cells~III. Within TNBC molecular subtypes (basal, mesenchymal, and luminal androgen receptor [LAR]), to evaluate the effects of abemaciclib on:~IIIa. The individual elements of tumor grade (mitoses, nuclear pleomorphism, and tubule formation).~IIIb. Tumor proliferation (as measured by tumor Ki-67 and serum tyrosine kinase inhibitor [TKI]).~IIIc. pDUB3 as well as epithelial-mesenchymal transition (EMT) markers including SNAIL/SLUG, TWIST, and E-Cadherin as measured by immunohistochemistry (IHC).~IIId. Quantification of tumor-infiltrating lymphocytes (as examined by hematoxylin and eosin [H&E]).~EXPLORATORY OBJECTIVES for Cohort A and Cohort B Independently:~I. To evaluate the effect of abemaciclib on tumor ribonucleic acid (RNA) expression.~II. To evaluate the effects of abemaciclib on the immune phenotype of peripheral blood mononuclear cells (PBMC), by evaluating expression of a panel of cell surface markers optimized of identification of human immune cell subpopulations.~III. To evaluate the effects of abemaciclib on tumor-infiltrating immune cells in formalin-fixed paraffin-embedded (FFPE) tumor sections, using multiplexed imaging technologies (e.g imaging mass cytometry, Nanostring digital spatial profiling [DSP] or CODEX) which will include:~IIIa. Genes directly involved in tumor cell antigen presentation (e.g. B2M, HLA-A, HLA-B, HLA-C, TAP1, TAP2, TAPBP).~IIIb. Interferon-stimulated genes (ISGs) that regulate antigen presentation (e.g. STAT1, NLRC5) and other ISGs (e.g. IRFs, OAS2).~IIIc. Genes involved in double-strand ribonucleic acid (dsRNA) response (e.g. DDX58, DHX58).~IIId. Genes encoding interferons, including type 3 IFNs (e.g. IFNL1, IFNL2, IFNL3).~IIIe. Genes indicating a cytotoxic T cell response (e.g. PRF1, GZMB). IIIf. Regulatory T-cell (Treg)-specific transcription factor genes (e.g. FOXP3, IKZF2).~IV. To assess the difference in the frequency of JAK-2 amplification among patients whose post-abemaciclib CD8/FOXP3 ratio >= 1.6 and that among patients whose post-abemaciclib CD8/FOXP3 ratio < 1.6.~V. To generate organoids for future research. VI. To evaluate changes in the microbiome with exposure to abemaciclib.~OUTLINE: Patients are assigned to 1 of 2 cohorts.~COHORT A: Patients receive a neoadjuvant chemotherapy regimen without pembrolizumab.~GROUP 1: Patients undergo standard of care surgical resection.~GROUP 2: Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy.~After completion of study treatment, patients in group 2 are followed up within 30-60 days.~COHORT B: Patients receive a neoadjuvant chemotherapy regimen in combination with pembrolizumab.~GROUP 3: Patients undergo standard of care surgical resection.~GROUP 4: Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy.~After completion of study treatment, patients in group 4 are followed up within 30-60 days.
|
Window Trial of Abemaciclib for Surgically Resectable, Chemotherapy-Resistant, Triple Negative Breast Cancer (a BEAUTY Study*)
|
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Breast Ductal Carcinoma In Situ, Breast Fibrocystic Change, Breast Lobular Carcinoma In Situ, Invasive Breast Carcinoma, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8, Triple-Negative Breast Carcinoma
|
* Drug: Abemaciclib
* Procedure: Therapeutic Conventional Surgery
|
Inclusion Criteria:~Women of age >=18 years~PRE-REGISTRATION: Clinical T1-4, N0-3, M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (AJCC) staging version 8.~Note: Benign breast disease, lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS) in the ipsilateral or contralateral breast is allowed.~Note: Additional ipsilateral or contralateral invasive breast cancer is allowed. The index lesion is the largest triple-negative, chemotherapy-resistant lesion.~PRE-REGISTRATION: Histological confirmation of triple negative invasive breast cancer (defined as estrogen receptor [ER] =< 10%, progesterone receptor [PR] =< 10% and HER2 not amplified by in situ hybridization [ISH] or immunohistochemistry [IHC] 0/1) at diagnosis.~PRE-REGISTRATION: Cohort A: CLOSED TO PRE-REGISTRATION and REGISTRATION as of protocol amendment 6 (04/14/2023) Neoadjuvant chemotherapy (NAC) with one of the following regimens that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:~Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC)~Note: Carboplatin may be added to these regimens~AC or EC or FEC followed by docetaxel or paclitaxel~Note: Carboplatin may be added to these regimens~Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)~Docetaxel in combination with cyclophosphamide (TC) (for patients who are not candidates for anthracyclines)~Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel) (for patients who are not candidates for anthracyclines)~PRE-REGISTRATION: Cohort B: Neoadjuvant chemotherapy (NAC) with one of the following regimens in combination with pembrolizumab that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:~Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) Note: Carboplatin may be added to these regimens~AC or EC or FEC followed by docetaxel or paclitaxel [Note: Carboplatin may be added to these regimens]~Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)~Docetaxel in combination with cyclophosphamide (TC)~Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel)~PRE-REGISTRATION: Residual lesion/enhancement seen in the breast on breast imaging performed after completion of NAC.~PRE-REGISTRATION: Able to swallow oral medication.~PRE-REGISTRATION: Willing to undergo biopsy for research.~PRE-REGISTRATION: Willing to provide tissue and blood samples for correlative research purposes.~PRE-REGISTRATION: Willing to stop use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =< 7 days prior to registration.~PRE-REGISTRATION: Provide written informed consent.~REGISTRATION: Registration must occur =< 56 days after last dose of NAC.~REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2.~REGISTRATION: COHORT B GROUP 4 ONLY: The following laboratory values obtained after completion of NAC but =< 14 days prior to registration:~REGISTRATION: COHORT B GROUP 4 ONLY: Absolute neutrophil count (ANC) >= 1500/mm^3.~REGISTRATION: COHORT B GROUP 4 ONLY: Platelets (PLT) >= 100,000/mm^3.~REGISTRATION: COHORT B GROUP 4 ONLY: Hemoglobin (HgB) >= 8.0 g/dL.~REGISTRATION: COHORT B GROUP 4 ONLY: Total bilirubin =< 1.5 x upper limit of normal (ULN).~REGISTRATION: COHORT B GROUP 4 ONLY: Aspartate transaminase (AST) serum glutamic oxaloacetic transaminase (SGOT) =< 3 x ULN.~REGISTRATION: COHORT B GROUP 4 ONLY: Alanine transaminase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN.~REGISTRATION: COHORT B GROUP 4 ONLY: Serum creatinine =< 1.5 x ULN.~REGISTRATION: GROUP 2 ONLY: Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only.~Exclusion Criteria:~PRE-REGISTRATION: History of deep venous thrombosis (DVT) or pulmonary embolisms (PE) =< 12 months prior to preregistration; OR Active DVT and/or PE requiring anti-coagulant therapy.~NOTE: Patients who are on anti-coagulant therapy for maintenance are eligible as long as the DVT and/or PE was > 12 months prior to enrollment and there is no evidence for active thrombosis (either DVT or PE).~NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.~PRE-REGISTRATION: Prior treatment with CDK 4/6 inhibitors (e.g. palbociclib, ribociclib, abemaciclib, etc.)~PRE-REGISTRATION: Prior treatment with radiation for this breast cancer.~PRE-REGISTRATION: Prior incisional or excisional breast biopsy for this cancer.~PRE-REGISTRATION: Any contraindications to pre-registration biopsy (such as bleeding diatheses, etc.).~PRE-REGISTRATION: Receiving any investigational agent which would be considered as a treatment for the primary neoplasm.~PRE-REGISTRATION: Other active malignancy =< 3 years prior to registration.~EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.~NOTE: If there is a history of prior malignancy, they must not be receiving another specific treatment for prior malignancy.~PRE-REGISTRATION: Biopsy proven Stage IV breast cancer.~PRE-REGISTRATION: Serious pre-existing medical conditions that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g., estimated creatinine clearance < 30 ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).~PRE-REGISTRATION: History of any of the following conditions:~Syncope of cardiovascular etiology.~Ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation).~Sudden cardiac arrest.~NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.~REGISTRATION: COHORT B GROUP 4: Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:~Pregnant persons.~Nursing persons.~Persons of childbearing potential who are unwilling to employ adequate contraception.~REGISTRATION: COHORT B GROUP 4: Failure to recover to grade 1 or lower from effects of neoadjuvant chemotherapy.~Exceptions: Residual alopecia and grade 2 peripheral neuropathy are allowed.~REGISTRATION: COHORT B GROUP 4: Concurrent use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =< 7 days prior to registration.~REGISTRATION: COHORT B GROUP 4: Known infections as follows (NOTE: Screening is not required for enrollment):~Active systemic bacterial infection requiring intravenous antibiotics.~Active fungal infection (requiring intravenous or oral antifungal treatment).~Detectable viral infections (e.g. known human immunodeficiency virus [HIV], known active hepatitis B or C).~REGISTRATION: COHORT B GROUP 4: Concurrent use of chemotherapy, radiotherapy, immunotherapy, or other components of neoadjuvant treatment.~NOTE: Patients must complete all elements of NAC ≥21 days prior to starting abemaciclib.
|
18 Years
| null |
Female
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who have a CD8/FOXP3 ratio < 1.6 in their residual tumors after neoadjuvant chemotherapy (NAC) that convert to CD8/FOXP3 ratio >= 1.6 | A Simon optimum two stage phase II clinical trial design was chosen to test the null hypothesis that the rate of conversion to post-abemaciclib CD8/FOXP3 ratio of 1.6 or more is =< 5% against the alternative that rate of conversion to post-abemaciclib CD8/FOXP3 ratio of 1.6 or more is >= 20% with the target probability of a type I error and probability of a type II error set to 0.10. The probability of terminating after the first stage is 0.736, if the null hypothesis is true. A 90% confidence interval for this rate of conversion will be constructed using the Duffy-Santner approach taking into account the sequential nature of the study | Up to 21 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Adverse events will be monitored and graded with attribution assigned using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For each type of adverse event (AE) reported, the proportion of patients experiencing a grade 2 or worse level of that AE will be determined. | Up to 60 days |
| Changes in vimentin expression | Vimentin expression will be evaluated by immunohistochemistry (IHC) with using 0, 1+, 2+ or 3+ scoring scheme. A point estimate of the proportion of eligible patients whose post-NAC residual tumor Vimentin expression levels were 2+ or 3+ and then fell to 0 or 1+ after abemaciclib among the eligible patients whose began abemaciclib treatment after a post NAC residual tumor Vimentin expression level finding of 2+ or 3+ will be calculated. A 90% confidence interval for this proportion will be constructed using one-sample binomial confidence for proportions. | Up to 60 days |
| Impact of length of treatment | Association between amount of abemaciclib received and the change in CD8/FOXP3 ratio after abemaciclib will be explored graphically. A plot of the change in change in CD8/FOXP3 ratio after abemaciclib and days of treatment will be constructed to visually assess for trends. Also, the a 90% confidence interval for the difference in binomial proportions will be constructed to assess whether the proportion of patients whose post abemaciclib CD8/FOXP3 ratio >= 1.6 after completing 14-21 days of abemaciclib differs between those who discontinued abemaciclib the day prior to surgery and who discontinued abemaciclib 2 or more days prior to surgery. A 90% binomial confidence interval for the proportion of women who failed to complete 14-21 days of abemaciclib or underwent surgery or breast biopsy 2 or more days after last dose of abemaciclib among the eligible women who began abemaciclib treatment. | Up to 60 days |
|
Neoplasms, Carcinoma, Breast Neoplasms, Triple Negative Breast Neoplasms, Carcinoma in Situ, Carcinoma, Ductal, Carcinoma, Intraductal, Noninfiltrating, Carcinoma, Lobular, Breast Carcinoma In Situ, Carcinoma, Ductal, Breast, Fibrocystic Breast Disease, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms by Site, Breast Diseases, Skin Diseases, Adenocarcinoma, Neoplasms, Ductal, Lobular, and Medullary
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A Group 1; Cohort B Group 3 (surgery)<br>Patients undergo standard of care surgical resection. | Procedure: Therapeutic Conventional Surgery<br>* Undergo standard of care surgical resection<br>|
| Experimental: Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery)<br>Patients receive abemaciclib PO BID on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy. | Drug: Abemaciclib<br>* Given PO<br>* Other names: Verzenio;Procedure: Therapeutic Conventional Surgery<br>* Undergo standard of care surgical resection<br>|
|
Abemaciclib in Treating Patients With Surgically Resectable, Chemotherapy Resistant, Triple Negative Breast Cancer
Study Overview
=================
Brief Summary
-----------------
This phase II trial studies how well abemaciclib works in treating patients with triple negative breast cancer that can be removed by surgery (resectable) and does not respond to treatment with chemotherapy alone, or in combination with pembrolizumab. Abemaciclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description
-----------------
PRIMARY OBJECTIVE: I. To examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy resistant triple negative breast cancer (TNBC) patients following neoadjuvant chemotherapy regimen without the addition of pembrolizumab (Cohort A). II. To examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy resistant TNBC patients following a neoadjuvant chemotherapy regimen with the addition of pembrolizumab (Cohort B). SECONDARY OBJECTIVES for Cohort A and Cohort B Independently: I. Assess abemaciclib toxicities. II. To examine the effects of abemaciclib on the percentage of vimentin expressing invasive cancer cells III. Within TNBC molecular subtypes (basal, mesenchymal, and luminal androgen receptor [LAR]), to evaluate the effects of abemaciclib on: IIIa. The individual elements of tumor grade (mitoses, nuclear pleomorphism, and tubule formation). IIIb. Tumor proliferation (as measured by tumor Ki-67 and serum tyrosine kinase inhibitor [TKI]). IIIc. pDUB3 as well as epithelial-mesenchymal transition (EMT) markers including SNAIL/SLUG, TWIST, and E-Cadherin as measured by immunohistochemistry (IHC). IIId. Quantification of tumor-infiltrating lymphocytes (as examined by hematoxylin and eosin [H&E]). EXPLORATORY OBJECTIVES for Cohort A and Cohort B Independently: I. To evaluate the effect of abemaciclib on tumor ribonucleic acid (RNA) expression. II. To evaluate the effects of abemaciclib on the immune phenotype of peripheral blood mononuclear cells (PBMC), by evaluating expression of a panel of cell surface markers optimized of identification of human immune cell subpopulations. III. To evaluate the effects of abemaciclib on tumor-infiltrating immune cells in formalin-fixed paraffin-embedded (FFPE) tumor sections, using multiplexed imaging technologies (e.g imaging mass cytometry, Nanostring digital spatial profiling [DSP] or CODEX) which will include: IIIa. Genes directly involved in tumor cell antigen presentation (e.g. B2M, HLA-A, HLA-B, HLA-C, TAP1, TAP2, TAPBP). IIIb. Interferon-stimulated genes (ISGs) that regulate antigen presentation (e.g. STAT1, NLRC5) and other ISGs (e.g. IRFs, OAS2). IIIc. Genes involved in double-strand ribonucleic acid (dsRNA) response (e.g. DDX58, DHX58). IIId. Genes encoding interferons, including type 3 IFNs (e.g. IFNL1, IFNL2, IFNL3). IIIe. Genes indicating a cytotoxic T cell response (e.g. PRF1, GZMB). IIIf. Regulatory T-cell (Treg)-specific transcription factor genes (e.g. FOXP3, IKZF2). IV. To assess the difference in the frequency of JAK-2 amplification among patients whose post-abemaciclib CD8/FOXP3 ratio >= 1.6 and that among patients whose post-abemaciclib CD8/FOXP3 ratio < 1.6. V. To generate organoids for future research. VI. To evaluate changes in the microbiome with exposure to abemaciclib. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT A: Patients receive a neoadjuvant chemotherapy regimen without pembrolizumab. GROUP 1: Patients undergo standard of care surgical resection. GROUP 2: Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy. After completion of study treatment, patients in group 2 are followed up within 30-60 days. COHORT B: Patients receive a neoadjuvant chemotherapy regimen in combination with pembrolizumab. GROUP 3: Patients undergo standard of care surgical resection. GROUP 4: Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy. After completion of study treatment, patients in group 4 are followed up within 30-60 days.
Official Title
-----------------
Window Trial of Abemaciclib for Surgically Resectable, Chemotherapy-Resistant, Triple Negative Breast Cancer (a BEAUTY Study*)
Conditions
-----------------
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Breast Ductal Carcinoma In Situ, Breast Fibrocystic Change, Breast Lobular Carcinoma In Situ, Invasive Breast Carcinoma, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8, Triple-Negative Breast Carcinoma
Intervention / Treatment
-----------------
* Drug: Abemaciclib
* Procedure: Therapeutic Conventional Surgery
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women of age >=18 years PRE-REGISTRATION: Clinical T1-4, N0-3, M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (AJCC) staging version 8. Note: Benign breast disease, lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS) in the ipsilateral or contralateral breast is allowed. Note: Additional ipsilateral or contralateral invasive breast cancer is allowed. The index lesion is the largest triple-negative, chemotherapy-resistant lesion. PRE-REGISTRATION: Histological confirmation of triple negative invasive breast cancer (defined as estrogen receptor [ER] =< 10%, progesterone receptor [PR] =< 10% and HER2 not amplified by in situ hybridization [ISH] or immunohistochemistry [IHC] 0/1) at diagnosis. PRE-REGISTRATION: Cohort A: CLOSED TO PRE-REGISTRATION and REGISTRATION as of protocol amendment 6 (04/14/2023) Neoadjuvant chemotherapy (NAC) with one of the following regimens that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request: Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) Note: Carboplatin may be added to these regimens AC or EC or FEC followed by docetaxel or paclitaxel Note: Carboplatin may be added to these regimens Docetaxel in combination with doxorubicin and cyclophosphamide (TAC) Docetaxel in combination with cyclophosphamide (TC) (for patients who are not candidates for anthracyclines) Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel) (for patients who are not candidates for anthracyclines) PRE-REGISTRATION: Cohort B: Neoadjuvant chemotherapy (NAC) with one of the following regimens in combination with pembrolizumab that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request: Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) Note: Carboplatin may be added to these regimens AC or EC or FEC followed by docetaxel or paclitaxel [Note: Carboplatin may be added to these regimens] Docetaxel in combination with doxorubicin and cyclophosphamide (TAC) Docetaxel in combination with cyclophosphamide (TC) Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel) PRE-REGISTRATION: Residual lesion/enhancement seen in the breast on breast imaging performed after completion of NAC. PRE-REGISTRATION: Able to swallow oral medication. PRE-REGISTRATION: Willing to undergo biopsy for research. PRE-REGISTRATION: Willing to provide tissue and blood samples for correlative research purposes. PRE-REGISTRATION: Willing to stop use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =< 7 days prior to registration. PRE-REGISTRATION: Provide written informed consent. REGISTRATION: Registration must occur =< 56 days after last dose of NAC. REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2. REGISTRATION: COHORT B GROUP 4 ONLY: The following laboratory values obtained after completion of NAC but =< 14 days prior to registration: REGISTRATION: COHORT B GROUP 4 ONLY: Absolute neutrophil count (ANC) >= 1500/mm^3. REGISTRATION: COHORT B GROUP 4 ONLY: Platelets (PLT) >= 100,000/mm^3. REGISTRATION: COHORT B GROUP 4 ONLY: Hemoglobin (HgB) >= 8.0 g/dL. REGISTRATION: COHORT B GROUP 4 ONLY: Total bilirubin =< 1.5 x upper limit of normal (ULN). REGISTRATION: COHORT B GROUP 4 ONLY: Aspartate transaminase (AST) serum glutamic oxaloacetic transaminase (SGOT) =< 3 x ULN. REGISTRATION: COHORT B GROUP 4 ONLY: Alanine transaminase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN. REGISTRATION: COHORT B GROUP 4 ONLY: Serum creatinine =< 1.5 x ULN. REGISTRATION: GROUP 2 ONLY: Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only. Exclusion Criteria: PRE-REGISTRATION: History of deep venous thrombosis (DVT) or pulmonary embolisms (PE) =< 12 months prior to preregistration; OR Active DVT and/or PE requiring anti-coagulant therapy. NOTE: Patients who are on anti-coagulant therapy for maintenance are eligible as long as the DVT and/or PE was > 12 months prior to enrollment and there is no evidence for active thrombosis (either DVT or PE). NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care. PRE-REGISTRATION: Prior treatment with CDK 4/6 inhibitors (e.g. palbociclib, ribociclib, abemaciclib, etc.) PRE-REGISTRATION: Prior treatment with radiation for this breast cancer. PRE-REGISTRATION: Prior incisional or excisional breast biopsy for this cancer. PRE-REGISTRATION: Any contraindications to pre-registration biopsy (such as bleeding diatheses, etc.). PRE-REGISTRATION: Receiving any investigational agent which would be considered as a treatment for the primary neoplasm. PRE-REGISTRATION: Other active malignancy =< 3 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history of prior malignancy, they must not be receiving another specific treatment for prior malignancy. PRE-REGISTRATION: Biopsy proven Stage IV breast cancer. PRE-REGISTRATION: Serious pre-existing medical conditions that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g., estimated creatinine clearance < 30 ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea). PRE-REGISTRATION: History of any of the following conditions: Syncope of cardiovascular etiology. Ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation). Sudden cardiac arrest. NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care. REGISTRATION: COHORT B GROUP 4: Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: Pregnant persons. Nursing persons. Persons of childbearing potential who are unwilling to employ adequate contraception. REGISTRATION: COHORT B GROUP 4: Failure to recover to grade 1 or lower from effects of neoadjuvant chemotherapy. Exceptions: Residual alopecia and grade 2 peripheral neuropathy are allowed. REGISTRATION: COHORT B GROUP 4: Concurrent use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =< 7 days prior to registration. REGISTRATION: COHORT B GROUP 4: Known infections as follows (NOTE: Screening is not required for enrollment): Active systemic bacterial infection requiring intravenous antibiotics. Active fungal infection (requiring intravenous or oral antifungal treatment). Detectable viral infections (e.g. known human immunodeficiency virus [HIV], known active hepatitis B or C). REGISTRATION: COHORT B GROUP 4: Concurrent use of chemotherapy, radiotherapy, immunotherapy, or other components of neoadjuvant treatment. NOTE: Patients must complete all elements of NAC ≥21 days prior to starting abemaciclib.
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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A Group 1; Cohort B Group 3 (surgery)<br>Patients undergo standard of care surgical resection. | Procedure: Therapeutic Conventional Surgery<br>* Undergo standard of care surgical resection<br>|
| Experimental: Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery)<br>Patients receive abemaciclib PO BID on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy. | Drug: Abemaciclib<br>* Given PO<br>* Other names: Verzenio;Procedure: Therapeutic Conventional Surgery<br>* Undergo standard of care surgical resection<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who have a CD8/FOXP3 ratio < 1.6 in their residual tumors after neoadjuvant chemotherapy (NAC) that convert to CD8/FOXP3 ratio >= 1.6 | A Simon optimum two stage phase II clinical trial design was chosen to test the null hypothesis that the rate of conversion to post-abemaciclib CD8/FOXP3 ratio of 1.6 or more is =< 5% against the alternative that rate of conversion to post-abemaciclib CD8/FOXP3 ratio of 1.6 or more is >= 20% with the target probability of a type I error and probability of a type II error set to 0.10. The probability of terminating after the first stage is 0.736, if the null hypothesis is true. A 90% confidence interval for this rate of conversion will be constructed using the Duffy-Santner approach taking into account the sequential nature of the study | Up to 21 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Adverse events will be monitored and graded with attribution assigned using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. For each type of adverse event (AE) reported, the proportion of patients experiencing a grade 2 or worse level of that AE will be determined. | Up to 60 days |
| Changes in vimentin expression | Vimentin expression will be evaluated by immunohistochemistry (IHC) with using 0, 1+, 2+ or 3+ scoring scheme. A point estimate of the proportion of eligible patients whose post-NAC residual tumor Vimentin expression levels were 2+ or 3+ and then fell to 0 or 1+ after abemaciclib among the eligible patients whose began abemaciclib treatment after a post NAC residual tumor Vimentin expression level finding of 2+ or 3+ will be calculated. A 90% confidence interval for this proportion will be constructed using one-sample binomial confidence for proportions. | Up to 60 days |
| Impact of length of treatment | Association between amount of abemaciclib received and the change in CD8/FOXP3 ratio after abemaciclib will be explored graphically. A plot of the change in change in CD8/FOXP3 ratio after abemaciclib and days of treatment will be constructed to visually assess for trends. Also, the a 90% confidence interval for the difference in binomial proportions will be constructed to assess whether the proportion of patients whose post abemaciclib CD8/FOXP3 ratio >= 1.6 after completing 14-21 days of abemaciclib differs between those who discontinued abemaciclib the day prior to surgery and who discontinued abemaciclib 2 or more days prior to surgery. A 90% binomial confidence interval for the proportion of women who failed to complete 14-21 days of abemaciclib or underwent surgery or breast biopsy 2 or more days after last dose of abemaciclib among the eligible women who began abemaciclib treatment. | Up to 60 days |
|
|
NCT01231633
|
Comparison of Initial Ozurdex (Dexamethasone Implant) to Avastin (Bevacizumab) for Treatment of Macular Edema Caused by Central Retinal Vein Occlusion (CRVO)
|
The purpose of this study is to compare visual improvement and total number of intraocular injections in eyes with macular edema following central retinal vein occlusion (CRVO)after initial treatment with Ozurdex (dexamethasone implant) or Avastin (bevacizumab).
|
Comparative Study of Initial Ozurdex (Dexamethasone Implant) Versus Avastin (Bevacizumab) in the Treatment of Macular Edema Following Central Retinal Vein Occlusion (CRVO)
|
Macular Edema, Central Retinal Vein Occlusion
|
* Drug: Ozurdex
* Drug: Avastin
|
Inclusion Criteria:~Presence of central retinal vein occlusion (CRVO)~Age 18 years or older~ETDRS (Early Treatment Diabetic Retinopathy Study) Visual acuity between 3 and 72 letters and approximate Snellen equivalent of 20/40 to 20/800~OCT Central foveal thickness >250 microns~Negative pregnancy test for women of childbearing potential~Ability to provide written informed consent~Capable of complying with study protocol~Exclusion Criteria:~History of glaucoma in the study eye with intraocular pressure >21mmHg on more than one topical medication. Combination drugs are considered more than one medication~History of steroid-related glaucoma (steroid response)~Previous intraocular injection of steroid medication within 90 days~Avastin (bevacizumab) or Lucentis (ranibizumab) within 60 days~Evidence of significant retinal ischemia on fluorescein angiography in the opinion of the treating physician~Previous intraocular surgery (e.g. Cataract Surgery) with in 60 days~Concurrent ocular disease that would limit visual acuity in the opinion of the treating physician~Dense cataract that precludes clinical examination and retinal imaging of the retina~History of allergy to dexamethasone, bevacizumab, betadine~Ocular or systemic conditions that may pose a threat to the health of the subject in the opinion of the treating physician~Unwilling or unable to follow or comply with all study related procedures~Current participation in another clinical medical investigation or trial or has received any investigational drug within 12 weeks prior to enrollment
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Visual Acuity (Number of ETDRS Early Treatment Diabetic Retinopathy Study Letters), at Month 6 as Compared With Baseline in Each Treatment Arm | The change in visual acuity (number of ETDRS - Early Treatment Diabetic Retinopathy Study letters), at Month 6 as compared with baseline in each treatment arm | Baseline - Month 6 |
| The Total Number of Additional Avastin Injections Following Initial Treatment in Each Treatment Arm | Total Number of addiitonal Avastin injections during study- From baseline to Month 6 | Baseline - Month 6 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Central Mean Thickness Based on OCT | Change in Central Mean Thickness based on OCT from baseline to Month 6t | Baseline to 6 Months |
|
Macular Edema, Central Retinal Vein Occlusion
|
Dexamethasone, Bevacizumab, Antineoplastic Agents, Immunological, Antineoplastic Agents, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Growth Substances, Physiological Effects of Drugs, Growth Inhibitors, Anti-Inflammatory Agents, Antiemetics, Autonomic Agents, Peripheral Nervous System Agents, Gastrointestinal Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Antineoplastic Agents, Hormonal
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Subjects randomized to this arm will receive one initial treatment with Ozurdex then treated with Avastin if needed. | Drug: Ozurdex<br>* Ozurdex, 0.7mg dexamethasone<br>* Other names: Dexamethasone implant;Drug: Avastin<br>* Formulated as a 1.25mg/0.05ml sterile solution given by intravitreal injection monthly as needed.<br>* Other names: Avastin, bevacizumab;|
| Active Comparator: Group 2<br>Subjects randomized to this arm will receive one initial treatment with Avastin then treated with Avastin if needed. | Drug: Avastin<br>* Formulated as a 1.25mg/0.05ml sterile solution given by intravitreal injection monthly as needed.<br>* Other names: Avastin, bevacizumab;|
|
Comparison of Initial Ozurdex (Dexamethasone Implant) to Avastin (Bevacizumab) for Treatment of Macular Edema Caused by Central Retinal Vein Occlusion (CRVO)
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare visual improvement and total number of intraocular injections in eyes with macular edema following central retinal vein occlusion (CRVO)after initial treatment with Ozurdex (dexamethasone implant) or Avastin (bevacizumab).
Official Title
-----------------
Comparative Study of Initial Ozurdex (Dexamethasone Implant) Versus Avastin (Bevacizumab) in the Treatment of Macular Edema Following Central Retinal Vein Occlusion (CRVO)
Conditions
-----------------
Macular Edema, Central Retinal Vein Occlusion
Intervention / Treatment
-----------------
* Drug: Ozurdex
* Drug: Avastin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Presence of central retinal vein occlusion (CRVO) Age 18 years or older ETDRS (Early Treatment Diabetic Retinopathy Study) Visual acuity between 3 and 72 letters and approximate Snellen equivalent of 20/40 to 20/800 OCT Central foveal thickness >250 microns Negative pregnancy test for women of childbearing potential Ability to provide written informed consent Capable of complying with study protocol Exclusion Criteria: History of glaucoma in the study eye with intraocular pressure >21mmHg on more than one topical medication. Combination drugs are considered more than one medication History of steroid-related glaucoma (steroid response) Previous intraocular injection of steroid medication within 90 days Avastin (bevacizumab) or Lucentis (ranibizumab) within 60 days Evidence of significant retinal ischemia on fluorescein angiography in the opinion of the treating physician Previous intraocular surgery (e.g. Cataract Surgery) with in 60 days Concurrent ocular disease that would limit visual acuity in the opinion of the treating physician Dense cataract that precludes clinical examination and retinal imaging of the retina History of allergy to dexamethasone, bevacizumab, betadine Ocular or systemic conditions that may pose a threat to the health of the subject in the opinion of the treating physician Unwilling or unable to follow or comply with all study related procedures Current participation in another clinical medical investigation or trial or has received any investigational drug within 12 weeks prior to 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
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Subjects randomized to this arm will receive one initial treatment with Ozurdex then treated with Avastin if needed. | Drug: Ozurdex<br>* Ozurdex, 0.7mg dexamethasone<br>* Other names: Dexamethasone implant;Drug: Avastin<br>* Formulated as a 1.25mg/0.05ml sterile solution given by intravitreal injection monthly as needed.<br>* Other names: Avastin, bevacizumab;|
| Active Comparator: Group 2<br>Subjects randomized to this arm will receive one initial treatment with Avastin then treated with Avastin if needed. | Drug: Avastin<br>* Formulated as a 1.25mg/0.05ml sterile solution given by intravitreal injection monthly as needed.<br>* Other names: Avastin, bevacizumab;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Visual Acuity (Number of ETDRS Early Treatment Diabetic Retinopathy Study Letters), at Month 6 as Compared With Baseline in Each Treatment Arm | The change in visual acuity (number of ETDRS - Early Treatment Diabetic Retinopathy Study letters), at Month 6 as compared with baseline in each treatment arm | Baseline - Month 6 |
| The Total Number of Additional Avastin Injections Following Initial Treatment in Each Treatment Arm | Total Number of addiitonal Avastin injections during study- From baseline to Month 6 | Baseline - Month 6 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Central Mean Thickness Based on OCT | Change in Central Mean Thickness based on OCT from baseline to Month 6t | Baseline to 6 Months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Macular Edema, Central Retinal Vein Occlusion
|
|
NCT00390299
|
Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme
|
This phase I trial studies the side effects and best dose of carcinoembryonic antigen-expressing measles virus (MV-CEA) in treating patients with glioblastoma multiforme that has come back. A virus, called MV-CEA, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells.
|
PRIMARY OBJECTIVES:~I. To assess the safety and toxicity of intratumoral and resection cavity administration of an Edmonston's strain measles virus genetically engineered to produce CEA (MV-CEA) in patients with recurrent glioblastoma multiforme.~II. To determine the maximum tolerated dose (MTD) of MV-CEA. III. To characterize viral gene expression at each dose level as manifested by CEA titers.~IV. To assess viremia, viral replication, and measles virus shedding/persistence following intratumoral administration.~V. To assess humoral and cellular immune response to the injected virus. VI. To assess in a preliminary fashion antitumor efficacy of this approach.~OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 sequential treatment arms.~ARM A (RESECTION CAVITY ADMINISTRATION): Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection cavity.~ARM B (INTRATUMORAL AND RESECTION CAVITY ADMINISTRATION): Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by carcinoembryonic antigen-expressing measles virus intratumorally (IT) through the catheter over 10 minutes on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed.~After completion of study treatment, patients are followed up at 28 days (non-cohort I patients), 7 weeks (patients in cohort I only), every 2 months until progression, every 3 and 12 months after progression, and then yearly thereafter for up to 15 years.
|
Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)
|
Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Mixed Glioma, Recurrent Glioblastoma
|
* Biological: Carcinoembryonic Antigen-Expressing Measles Virus
* Other: Laboratory Biomarker Analysis
* Procedure: Therapeutic Conventional Surgery
|
Inclusion Criteria:~Recurrent grade 3 or 4 glioma, including astrocytoma, oligodendroglioma or mixed glioma with histologic confirmation at initial diagnosis or recurrence~Candidate for gross total or subtotal resection~Absolute neutrophil count (ANC) >= 1500/uL~Platelets (PLT) >= 100,000/uL~Total bilirubin =< 1.5 x upper normal limit (ULN)~Aspartate aminotransferase (AST) =< 2 x ULN~Creatinine =< 2.0 x ULN~Hemoglobin (Hgb) >= 9.0 gm/dL~Prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.3 x ULN~Ability to provide informed consent~Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2~Anti-measles virus immunity as demonstrated by immunoglobulin G (IgG) anti-measles antibody levels of >= 1.1 EU/ml as determined by enzyme immunoassay~Normal serum CEA levels (< 3 ng/ml) at the time of registration~Willing to provide biologic specimens as required by the protocol~Negative serum pregnancy test done =< 7 days prior to registration (for women of childbearing potential only)~Exclusion Criteria:~Any of the following:~Pregnant women~Nursing women~Men or women of childbearing potential who are unwilling to employ adequate contraception~Active infection =< 5 days prior to registration~History of tuberculosis or history of purified protein derivative (PPD) positivity~Any of the following therapies:~Chemotherapy =< 4 weeks prior to registration (6 wks for nitrosourea-based chemotherapy)~Immunotherapy =< 4 weeks prior to registration~Biologic therapy =< 4 weeks prior to registration~Bevacizumab =< 12 weeks prior to registration~Non-cytotoxic antitumor drugs, i.e., small molecule cell cycle inhibitors =< 2 weeks prior to registration~Radiation therapy =< 6 weeks prior to registration~Any viral or gene therapy prior to registration~Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment~New York Heart Association classification III or IV~Requiring blood product support~Inadequate seizure control~Expected communication between ventricles and resection cavity as a result of surgery~Human immunodeficiency virus (HIV)-positive test result, or history of other immunodeficiency~History of organ transplantation~History of chronic hepatitis B or C~Other concurrent chemotherapy, immunotherapy, radiotherapy or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)~Exposure to household contacts =< 15 months old or household contact with known immunodeficiency~Allergy to measles vaccine or history of severe reaction to prior measles vaccination
|
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 |
| --- | --- | --- |
| Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I) Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities | The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include hematologic events grade 3 or higher (except grade 3 ANC lasting < 72 hours), non-hematologic events graded 3 or higher (except grade 3 nausea, vomiting, or diarrhea were to be considered DLT only if patient was receiving the max supportive care and alopecia was not considered dose limiting), neurologic toxicity grade 2 or higher, grade 2 allergic reactions asymptomatic bronchospasm and/or urticarial, grade 3 or higher allergic reactions, viremia lasting for 6 weeks or more from last viral administration deemed at least possibly related to treatment. The number of patients reporting a dose-limiting event are reported. | 2 weeks |
| Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0 | The number of patients experiencing grade 3+ adverse events (overall and by arm) will be tabulated and summarized in this patient population. | Up to 2 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence | The number of responses will be summarized by simple descriptive summary statistics delineating response type. CR = total disappearance of all tumor with patient off corticosteroids or only on adrenal replacement maintenance. PR= 50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions with the patient being on stable or decreased steroid dose. REGR = unequivocal reduction in size of contrast-enhancement or decrease in mass effect as agreed upon independently by primary physician and quality control physicians; no new lesions. SD = failure to qualify for CR, PR, REGR, or PROG. PROG = >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions and/or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions. | Up to 2 weeks |
| Progression-free Survival (PFS) | Percentage of patients who are progression free at 3 and 6 months (PFS3 and PFS6) will be summarized descriptively. Progression-free survival is defined as the length of time from date of registration to a) date of progression or death due to any cause or b) last follow-up. Progression is defined as a >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions, and/or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions. | Length of time from date of registration to a) date of progression or death due to any cause or b) last follow-up, assessed up to 6 months |
| Survival | Overall survival is defined as the length of time from date of registration to a) death due to any cause or b) last follow-up. Reported using standard Kaplan-Meier estimation method. | Up to 13 years |
|
Glioblastoma, Astrocytoma, Oligodendroglioma, Glioma, Recurrence, Disease Attributes, Pathologic Processes, 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: Arm A (resection cavity administration)<br>Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection cavity. | Biological: Carcinoembryonic Antigen-Expressing Measles Virus<br>* Given via injection into resection cavity or around tumor bed and/or IT<br>* Other names: MV-CEA;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Therapeutic Conventional Surgery<br>* Undergo en bloc resection<br>|
| Experimental: Arm B (intratumoral and resection cavity administration)<br>Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by MV-CEA IT through the catheter over 10 minutes on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed. | Biological: Carcinoembryonic Antigen-Expressing Measles Virus<br>* Given via injection into resection cavity or around tumor bed and/or IT<br>* Other names: MV-CEA;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Therapeutic Conventional Surgery<br>* Undergo en bloc resection<br>|
|
Viral Therapy in Treating Patients With Recurrent Glioblastoma Multiforme
Study Overview
=================
Brief Summary
-----------------
This phase I trial studies the side effects and best dose of carcinoembryonic antigen-expressing measles virus (MV-CEA) in treating patients with glioblastoma multiforme that has come back. A virus, called MV-CEA, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells.
Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To assess the safety and toxicity of intratumoral and resection cavity administration of an Edmonston's strain measles virus genetically engineered to produce CEA (MV-CEA) in patients with recurrent glioblastoma multiforme. II. To determine the maximum tolerated dose (MTD) of MV-CEA. III. To characterize viral gene expression at each dose level as manifested by CEA titers. IV. To assess viremia, viral replication, and measles virus shedding/persistence following intratumoral administration. V. To assess humoral and cellular immune response to the injected virus. VI. To assess in a preliminary fashion antitumor efficacy of this approach. OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 sequential treatment arms. ARM A (RESECTION CAVITY ADMINISTRATION): Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection cavity. ARM B (INTRATUMORAL AND RESECTION CAVITY ADMINISTRATION): Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by carcinoembryonic antigen-expressing measles virus intratumorally (IT) through the catheter over 10 minutes on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed. After completion of study treatment, patients are followed up at 28 days (non-cohort I patients), 7 weeks (patients in cohort I only), every 2 months until progression, every 3 and 12 months after progression, and then yearly thereafter for up to 15 years.
Official Title
-----------------
Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme (GBM)
Conditions
-----------------
Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Mixed Glioma, Recurrent Glioblastoma
Intervention / Treatment
-----------------
* Biological: Carcinoembryonic Antigen-Expressing Measles Virus
* Other: Laboratory Biomarker Analysis
* Procedure: Therapeutic Conventional Surgery
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Recurrent grade 3 or 4 glioma, including astrocytoma, oligodendroglioma or mixed glioma with histologic confirmation at initial diagnosis or recurrence Candidate for gross total or subtotal resection Absolute neutrophil count (ANC) >= 1500/uL Platelets (PLT) >= 100,000/uL Total bilirubin =< 1.5 x upper normal limit (ULN) Aspartate aminotransferase (AST) =< 2 x ULN Creatinine =< 2.0 x ULN Hemoglobin (Hgb) >= 9.0 gm/dL Prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.3 x ULN Ability to provide informed consent Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 Anti-measles virus immunity as demonstrated by immunoglobulin G (IgG) anti-measles antibody levels of >= 1.1 EU/ml as determined by enzyme immunoassay Normal serum CEA levels (< 3 ng/ml) at the time of registration Willing to provide biologic specimens as required by the protocol Negative serum pregnancy test done =< 7 days prior to registration (for women of childbearing potential only) Exclusion Criteria: Any of the following: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Active infection =< 5 days prior to registration History of tuberculosis or history of purified protein derivative (PPD) positivity Any of the following therapies: Chemotherapy =< 4 weeks prior to registration (6 wks for nitrosourea-based chemotherapy) Immunotherapy =< 4 weeks prior to registration Biologic therapy =< 4 weeks prior to registration Bevacizumab =< 12 weeks prior to registration Non-cytotoxic antitumor drugs, i.e., small molecule cell cycle inhibitors =< 2 weeks prior to registration Radiation therapy =< 6 weeks prior to registration Any viral or gene therapy prior to registration Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment New York Heart Association classification III or IV Requiring blood product support Inadequate seizure control Expected communication between ventricles and resection cavity as a result of surgery Human immunodeficiency virus (HIV)-positive test result, or history of other immunodeficiency History of organ transplantation History of chronic hepatitis B or C Other concurrent chemotherapy, immunotherapy, radiotherapy or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) Exposure to household contacts =< 15 months old or household contact with known immunodeficiency Allergy to measles vaccine or history of severe reaction to prior measles vaccination
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: Arm A (resection cavity administration)<br>Patients undergo en block resection of their tumor (after confirming diagnosis) on day 1, followed by MV-CEA administered into the resection cavity. | Biological: Carcinoembryonic Antigen-Expressing Measles Virus<br>* Given via injection into resection cavity or around tumor bed and/or IT<br>* Other names: MV-CEA;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Therapeutic Conventional Surgery<br>* Undergo en bloc resection<br>|
| Experimental: Arm B (intratumoral and resection cavity administration)<br>Patients undergo stereotactic biopsy (to confirm the diagnosis) and placement of a catheter within the tumor, followed by MV-CEA IT through the catheter over 10 minutes on day 1. Patients then undergo en block resection of their tumor with computer-assisted stereotactic techniques on day 5, followed by MV-CEA administered around the tumor bed. | Biological: Carcinoembryonic Antigen-Expressing Measles Virus<br>* Given via injection into resection cavity or around tumor bed and/or IT<br>* Other names: MV-CEA;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Therapeutic Conventional Surgery<br>* Undergo en bloc resection<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I) Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities | The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include hematologic events grade 3 or higher (except grade 3 ANC lasting < 72 hours), non-hematologic events graded 3 or higher (except grade 3 nausea, vomiting, or diarrhea were to be considered DLT only if patient was receiving the max supportive care and alopecia was not considered dose limiting), neurologic toxicity grade 2 or higher, grade 2 allergic reactions asymptomatic bronchospasm and/or urticarial, grade 3 or higher allergic reactions, viremia lasting for 6 weeks or more from last viral administration deemed at least possibly related to treatment. The number of patients reporting a dose-limiting event are reported. | 2 weeks |
| Number of Patients Experiencing Grade 3+ Adverse Events, Per NCI CTCAE Version 3.0 | The number of patients experiencing grade 3+ adverse events (overall and by arm) will be tabulated and summarized in this patient population. | Up to 2 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response, Defined as the Best Objective Status Recorded From the Start of the Treatment Until Disease Progression/Recurrence | The number of responses will be summarized by simple descriptive summary statistics delineating response type. CR = total disappearance of all tumor with patient off corticosteroids or only on adrenal replacement maintenance. PR= 50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions with the patient being on stable or decreased steroid dose. REGR = unequivocal reduction in size of contrast-enhancement or decrease in mass effect as agreed upon independently by primary physician and quality control physicians; no new lesions. SD = failure to qualify for CR, PR, REGR, or PROG. PROG = >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions and/or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions. | Up to 2 weeks |
| Progression-free Survival (PFS) | Percentage of patients who are progression free at 3 and 6 months (PFS3 and PFS6) will be summarized descriptively. Progression-free survival is defined as the length of time from date of registration to a) date of progression or death due to any cause or b) last follow-up. Progression is defined as a >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions, and/or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions. | Length of time from date of registration to a) date of progression or death due to any cause or b) last follow-up, assessed up to 6 months |
| Survival | Overall survival is defined as the length of time from date of registration to a) death due to any cause or b) last follow-up. Reported using standard Kaplan-Meier estimation method. | Up to 13 years |
|
|
NCT05210881
|
Weaning From Nasal High Flow Therapy
|
Nasal high flow is widely used in critically ill patients admitted to the intensive care unit (ICU) for acute hypoxemic respiratory failure. It has been shown to improve patient comfort, increase oxygenation and reduce need for intubation in some patients. The Respiratory Oxygenation (ROX) index has been established as a simple tool to help clinicians identify those patients who will succeed and those who will fail under nasal high flow and therefore predict the need for intubation. However, when nasal high flow therapy is successful, little is known as to how and when weaning of this device should be performed and what are the predictors of a safe withdrawal of the device. The objectives of this retrospective exploratory study are to identify a cut-off value of the ROX index predictive of success of the withdrawal trial, to describe a one-year use of the withdrawal trial; to describe the ROX value closest to weaning from nasal high flow, and to identify factors associated with success or failure of the withdrawal trial from nasal high flow therapy in patients receiving nasal high flow therapy.
|
Although nasal high flow is widely used in critically ill patients admitted to the intensive care unit (ICU) for acute hypoxemic respiratory failure, and its benefits have been shown in multiple studies, little is known as to how and when weaning from the technique device should be performed and what are the predictors of a safe withdrawal. The Respiratory Oxygenation (ROX) index was established and tested to predict outcome of nasal high flow therapy in patients with acute hypoxemic respiratory failure. It combines three parameters available at the bedside that reflect patient's respiratory status: respiratory rate, the level of the inspired fraction of oxygen (FiO2) and pulse oximetry (SpO2). Importantly, the combination of these three parameters outweighed the performance of each parameter taken separately to predict nasal high flow therapy outcome. Since its initial publication, several studies coming from different countries have confirmed the potential for the ROX index to predict need for intubation in patients with acute hypoxemic respiratory failure, thus making a valuable tool accessible to everyone, including nurses, to monitor on a routine basis. Because it reflects the patient's respiratory status, the greater the score, the better the patient's condition. Hence, one may hypothesize that, at the other end of the spectrum of respiratory failure (i.e., at the stage of weaning and withdrawal of the high flow device when the patient has considerably improved), the ROX index may also help identify those patients who will be successfully separated from the nasal high flow support. To date, one study has suggested that among several parameters, the value of the ROX index could be associated with successful cessation of nasal high flow. Here, in a retrospective exploratory study, investigators aim to to identify a cut-off value of the ROX index predictive of success of the withdrawal trial, to describe a one-year use of the withdrawal trial (average duration of use of nasal high flow before weaning, number of weaning trials, number of failed and successful weaning trials.); to describe the ROX value closest to weaning from nasal high flow, and to identify factors associated with success or failure of the withdrawal trial from nasal high flow therapy in patients receiving nasal high flow therapy; A successful withdrawal is defined as the withdrawal of nasal high flow without necessity of placing the patient back on nasal high flow within the following 24h. A failed withdrawal is defined by the need to resume nasal high flow within the 24h hours following the withdrawal. The possible identification of a cut-off value may help clinicians initiate earlier weaning from nasal high flow.
|
Weaning From Nasal High Flow Therapy: an Explorative Study Assessing the Usefulness of the ROX Index to Predict Outcome of the Weaning Process in Combination With a Withdrawal Trial
|
Respiratory Distress Syndrome, Adult, Acute Hypoxemic Respiratory Failure, Acute Respiratory Distress Syndrome, Weaning Failure
|
Inclusion Criteria:~- ICU patient treated with nasal high flow~Exclusion Criteria:~age < 18 years~concomitant treatment with non-invasive ventilation~acute hypercapnic respiratory failure
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Value of the Respiratory Oxygenation index (ROX) at nasal high flow withdrawal | the ROX index the closest to the time at which nasal high flow is withdrawn will be recorded | through each nasal high flow therapy, that lasts an average of 24hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| use of nasal high flow before weaning | average duration of nasal high flow therapy before initiating a withdrawal trial (in hours) | through each nasal high flow therapy, that lasts an average of 24 hours |
| number of withdrawal trials | the number of trials each patient will have performed will be recorded | through each nasal high flow therapy, that lasts an average of 24 hours |
| number of patients who failed a withdrawal trial | withdrawal failure is defined by patients who required to be placed back on nasal high flow after withdrawal of the high flow device within 24 hours of withdrawal. | throughout study duration which is a one-year period |
| number of patients who succeeded a withdrawal trial | withdrawal success is defined by patients that have not required to be placed back on nasal high flow after withdrawal of the high flow device within 24 hours of withdrawal. | throughout study duration which is a one-year period |
|
nasal high flow oxygen, withdrawal from nasal high flow therapy, ROX index, acute hypoxemic respiratory failure, withdrawal trial
|
Respiratory Distress Syndrome, Respiratory Distress Syndrome, Newborn, Respiratory Insufficiency, Acute Lung Injury, Syndrome, Disease, Pathologic Processes, Lung Diseases, Respiratory Tract Diseases, Respiration Disorders, Infant, Premature, Diseases, Infant, Newborn, Diseases, Lung Injury
|
Weaning From Nasal High Flow Therapy
Study Overview
=================
Brief Summary
-----------------
Nasal high flow is widely used in critically ill patients admitted to the intensive care unit (ICU) for acute hypoxemic respiratory failure. It has been shown to improve patient comfort, increase oxygenation and reduce need for intubation in some patients. The Respiratory Oxygenation (ROX) index has been established as a simple tool to help clinicians identify those patients who will succeed and those who will fail under nasal high flow and therefore predict the need for intubation. However, when nasal high flow therapy is successful, little is known as to how and when weaning of this device should be performed and what are the predictors of a safe withdrawal of the device. The objectives of this retrospective exploratory study are to identify a cut-off value of the ROX index predictive of success of the withdrawal trial, to describe a one-year use of the withdrawal trial; to describe the ROX value closest to weaning from nasal high flow, and to identify factors associated with success or failure of the withdrawal trial from nasal high flow therapy in patients receiving nasal high flow therapy.
Detailed Description
-----------------
Although nasal high flow is widely used in critically ill patients admitted to the intensive care unit (ICU) for acute hypoxemic respiratory failure, and its benefits have been shown in multiple studies, little is known as to how and when weaning from the technique device should be performed and what are the predictors of a safe withdrawal. The Respiratory Oxygenation (ROX) index was established and tested to predict outcome of nasal high flow therapy in patients with acute hypoxemic respiratory failure. It combines three parameters available at the bedside that reflect patient's respiratory status: respiratory rate, the level of the inspired fraction of oxygen (FiO2) and pulse oximetry (SpO2). Importantly, the combination of these three parameters outweighed the performance of each parameter taken separately to predict nasal high flow therapy outcome. Since its initial publication, several studies coming from different countries have confirmed the potential for the ROX index to predict need for intubation in patients with acute hypoxemic respiratory failure, thus making a valuable tool accessible to everyone, including nurses, to monitor on a routine basis. Because it reflects the patient's respiratory status, the greater the score, the better the patient's condition. Hence, one may hypothesize that, at the other end of the spectrum of respiratory failure (i.e., at the stage of weaning and withdrawal of the high flow device when the patient has considerably improved), the ROX index may also help identify those patients who will be successfully separated from the nasal high flow support. To date, one study has suggested that among several parameters, the value of the ROX index could be associated with successful cessation of nasal high flow. Here, in a retrospective exploratory study, investigators aim to to identify a cut-off value of the ROX index predictive of success of the withdrawal trial, to describe a one-year use of the withdrawal trial (average duration of use of nasal high flow before weaning, number of weaning trials, number of failed and successful weaning trials.); to describe the ROX value closest to weaning from nasal high flow, and to identify factors associated with success or failure of the withdrawal trial from nasal high flow therapy in patients receiving nasal high flow therapy; A successful withdrawal is defined as the withdrawal of nasal high flow without necessity of placing the patient back on nasal high flow within the following 24h. A failed withdrawal is defined by the need to resume nasal high flow within the 24h hours following the withdrawal. The possible identification of a cut-off value may help clinicians initiate earlier weaning from nasal high flow.
Official Title
-----------------
Weaning From Nasal High Flow Therapy: an Explorative Study Assessing the Usefulness of the ROX Index to Predict Outcome of the Weaning Process in Combination With a Withdrawal Trial
Conditions
-----------------
Respiratory Distress Syndrome, Adult, Acute Hypoxemic Respiratory Failure, Acute Respiratory Distress Syndrome, Weaning Failure
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - ICU patient treated with nasal high flow Exclusion Criteria: age < 18 years concomitant treatment with non-invasive ventilation acute hypercapnic respiratory 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?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Value of the Respiratory Oxygenation index (ROX) at nasal high flow withdrawal | the ROX index the closest to the time at which nasal high flow is withdrawn will be recorded | through each nasal high flow therapy, that lasts an average of 24hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| use of nasal high flow before weaning | average duration of nasal high flow therapy before initiating a withdrawal trial (in hours) | through each nasal high flow therapy, that lasts an average of 24 hours |
| number of withdrawal trials | the number of trials each patient will have performed will be recorded | through each nasal high flow therapy, that lasts an average of 24 hours |
| number of patients who failed a withdrawal trial | withdrawal failure is defined by patients who required to be placed back on nasal high flow after withdrawal of the high flow device within 24 hours of withdrawal. | throughout study duration which is a one-year period |
| number of patients who succeeded a withdrawal trial | withdrawal success is defined by patients that have not required to be placed back on nasal high flow after withdrawal of the high flow device within 24 hours of withdrawal. | throughout study duration which is a one-year period |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
nasal high flow oxygen, withdrawal from nasal high flow therapy, ROX index, acute hypoxemic respiratory failure, withdrawal trial
|
|||
NCT04171505
|
Retrospective Cohort Study of the Effectiveness of the Prophylactic Vaccine Against the Human Papilloma Virus in the Prevention of Recurrence in Women Who Have Received an Excisional Therapy by HSIL / CIN.
|
A retrospective cohort study of women treated by excisional therapy due to HSIL/ CIN at Clínico San Carlos Hospital between 2012-2018. The effectiveness of prophylactic vaccination against HPV in women treated for HPV-related disease will be evaluated. For this purpose, the percentage of cervical lesion recurrence among a group of treated and vaccinated women against HPV between the years 2015-2018 will be compared with a control group of treated and non-vaccinated women against HPV since 2012-2015.~It will be an essential requirement that the patient provide a vaccination card from their health center where there is proof of their immunization status and date of administration.~Inclusion criteria:~Women older than 18 years who received excisional therapy due to HSIL /CIN injury confirmed histologically.~Women who sign informed consent.~Patients with negative results in the first post-surgery control.~Patients who have received HPV vaccination and provide vaccination card.~Exclusion criteria:~Women who do not wish or cannot give their informed consent and / or do not comply with the requirements of the study.~Patients treated by an indication other than HSIL/CIN.~Patients under immunosuppression conditions.
|
A retrospective cohort study of women treated by excisional therapy due to HSIL/ CIN at Clínico San Carlos Hospital (Madrid) between 2012-2018. The effectiveness of prophylactic vaccination against HPV in women treated for HPV-linked disease will be evaluated. For this purpose, the percentage of lesional recurrence among a group of treated and vaccinated women against HPV between the years 2015-2018 will be compared with a control group of treated and non-vaccinated women against HPV since 2012-2015. The data will be obtained through the review of clinical records.~Our protocol is explained above:~HPV detection method:~The detection of HPV is performed on a liquid basis by means of the CLARK PAPILOMAVIRUS HUMAN test that detects the presence of the HPV virus (6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 61, 62, 66, 68, 70, 71.72, 73, 81, 82, 83, 84, 85 and 89). The test has a diagnostic sensitivity of 98.2% and a diagnostic specificity of 100% and analytical specificity: 100%. The analytical sensitivity of this test is 100% when the number of copies is 1,000 or 10,000 depending on the type of HPV. The Laboratory has carried out external quality control of the SEAP.~Pre-surgical evaluation:~Those patients with an abnormal cytological result and / or positive HPV tests were referred to the PTGI consultations of Clínico San Carlos Hospital for evaluation according to the Cervical Cancer Prevention Guidelines issued by the Spanish Association of Cervical Pathology and Colposcopy (AEPCC) in 2006 and 2014. These patients underwent colposcopy with biopsy if necessary +/- determination of HPV. Patients diagnosed with HSIL / CIN 2+ who met the inclusion criteria were submitted to cervical conization and subsequently enrolled in the study after signing the informed consent, approved by ethics commission.~We will take into account the date of administration of the first dose of vaccine. The types of vaccines administered can be: Bivalent vaccine (includes genotypes 16/18), Tetravalent (includeds genotypes 6, 11, 16 and 18) both funded in the region in different years, or not funded (Nonavalent vaccine; includes genotypes: 6, 11, 16, 18, 31, 33, 45, 52 and 58). To define the time of vaccination around the conization date, the administration of the first dose of vaccine will be taken into account.~Surgical treatment:~Excisional therapy was performed in the operating room on a scheduled basis under local analgesia and sedation. After infiltration with local anesthetic and vasoconstrictor in the 4 quadrants of the cervix, excisional therapy with diathermic loop is performed under colposcopy control, obtaining the piece in a single specimen. The piece is oriented with a long thread at 12:00 h, it is introduced in formaldehyde and send to pathological anatomy for deferred study. In all cases, immediate endocervical curettage post-treatment was performed.~Clinical follow-up:~The first revision is made 30 days after surgery where patient is informed of histological results and the date on first control post-treatment based on the diagnosis.~Following the protocol of the AEPCC, in case of non-involvement of margins and negative endocervical curettage, the patient comes after 6 months from the intervention to perform the first post-surgery control with co-test. In case of positive endocervical curettage or margin involvement, the first post-surgery control will be performed at 4 months with cotest + endocervical study and colposcopy. Persistent disease is defined as the presence of cytological alteration and / or HPV infection in the first post control performed at 4-6 months after excisional therapy. These patients are excluded from the study, since only those in which both tests are negative will be included.~Subsequently, a new co-test was performed at 12 months, 24 months and 36 months after the first post-surgery control. After 3 years of negative testing, the patient is returned to the current cervical cancer-screening program.
|
Retrospective Cohort Study to Analyze Whether Prophylactic Vaccination Against HPV Can Reduce the Risk of Recurrence in Women Who Have Received an Excisional Therapy for HSIL / CIN2-3. Recurrence is Defined as the Detection of Infection by the Same HPV Genotype for at Least 6-12 Months (Persistent Infection), and / or Cytological Alteration and / or Cervical and / or Vaginal Histological Lesion of Any Grade (SIL / CIN / VaIN) in Patients With Negative Cotest in the First Post Control.
|
Cervix, Dysplasia, HPV Infection, HPV Vaccine, Cervix Lesion
|
* Drug: HPV vaccine
|
Inclusion Criteria:~Women older than 18 years who received excisional therapy due to HSIL /CIN injury confirmed histologically.~Women who sign informed consent.~Patients with negative results in the first post-surgery control.~Patients who have received HPV vaccination and provide vaccination card.~Exclusion Criteria:~Women who do not wish or cannot give their informed consent and / or do not comply with the requirements of the study.~Patients treated by an indication other than HSIL/CIN.~Patients under immunosuppression conditions.
|
18 Years
|
100 Years
|
Female
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence | defined as the existence of persistent HPV infection and / or presence of cytological abnormality and / or presence of SIL / CIN / VaIN of any grade. | 2 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Age, type of virus, degree of injury, variables related to demographic and histological data of the patient, date of 1st dose of vaccine. | | 2 years |
|
Infections, Papillomavirus Infections, Recurrence, Communicable Diseases, Disease Attributes, Pathologic Processes, Sexually Transmitted Diseases, Viral, Sexually Transmitted Diseases, DNA Virus Infections, Virus Diseases, Tumor Virus Infections, Genital Diseases, Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| vaccinated women<br>Women older than 18 years who received excisional therapy due to HSIL /CIN injury confirmed histologically.~Women who sign informed consent.~Patients with negative results in the first post-surgery control.~Patients who have received HPV vaccination and provide vaccination card. | Drug: HPV vaccine<br>* . Patients diagnosed with HSIL / CIN 2+ who met the inclusion criteria were submitted to cervical conization and subsequently enrolled in the study after signing the informed consent, approved by ethics commission.~We will take into account the date of administration of the first dose of vaccine. The types of vaccines administered can be: Bivalent vaccine (includes genotypes 16/18), Tetravalent (includeds genotypes 6, 11, 16 and 18) both funded in the region in different years, or not funded (Nonavalent vaccine; includes genotypes: 6, 11, 16, 18, 31, 33, 45, 52 and 58). To define the time of vaccination around the conization date, the administration of the first dose of vaccine will be taken into account.<br>|
| non vaccinated woman<br>Women older than 18 years who received excisional therapy due to HSIL /CIN injury confirmed histologically.~Women who sign informed consent.~Patients with negative results in the first post-surgery control.~Patients who have NOT received HPV vaccination and provide vaccination card. | |
|
Retrospective Cohort Study of the Effectiveness of the Prophylactic Vaccine Against the Human Papilloma Virus in the Prevention of Recurrence in Women Who Have Received an Excisional Therapy by HSIL / CIN.
Study Overview
=================
Brief Summary
-----------------
A retrospective cohort study of women treated by excisional therapy due to HSIL/ CIN at Clínico San Carlos Hospital between 2012-2018. The effectiveness of prophylactic vaccination against HPV in women treated for HPV-related disease will be evaluated. For this purpose, the percentage of cervical lesion recurrence among a group of treated and vaccinated women against HPV between the years 2015-2018 will be compared with a control group of treated and non-vaccinated women against HPV since 2012-2015. It will be an essential requirement that the patient provide a vaccination card from their health center where there is proof of their immunization status and date of administration. Inclusion criteria: Women older than 18 years who received excisional therapy due to HSIL /CIN injury confirmed histologically. Women who sign informed consent. Patients with negative results in the first post-surgery control. Patients who have received HPV vaccination and provide vaccination card. Exclusion criteria: Women who do not wish or cannot give their informed consent and / or do not comply with the requirements of the study. Patients treated by an indication other than HSIL/CIN. Patients under immunosuppression conditions.
Detailed Description
-----------------
A retrospective cohort study of women treated by excisional therapy due to HSIL/ CIN at Clínico San Carlos Hospital (Madrid) between 2012-2018. The effectiveness of prophylactic vaccination against HPV in women treated for HPV-linked disease will be evaluated. For this purpose, the percentage of lesional recurrence among a group of treated and vaccinated women against HPV between the years 2015-2018 will be compared with a control group of treated and non-vaccinated women against HPV since 2012-2015. The data will be obtained through the review of clinical records. Our protocol is explained above: HPV detection method: The detection of HPV is performed on a liquid basis by means of the CLARK PAPILOMAVIRUS HUMAN test that detects the presence of the HPV virus (6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 56, 58, 59, 61, 62, 66, 68, 70, 71.72, 73, 81, 82, 83, 84, 85 and 89). The test has a diagnostic sensitivity of 98.2% and a diagnostic specificity of 100% and analytical specificity: 100%. The analytical sensitivity of this test is 100% when the number of copies is 1,000 or 10,000 depending on the type of HPV. The Laboratory has carried out external quality control of the SEAP. Pre-surgical evaluation: Those patients with an abnormal cytological result and / or positive HPV tests were referred to the PTGI consultations of Clínico San Carlos Hospital for evaluation according to the Cervical Cancer Prevention Guidelines issued by the Spanish Association of Cervical Pathology and Colposcopy (AEPCC) in 2006 and 2014. These patients underwent colposcopy with biopsy if necessary +/- determination of HPV. Patients diagnosed with HSIL / CIN 2+ who met the inclusion criteria were submitted to cervical conization and subsequently enrolled in the study after signing the informed consent, approved by ethics commission. We will take into account the date of administration of the first dose of vaccine. The types of vaccines administered can be: Bivalent vaccine (includes genotypes 16/18), Tetravalent (includeds genotypes 6, 11, 16 and 18) both funded in the region in different years, or not funded (Nonavalent vaccine; includes genotypes: 6, 11, 16, 18, 31, 33, 45, 52 and 58). To define the time of vaccination around the conization date, the administration of the first dose of vaccine will be taken into account. Surgical treatment: Excisional therapy was performed in the operating room on a scheduled basis under local analgesia and sedation. After infiltration with local anesthetic and vasoconstrictor in the 4 quadrants of the cervix, excisional therapy with diathermic loop is performed under colposcopy control, obtaining the piece in a single specimen. The piece is oriented with a long thread at 12:00 h, it is introduced in formaldehyde and send to pathological anatomy for deferred study. In all cases, immediate endocervical curettage post-treatment was performed. Clinical follow-up: The first revision is made 30 days after surgery where patient is informed of histological results and the date on first control post-treatment based on the diagnosis. Following the protocol of the AEPCC, in case of non-involvement of margins and negative endocervical curettage, the patient comes after 6 months from the intervention to perform the first post-surgery control with co-test. In case of positive endocervical curettage or margin involvement, the first post-surgery control will be performed at 4 months with cotest + endocervical study and colposcopy. Persistent disease is defined as the presence of cytological alteration and / or HPV infection in the first post control performed at 4-6 months after excisional therapy. These patients are excluded from the study, since only those in which both tests are negative will be included. Subsequently, a new co-test was performed at 12 months, 24 months and 36 months after the first post-surgery control. After 3 years of negative testing, the patient is returned to the current cervical cancer-screening program.
Official Title
-----------------
Retrospective Cohort Study to Analyze Whether Prophylactic Vaccination Against HPV Can Reduce the Risk of Recurrence in Women Who Have Received an Excisional Therapy for HSIL / CIN2-3. Recurrence is Defined as the Detection of Infection by the Same HPV Genotype for at Least 6-12 Months (Persistent Infection), and / or Cytological Alteration and / or Cervical and / or Vaginal Histological Lesion of Any Grade (SIL / CIN / VaIN) in Patients With Negative Cotest in the First Post Control.
Conditions
-----------------
Cervix, Dysplasia, HPV Infection, HPV Vaccine, Cervix Lesion
Intervention / Treatment
-----------------
* Drug: HPV vaccine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women older than 18 years who received excisional therapy due to HSIL /CIN injury confirmed histologically. Women who sign informed consent. Patients with negative results in the first post-surgery control. Patients who have received HPV vaccination and provide vaccination card. Exclusion Criteria: Women who do not wish or cannot give their informed consent and / or do not comply with the requirements of the study. Patients treated by an indication other than HSIL/CIN. Patients under immunosuppression conditions.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| vaccinated women<br>Women older than 18 years who received excisional therapy due to HSIL /CIN injury confirmed histologically. Women who sign informed consent. Patients with negative results in the first post-surgery control. Patients who have received HPV vaccination and provide vaccination card. | Drug: HPV vaccine<br>* . Patients diagnosed with HSIL / CIN 2+ who met the inclusion criteria were submitted to cervical conization and subsequently enrolled in the study after signing the informed consent, approved by ethics commission. We will take into account the date of administration of the first dose of vaccine. The types of vaccines administered can be: Bivalent vaccine (includes genotypes 16/18), Tetravalent (includeds genotypes 6, 11, 16 and 18) both funded in the region in different years, or not funded (Nonavalent vaccine; includes genotypes: 6, 11, 16, 18, 31, 33, 45, 52 and 58). To define the time of vaccination around the conization date, the administration of the first dose of vaccine will be taken into account.<br>|
| non vaccinated woman<br>Women older than 18 years who received excisional therapy due to HSIL /CIN injury confirmed histologically. Women who sign informed consent. Patients with negative results in the first post-surgery control. Patients who have NOT received HPV vaccination and provide vaccination card. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence | defined as the existence of persistent HPV infection and / or presence of cytological abnormality and / or presence of SIL / CIN / VaIN of any grade. | 2 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Age, type of virus, degree of injury, variables related to demographic and histological data of the patient, date of 1st dose of vaccine. | | 2 years |
|
||
NCT05086913
|
Self-help Lifestyle Medicine App and Booklets for Depression
|
This study aims to compare self-help lifestyle medicine (LM) delivered by a smartphone app and booklets in managing depressive symptoms in a Chinese population.~This study is a randomised controlled trial. First, informed consent will be obtained from potential participants. Around 90 eligible participants will be randomly assigned to either the LM app group, the LM booklet group, and the waitlist control group, in a ratio of 1:1:1. The app group will receive an app to facilitate lifestyle modification such as video demonstrations of physical activity, diet recommendations, stress and sleep management. The booklet group will receive 8 LM booklets with identical content with the LM app. The waitlist control group will receive access to the app and booklets at the end of the study. The whole intervention lasts 8 weeks. Participants will also receive 2 messages per week from the researcher to check and prompt motivation and adherence. Participants will complete assessment before, immediately after intervention, at one month and 12-week follow up.
|
As lifestyle plays an important role in the pathogenesis of depression, lifestyle medicine (LM) emerges as a new way to alleviate depressive symptoms (Sarris & O'Neil, 2016). Booklets have been shown as an inexpensive and effective delivery modality of lifestyle modification among individuals with physical conditions (Wong, Chair & Wong, 2017). Meanwhile, a recent meta-analysis supports the efficacy of mobile applications in improving depressive symptoms (Linardon, Cujipers, Carlbring, Messer & Fuller-Tyszkiewicz, 2019). Notably, the efficacy of lifestyle intervention using booklets and app have not been compared. This pilot study can inform the field about the efficacy of lifestyle intervention using two self-help delivery modalities and offer new ways to better managing depressive symptoms.~This study will be a randomised controlled trial comparing self-help LM delivered by a smartphone app and booklets in improving depression. For a pilot study, a sample size of 12 per group is recommended (Julious, 2005). Considering an estimation of 20% attrition at the three assessment time points, the final sample size is 90, with 30 participants in each group.~The LM booklet group will receive a pocket size 6-page booklet weekly that covers 8 lifestyle medicine themes including stress, relaxation, diet, exercise, sleep hygiene, worry management, mindfulness, and positive psychology. Exercises based on cognitive behavioural therapy and guidance to set and meet short term and long-term goals are featured in the booklets. The booklet series is reviewed by a panel of experts including clinical psychologists, psychiatrists, dietitians, physical trainers, and traditional Chinese Medicine practitioners. The app group will receive access to a mobile app that offers 8 modules with identical content as the wellness booklets, in addition to videos, relaxation, exercise and cooking demonstrations, daily challenges and record of goals. The waitlist control group will receive access to the app and booklets at the end of the study.
|
A Comparison of Self-help Lifestyle Modification Delivered by a Smartphone App and Booklets in Managing Depressive Symptoms: a Pilot Randomised Controlled Trial.
|
Depression
|
* Other: Lifestyle medicine smartphone booklets
* Other: Lifestyle medicine smartphone app
* Other: Waitlist control
|
Inclusion Criteria:~Participants with elevated depressive symptoms as defined by PHQ-9 score 10 or above~Hong Kong residents~Aged 18 or above~Able to read Chinese and type in Chinese or English~Have an Internet-enabled mobile device (iOS or Android operating system)~Exclusion Criteria:~Pregnancy;~Using medication or psychotherapy for depression;~Currently participating in other psychological intervention studies;~Cognitive impairment;~Having unsafe conditions and are not recommended for physical activity or a change in diet by physicians;~Self-disclosure of any major psychiatric, medical, or neurocognitive disorders that make participation unsuitable or may interfere with the adherence of the lifestyle modification;~Any suicidal ideation (scoring above 2 in item 9 in BDI-II) Participants with any urgent health necessity were excluded and referred.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Patient Health Questionnaire (PHQ-9) | The PHQ-9, a 20-item questionnaire used for screening, diagnosing, monitoring and measuring the severity of depression, which scores each of the nine DSM-IV criteria as 0 (not at all) to 3 (nearly every day). | baseline, immediately post-intervention, 4-week and 12-week follow-up |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-developed survey | A self-developed survey will collect information including demographic information (e.g., age, gender, level of education, working industry, relationship status, and location of residence), substance use, body mass index (BMI), rest-activity pattern, and social rhythms, etc. | Baseline |
| Change in the World Health Organization 5-item Well-Being Index | This is a 5-item measure of global subjective well-being. The internal consistency prior to treatment was 0.86. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Short Form (Six-Dimension) Health Survey (SF-6D) | SF-6D is a preference-based single index measure of health. A six-digit number represents each SF-6D health state, each digit denotes the level of one of six SF-6D dimensions: physical functioning, role limitation, social functioning, bodily pain, mental health, and vitality. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Perceived Stress Scale (PSS) | The PSS measures the perceived amount of stress experienced over the past month. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Generalized Anxiety Disorder 7-Item Scale (GAD-7) | The GAD-7, a 7-item questionnaire used for screening, diagnosing, monitoring and measuring the severity of anxiety over the past two weeks on a 4-point scale, 0 (not at all) to 4 (nearly every day). | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Sheehan Disability Scale (SDS) | SDS is a brief, 5-item self-report tool that assesses functional impairment in work/school, social life, and family life. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Health-Promoting Lifestyle Profile (HPLP II) | The 52-item HPLPII is composed of a total scale and six subscales to measure behaviors in the theorized dimensions of health-promoting lifestyle: spiritual growth, interpersonal relations, nutrition, physical activity, health responsibility, and stress management. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the International Physical Activities Questionnaire - Chinese version (IPAQ-C) | Participants' sitting time, walking time and moderate and vigorous physical activity are assessed by 5 questions from the short form of the International Physical Activity Questionnaire - Chinese version. Participants' engagement in brief strength and stamina-enhancing activity were assessed by asking the number of days they engaged in physical activity while seated and standing in the last seven days. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Insomnia Severity Index (ISI) | The ISI is a 7-item scale designed to evaluate perceived insomnia severity. Ratings on the 5-point Likert scale are obtained on the perceived severity of sleep-onset, sleep-maintenance, early morning awakening problems, satisfaction with current sleep pattern, interference with daily functioning, noticeably of impairment attributed to the sleep problem, and level of distress caused by the sleep problem. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
|
Depression, Self-help, Lifestyle Medicine, Well-being
|
Depression, Depressive Disorder, Behavioral Symptoms, Mood Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lifestyle medicine smartphone app<br>The app group will receive an app to facilitate lifestyle modification such as video demonstrations of physical activity, diet recommendations, stress and sleep management. | Other: Lifestyle medicine smartphone app<br>* The lifestyle medicine app offers 8 modules with identical content as the wellness booklets, in addition to videos, relaxation, exercise and cooking demonstrations, daily challenges, record of goals, and ecological momentary assessments of diet, physical activity, sleep, stress and mood.<br>|
| Experimental: lifestyle medicine booklets<br>The booklet group will receive 8 lifestyle medicine and psychoeducation booklets with identical content with the lifestyle medicine app. | Other: Lifestyle medicine smartphone booklets<br>* Participants will receive a pocket size 6-page booklet weekly over 8 weeks that covers 8 lifestyle medicine, mental health and CBT themes including stress, relaxation, diet, exercise, sleep hygiene, worry management, mindfulness, and positive psychology, and guides participants to set and meet short term and long-term goals.<br>|
| Sham Comparator: waitlist control<br>The waitlist control group will receive access to the lifestyle medicine app and booklets at the end of the study. | Other: Waitlist control<br>* The waitlist control group will receive access to the lifestyle medicine app and booklets at the end of the study.<br>|
|
Self-help Lifestyle Medicine App and Booklets for Depression
Study Overview
=================
Brief Summary
-----------------
This study aims to compare self-help lifestyle medicine (LM) delivered by a smartphone app and booklets in managing depressive symptoms in a Chinese population. This study is a randomised controlled trial. First, informed consent will be obtained from potential participants. Around 90 eligible participants will be randomly assigned to either the LM app group, the LM booklet group, and the waitlist control group, in a ratio of 1:1:1. The app group will receive an app to facilitate lifestyle modification such as video demonstrations of physical activity, diet recommendations, stress and sleep management. The booklet group will receive 8 LM booklets with identical content with the LM app. The waitlist control group will receive access to the app and booklets at the end of the study. The whole intervention lasts 8 weeks. Participants will also receive 2 messages per week from the researcher to check and prompt motivation and adherence. Participants will complete assessment before, immediately after intervention, at one month and 12-week follow up.
Detailed Description
-----------------
As lifestyle plays an important role in the pathogenesis of depression, lifestyle medicine (LM) emerges as a new way to alleviate depressive symptoms (Sarris & O'Neil, 2016). Booklets have been shown as an inexpensive and effective delivery modality of lifestyle modification among individuals with physical conditions (Wong, Chair & Wong, 2017). Meanwhile, a recent meta-analysis supports the efficacy of mobile applications in improving depressive symptoms (Linardon, Cujipers, Carlbring, Messer & Fuller-Tyszkiewicz, 2019). Notably, the efficacy of lifestyle intervention using booklets and app have not been compared. This pilot study can inform the field about the efficacy of lifestyle intervention using two self-help delivery modalities and offer new ways to better managing depressive symptoms. This study will be a randomised controlled trial comparing self-help LM delivered by a smartphone app and booklets in improving depression. For a pilot study, a sample size of 12 per group is recommended (Julious, 2005). Considering an estimation of 20% attrition at the three assessment time points, the final sample size is 90, with 30 participants in each group. The LM booklet group will receive a pocket size 6-page booklet weekly that covers 8 lifestyle medicine themes including stress, relaxation, diet, exercise, sleep hygiene, worry management, mindfulness, and positive psychology. Exercises based on cognitive behavioural therapy and guidance to set and meet short term and long-term goals are featured in the booklets. The booklet series is reviewed by a panel of experts including clinical psychologists, psychiatrists, dietitians, physical trainers, and traditional Chinese Medicine practitioners. The app group will receive access to a mobile app that offers 8 modules with identical content as the wellness booklets, in addition to videos, relaxation, exercise and cooking demonstrations, daily challenges and record of goals. The waitlist control group will receive access to the app and booklets at the end of the study.
Official Title
-----------------
A Comparison of Self-help Lifestyle Modification Delivered by a Smartphone App and Booklets in Managing Depressive Symptoms: a Pilot Randomised Controlled Trial.
Conditions
-----------------
Depression
Intervention / Treatment
-----------------
* Other: Lifestyle medicine smartphone booklets
* Other: Lifestyle medicine smartphone app
* Other: Waitlist control
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants with elevated depressive symptoms as defined by PHQ-9 score 10 or above Hong Kong residents Aged 18 or above Able to read Chinese and type in Chinese or English Have an Internet-enabled mobile device (iOS or Android operating system) Exclusion Criteria: Pregnancy; Using medication or psychotherapy for depression; Currently participating in other psychological intervention studies; Cognitive impairment; Having unsafe conditions and are not recommended for physical activity or a change in diet by physicians; Self-disclosure of any major psychiatric, medical, or neurocognitive disorders that make participation unsuitable or may interfere with the adherence of the lifestyle modification; Any suicidal ideation (scoring above 2 in item 9 in BDI-II) Participants with any urgent health necessity were excluded and referred.
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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lifestyle medicine smartphone app<br>The app group will receive an app to facilitate lifestyle modification such as video demonstrations of physical activity, diet recommendations, stress and sleep management. | Other: Lifestyle medicine smartphone app<br>* The lifestyle medicine app offers 8 modules with identical content as the wellness booklets, in addition to videos, relaxation, exercise and cooking demonstrations, daily challenges, record of goals, and ecological momentary assessments of diet, physical activity, sleep, stress and mood.<br>|
| Experimental: lifestyle medicine booklets<br>The booklet group will receive 8 lifestyle medicine and psychoeducation booklets with identical content with the lifestyle medicine app. | Other: Lifestyle medicine smartphone booklets<br>* Participants will receive a pocket size 6-page booklet weekly over 8 weeks that covers 8 lifestyle medicine, mental health and CBT themes including stress, relaxation, diet, exercise, sleep hygiene, worry management, mindfulness, and positive psychology, and guides participants to set and meet short term and long-term goals.<br>|
| Sham Comparator: waitlist control<br>The waitlist control group will receive access to the lifestyle medicine app and booklets at the end of the study. | Other: Waitlist control<br>* The waitlist control group will receive access to the lifestyle medicine app and booklets at the end of the study.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Patient Health Questionnaire (PHQ-9) | The PHQ-9, a 20-item questionnaire used for screening, diagnosing, monitoring and measuring the severity of depression, which scores each of the nine DSM-IV criteria as 0 (not at all) to 3 (nearly every day). | baseline, immediately post-intervention, 4-week and 12-week follow-up |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-developed survey | A self-developed survey will collect information including demographic information (e.g., age, gender, level of education, working industry, relationship status, and location of residence), substance use, body mass index (BMI), rest-activity pattern, and social rhythms, etc. | Baseline |
| Change in the World Health Organization 5-item Well-Being Index | This is a 5-item measure of global subjective well-being. The internal consistency prior to treatment was 0.86. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Short Form (Six-Dimension) Health Survey (SF-6D) | SF-6D is a preference-based single index measure of health. A six-digit number represents each SF-6D health state, each digit denotes the level of one of six SF-6D dimensions: physical functioning, role limitation, social functioning, bodily pain, mental health, and vitality. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Perceived Stress Scale (PSS) | The PSS measures the perceived amount of stress experienced over the past month. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Generalized Anxiety Disorder 7-Item Scale (GAD-7) | The GAD-7, a 7-item questionnaire used for screening, diagnosing, monitoring and measuring the severity of anxiety over the past two weeks on a 4-point scale, 0 (not at all) to 4 (nearly every day). | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Sheehan Disability Scale (SDS) | SDS is a brief, 5-item self-report tool that assesses functional impairment in work/school, social life, and family life. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Health-Promoting Lifestyle Profile (HPLP II) | The 52-item HPLPII is composed of a total scale and six subscales to measure behaviors in the theorized dimensions of health-promoting lifestyle: spiritual growth, interpersonal relations, nutrition, physical activity, health responsibility, and stress management. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the International Physical Activities Questionnaire - Chinese version (IPAQ-C) | Participants' sitting time, walking time and moderate and vigorous physical activity are assessed by 5 questions from the short form of the International Physical Activity Questionnaire - Chinese version. Participants' engagement in brief strength and stamina-enhancing activity were assessed by asking the number of days they engaged in physical activity while seated and standing in the last seven days. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
| Change in the Insomnia Severity Index (ISI) | The ISI is a 7-item scale designed to evaluate perceived insomnia severity. Ratings on the 5-point Likert scale are obtained on the perceived severity of sleep-onset, sleep-maintenance, early morning awakening problems, satisfaction with current sleep pattern, interference with daily functioning, noticeably of impairment attributed to the sleep problem, and level of distress caused by the sleep problem. | baseline, immediately post-intervention, 4-week and 12-week follow-up |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Depression, Self-help, Lifestyle Medicine, Well-being
|
NCT02895802
|
Assessing the Feasibility of the Use of Visual Aids in Patient Education in Adults With Down Syndrome (DS)
|
Purpose: To assess the feasibility of using videos depicting people with DS to teach other adults with DS to perform healthy behaviors.~Hypothesis: Videos of adults with DS performing healthy behaviors is a more effective way to promote healthy behaviors by adults with DS than other methods tested.~This project will study whether videos showing a person with DS washing his hands correctly can improve hand washing by other adults with DS.
|
The subjects will be recruited and identified and consented. Subjects will be randomized to one of 4 groups.~i. Verbal instructions on hand washing with pictures (using the Illinois department of public health tools) ii. Verbal instructions on hand washing and video of the ADSC iii. Verbal instructions on hand washing and video of an adult without DS washing his hands iv. Verbal instructions on hand washing and video of an adult with DS washing his hands.~Videos of the handwashing process will be taken pre intervention and then again post intervention.~Scoring assessments will be completed upon review of the 2 files by 2 separate study team members, the second of which will be blinded to the information they will be reviewing.
|
Assessing the Feasibility of the Use of Visual Aids in Patient Education in Adults With Down Syndrome (DS)
|
Down Syndrome
|
* Behavioral: Verbal instructions with picture diagram
* Behavioral: Verbal instructions with video of ADSC
* Behavioral: verbal instructions w. video of w/o DS
* Behavioral: verbal instructions w. video w/DS
|
Inclusion Criteria:~People with Down syndrome receiving care at Advocate~No known sensitivity to soap~Exclusion Criteria:~Pregnant women, prisoners~Known sensitivity to soap
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score on handwashing checklist | 2 minute videos will be reviewed and scored twice. First by research coordinator then by blinded reviewer. Scores will be compared and reported. | 2 minutes |
|
down syndrome
|
Down Syndrome, Syndrome, Disease, Pathologic Processes, Intellectual Disability, Neurobehavioral Manifestations, Neurologic Manifestations, Nervous System Diseases, Abnormalities, Multiple, Congenital Abnormalities, Chromosome Disorders, Genetic Diseases, Inborn
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Verbal instructions with picture diagram<br>hand washing is scored prior and after educational intervention with verbal instructions of handwashing and a picture diagram of handwashing. | Behavioral: Verbal instructions with picture diagram<br>* verbal instructions and picture diagram<br>|
| Other: Verbal instructions with video of ADSC<br>hand washing is scored prior and after educational intervention with verbal instructions of handwashing and a video of the adult down syndrome center | Behavioral: Verbal instructions with video of ADSC<br>* Verbal instructions and watching video depicting ADSC<br>|
| Other: verbal instructions w. video of w/o DS<br>hand washing is scored prior and after educational intervention with verbal instructions of handwashing and viewing an educational video depicting a person without down syndrome washing their hands. | Behavioral: verbal instructions w. video of w/o DS<br>* verbal instructions and watching video depicting person without DS washing her hands<br>|
| Other: verbal instructions w.video w/DS<br>hand washing is scored prior and after educational intervention with verbal instructions of handwashing and watching an educational video depicting a person with down syndrome washing their hands. | Behavioral: verbal instructions w. video w/DS<br>* verbal instructions and watching video depicting person with DS washing his hands<br>|
|
Assessing the Feasibility of the Use of Visual Aids in Patient Education in Adults With Down Syndrome (DS)
Study Overview
=================
Brief Summary
-----------------
Purpose: To assess the feasibility of using videos depicting people with DS to teach other adults with DS to perform healthy behaviors. Hypothesis: Videos of adults with DS performing healthy behaviors is a more effective way to promote healthy behaviors by adults with DS than other methods tested. This project will study whether videos showing a person with DS washing his hands correctly can improve hand washing by other adults with DS.
Detailed Description
-----------------
The subjects will be recruited and identified and consented. Subjects will be randomized to one of 4 groups. i. Verbal instructions on hand washing with pictures (using the Illinois department of public health tools) ii. Verbal instructions on hand washing and video of the ADSC iii. Verbal instructions on hand washing and video of an adult without DS washing his hands iv. Verbal instructions on hand washing and video of an adult with DS washing his hands. Videos of the handwashing process will be taken pre intervention and then again post intervention. Scoring assessments will be completed upon review of the 2 files by 2 separate study team members, the second of which will be blinded to the information they will be reviewing.
Official Title
-----------------
Assessing the Feasibility of the Use of Visual Aids in Patient Education in Adults With Down Syndrome (DS)
Conditions
-----------------
Down Syndrome
Intervention / Treatment
-----------------
* Behavioral: Verbal instructions with picture diagram
* Behavioral: Verbal instructions with video of ADSC
* Behavioral: verbal instructions w. video of w/o DS
* Behavioral: verbal instructions w. video w/DS
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: People with Down syndrome receiving care at Advocate No known sensitivity to soap Exclusion Criteria: Pregnant women, prisoners Known sensitivity to soap
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: Health Services Research
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Verbal instructions with picture diagram<br>hand washing is scored prior and after educational intervention with verbal instructions of handwashing and a picture diagram of handwashing. | Behavioral: Verbal instructions with picture diagram<br>* verbal instructions and picture diagram<br>|
| Other: Verbal instructions with video of ADSC<br>hand washing is scored prior and after educational intervention with verbal instructions of handwashing and a video of the adult down syndrome center | Behavioral: Verbal instructions with video of ADSC<br>* Verbal instructions and watching video depicting ADSC<br>|
| Other: verbal instructions w. video of w/o DS<br>hand washing is scored prior and after educational intervention with verbal instructions of handwashing and viewing an educational video depicting a person without down syndrome washing their hands. | Behavioral: verbal instructions w. video of w/o DS<br>* verbal instructions and watching video depicting person without DS washing her hands<br>|
| Other: verbal instructions w.video w/DS<br>hand washing is scored prior and after educational intervention with verbal instructions of handwashing and watching an educational video depicting a person with down syndrome washing their hands. | Behavioral: verbal instructions w. video w/DS<br>* verbal instructions and watching video depicting person with DS washing his hands<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score on handwashing checklist | 2 minute videos will be reviewed and scored twice. First by research coordinator then by blinded reviewer. Scores will be compared and reported. | 2 minutes |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
down syndrome
|
|
NCT00427180
|
IRIS PILOT - Extended Pilot Study With a Retinal Implant System
|
Investigate whether blind subjects that fulfil the patient criteria provided with a Retinal Implant are able to differentiate between simple patterns like horizontal bar, vertical bar and cross.
|
The Retinal Implant System consists of three main components, the Retinal Stimulator, which is the component actually implanted into the eye, the visual interface, and the Pocket Processor The Retinal Stimulator will be implanted into the eye of a blind subject during a surgical operation. However, the external components are activated only during the test sessions under the control of the investigator team. In a first step of the investigation a software controlled system on a PC which is connected to the Pocket Processor via Ethernet interface, will generate the defined stimulation patterns (bars, crosses, cubes). During the test session, the blind subject is exposed to a series of these stimulation patterns and he / she has to describe the visual perceptions. Based on his descriptions and in an interactive way, the stimulation signal is subsequently be modulated by changing parameters like amplitude, duration of impulse, polarity, number of repetitions or pulse frequency on the PC.~In a second step the visual interface is equipped with a camera which presents realtime images to the subject. Data obtained from the investigation with computer generated patterns in the first step are used in the second step to improve the fitting software for the use in the camera supported system.~Finally the system should enable the subject to recognize simple images supported from the camera.
|
Extended Pilot Study to Evaluate Pattern Recognition With a Chronic Retinal Implant System
|
Retinitis Pigmentosa, Cone-Rod Dystrophy, Choroideremia
|
* Device: Retinal Implant System (IRIS)
|
Inclusion Criteria~Age between 30 and 79 years at the date of enrollment~Normal hearing and linguistic understanding (with hearing aids if - necessary and in the language of the hospital or in English)~Ability to understand the study and procedures involved~Willingness to participate and comply with follow-up procedures~Good general health based on investigator's opinion~Ability to undergo surgery using general anaesthesia~Signed informed consent~RP, choroideremia, or rod cone dystrophy~Visual field less than 40 ° (if measurable)~Visual acuity not better than (1/50), (logMAR≥1.7)~Visual function stable for a duration of at least one year (according to subject statement)~Normal eye pressure (9-21 mmHg)~Bulbus length (AP) between 21 and 25 mm~Exclusion Criteria~Allergic response to multiple antibiotics~Known allergies to materials of the implant~Known carrier of multi-resistant organisms~Pregnancy or lactating~History of epileptic seizures~Having active implantable devices (or need within the next 3 years)~Patients with cancer or patients received cancer therapy within the last 2 years~Currently undergoing psychiatric treatment without expert opinion approving participation on the study~Patients having insufficient mental capacity~Neurological diseases, in particular those affecting nerve conduction velocities~Patients currently taking medications affecting brain function~Immunosuppressive subjects
|
30 Years
|
79 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate whether blind subjects that fulfill the patient criteria provided with a Retinal Implant are able to differentiate between simple patterns like horizontal bar, vertical bar and cross. | | 18 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary goals of this study phase are: Further evaluation of stimulation parameters, Light localization with use of camera, Safety verification of stimulation parameters | | 18 months |
|
Visual Perception, Retina, Light, Retinitis Pigmentosa, Visual acuity, Retinal Implant, Electrical stimulation
|
Retinitis, Retinitis Pigmentosa, Choroideremia, Cone-Rod Dystrophies, Retinal Diseases, Eye Diseases, Eye Diseases, Hereditary, Retinal Dystrophies, Retinal Degeneration, Genetic Diseases, Inborn, Choroid Diseases, Uveal Diseases, Genetic Diseases, X-Linked
|
| Intervention/Treatment |
| --- |
|Device: Retinal Implant System (IRIS)|AIMD - Active Implantable Medical Device designed for artificial electrical neural stimulation of photoreceptor degenerated retina|
|
IRIS PILOT - Extended Pilot Study With a Retinal Implant System
Study Overview
=================
Brief Summary
-----------------
Investigate whether blind subjects that fulfil the patient criteria provided with a Retinal Implant are able to differentiate between simple patterns like horizontal bar, vertical bar and cross.
Detailed Description
-----------------
The Retinal Implant System consists of three main components, the Retinal Stimulator, which is the component actually implanted into the eye, the visual interface, and the Pocket Processor The Retinal Stimulator will be implanted into the eye of a blind subject during a surgical operation. However, the external components are activated only during the test sessions under the control of the investigator team. In a first step of the investigation a software controlled system on a PC which is connected to the Pocket Processor via Ethernet interface, will generate the defined stimulation patterns (bars, crosses, cubes). During the test session, the blind subject is exposed to a series of these stimulation patterns and he / she has to describe the visual perceptions. Based on his descriptions and in an interactive way, the stimulation signal is subsequently be modulated by changing parameters like amplitude, duration of impulse, polarity, number of repetitions or pulse frequency on the PC. In a second step the visual interface is equipped with a camera which presents realtime images to the subject. Data obtained from the investigation with computer generated patterns in the first step are used in the second step to improve the fitting software for the use in the camera supported system. Finally the system should enable the subject to recognize simple images supported from the camera.
Official Title
-----------------
Extended Pilot Study to Evaluate Pattern Recognition With a Chronic Retinal Implant System
Conditions
-----------------
Retinitis Pigmentosa, Cone-Rod Dystrophy, Choroideremia
Intervention / Treatment
-----------------
* Device: Retinal Implant System (IRIS)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Age between 30 and 79 years at the date of enrollment Normal hearing and linguistic understanding (with hearing aids if - necessary and in the language of the hospital or in English) Ability to understand the study and procedures involved Willingness to participate and comply with follow-up procedures Good general health based on investigator's opinion Ability to undergo surgery using general anaesthesia Signed informed consent RP, choroideremia, or rod cone dystrophy Visual field less than 40 ° (if measurable) Visual acuity not better than (1/50), (logMAR≥1.7) Visual function stable for a duration of at least one year (according to subject statement) Normal eye pressure (9-21 mmHg) Bulbus length (AP) between 21 and 25 mm Exclusion Criteria Allergic response to multiple antibiotics Known allergies to materials of the implant Known carrier of multi-resistant organisms Pregnancy or lactating History of epileptic seizures Having active implantable devices (or need within the next 3 years) Patients with cancer or patients received cancer therapy within the last 2 years Currently undergoing psychiatric treatment without expert opinion approving participation on the study Patients having insufficient mental capacity Neurological diseases, in particular those affecting nerve conduction velocities Patients currently taking medications affecting brain function Immunosuppressive subjects
Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 79 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: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Intervention/Treatment |
| --- |
|Device: Retinal Implant System (IRIS)|AIMD - Active Implantable Medical Device designed for artificial electrical neural stimulation of photoreceptor degenerated retina|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate whether blind subjects that fulfill the patient criteria provided with a Retinal Implant are able to differentiate between simple patterns like horizontal bar, vertical bar and cross. | | 18 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary goals of this study phase are: Further evaluation of stimulation parameters, Light localization with use of camera, Safety verification of stimulation parameters | | 18 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Visual Perception, Retina, Light, Retinitis Pigmentosa, Visual acuity, Retinal Implant, Electrical stimulation
|
NCT04009408
|
Expiratory Muscle Strength Training (EMST) in Neuromuscular Disorders
|
The purpose of this study is to investigate the impact of expiratory muscle strength training (EMST) on the swallowing, breathing, oral intake, quality of life and cough function of people with oculopharyngeal muscular dystrophy (OPMD).
|
Outline:~Twenty participants with OPMD, with dysphagia, will be recruited from Neuromuscular clinics within Calgary. The investigators will enrol patients in a parallel group, sham-controlled, randomized clinical trial, with 10 participants in each group (active EMST and sham EMST).~Participants will have baseline measurements of: (i) global swallowing function via modified barium swallow study, (ii) maximum expiratory pressure, (iii) voluntary cough spirometry, (iv) forced vital capacity, (v) functional oral intake, (vi) patient report of self-perceived swallowing impairment (EAT-10 Questionnaire), and (vii) biomarker analyses.~Participants will undergo 5-weeks of EMST (active or sham). All baseline measurements will be repeated after 5-weeks of EMST and 10-weeks post-EMST to measure durability of effect.~Outcomes:~The end-goal of the current research is to obtain preliminary data for the benefit of EMST in a new study population, and direct future studies that may provide evidence for a new standard of care in treating neuromuscular diagnoses.
|
Interventional Study of Expiratory Muscle Strength Training as a Treatment in Neuromuscular Disorders
|
Oculopharyngeal Muscular Dystrophy, Muscular Dystrophies, Myopathy; Hereditary
|
* Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)
|
Inclusion Criteria:~Diagnosis of oculopharyngeal muscular dystrophy (OPMD)~18 years of age or older~Must be capable of providing informed consent~Must be able to undergo respiratory function testing and swallowing studies~Must have a forced vital capacity (FVC) greater than 60%~A score of 3 or greater on the Eating Assessment Tool-10 (EAT-10; self-administered, symptom-specific outcome instrument for dysphagia. A score of 3 or greater indicates increased stress around eating)~A score of 26 or greater on the Montreal Cognitive Assessment (MoCA; 30-point screening assessment used for detecting cognitive impairment. A score of 26 or greater is considered to be within functional limits.)~Exclusion Criteria:~Severe coronary artery disease~Acute myocardial infarction~Moderate to severe hypovolemia~Acute neurological events~Unstable cardiac status~Recent hernia~Severe chronic obstructive pulmonary disease (COPD)~Uncontrolled reflux issues~Women who are pregnant, or who suspect they may be pregnant~Cognitive impairment that would prevent comprehension of instructions and adherence to intervention guidelines (a score of less than 26 points on the MoCA)
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel group, double blind, sham controlled study
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Swallowing Function | Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening. A lower score is a better outcome. | Change in score from week 0 to week 5 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Swallowing Function | Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening. | Change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Maximum expiratory pressure (MEP) | MEP is a measure of respiratory muscle strength and is assessed with a handheld manometer, measured in centimetres of water (cmH2O). A higher score is a better outcome. | Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Volitional cough strength (peak cough flow) | Measure of cough strength that is assessed using a spirometer, measured in litres per minute (L/min). A higher score is a better outcome. | Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Forced vital capacity (FVC) | Measure of how much air is exhaled during forced exhalation and is assessed with a spirometer, measured in litres. A higher score is a better outcome. | Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Oral Intake | A measure daily nutritional and hydration consumption. Oral intake is assessed using the Functional Oral Intake Scale (FOIS), a validated 7-point ordinal scale (1 = no oral intake; 2 = tube dependent with minimal/inconsistent oral intake; 3 = tube supplements with consistent oral intake; 4 = total oral intake in single consistency; 5 = total oral intake of multiple consistencies requiring special preparation; 6 = total oral intake with no special preparation, but must avoid specific foods or liquid items; 7 = total oral intake with no restrictions). A higher score is a better outcome. | Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Self-perceived swallowing impairment | Will be measured using the Eating Assessment Tool-10 (EAT-10), a self-administered, symptom-specific outcome instrument for dysphagia. The EAT-10 allows patients to rate their swallowing symptoms on scale of 0 = no problem to 4 = severe problem. A lower score is a better outcome. | Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Biomarker analyses | An optional blood sample will be collected for biomarker analysis, to identify correlations with clinical response. We will measure genetic biomarkers associated with swallowing function including rs6265, rs165599, rs10835211, rs17601696, and APOE4 genotype status. For these 5 genetic biomarkers, participants will be scored as having zero, one, or two alleles. This information will be used in subgroup analyses for the primary and secondary outcomes. | Baseline measurement (week 0) |
|
Dysphagia, Myopathy, Muscular Dystrophy
|
Muscular Dystrophies, Muscular Diseases, Muscular Dystrophy, Oculopharyngeal, Neuromuscular Diseases, Muscular Disorders, Atrophic, Musculoskeletal Diseases, Nervous System Diseases, Genetic Diseases, Inborn
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EMST therapy<br>Participants use the EMST device as per study protocol, set to 50% of the patient's maximal expiratory pressure, as measured by handheld manometer. | Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)<br>* Active therapy calibrated to the participant's maximum expiratory pressure<br>|
| Sham Comparator: Sham EMST therapy<br>Participants use a sham EMST device that has the spring removed as per study protocol, with no significant airflow resistance. | Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)<br>* Active therapy calibrated to the participant's maximum expiratory pressure<br>|
|
Expiratory Muscle Strength Training (EMST) in Neuromuscular Disorders
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the impact of expiratory muscle strength training (EMST) on the swallowing, breathing, oral intake, quality of life and cough function of people with oculopharyngeal muscular dystrophy (OPMD).
Detailed Description
-----------------
Outline: Twenty participants with OPMD, with dysphagia, will be recruited from Neuromuscular clinics within Calgary. The investigators will enrol patients in a parallel group, sham-controlled, randomized clinical trial, with 10 participants in each group (active EMST and sham EMST). Participants will have baseline measurements of: (i) global swallowing function via modified barium swallow study, (ii) maximum expiratory pressure, (iii) voluntary cough spirometry, (iv) forced vital capacity, (v) functional oral intake, (vi) patient report of self-perceived swallowing impairment (EAT-10 Questionnaire), and (vii) biomarker analyses. Participants will undergo 5-weeks of EMST (active or sham). All baseline measurements will be repeated after 5-weeks of EMST and 10-weeks post-EMST to measure durability of effect. Outcomes: The end-goal of the current research is to obtain preliminary data for the benefit of EMST in a new study population, and direct future studies that may provide evidence for a new standard of care in treating neuromuscular diagnoses.
Official Title
-----------------
Interventional Study of Expiratory Muscle Strength Training as a Treatment in Neuromuscular Disorders
Conditions
-----------------
Oculopharyngeal Muscular Dystrophy, Muscular Dystrophies, Myopathy; Hereditary
Intervention / Treatment
-----------------
* Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of oculopharyngeal muscular dystrophy (OPMD) 18 years of age or older Must be capable of providing informed consent Must be able to undergo respiratory function testing and swallowing studies Must have a forced vital capacity (FVC) greater than 60% A score of 3 or greater on the Eating Assessment Tool-10 (EAT-10; self-administered, symptom-specific outcome instrument for dysphagia. A score of 3 or greater indicates increased stress around eating) A score of 26 or greater on the Montreal Cognitive Assessment (MoCA; 30-point screening assessment used for detecting cognitive impairment. A score of 26 or greater is considered to be within functional limits.) Exclusion Criteria: Severe coronary artery disease Acute myocardial infarction Moderate to severe hypovolemia Acute neurological events Unstable cardiac status Recent hernia Severe chronic obstructive pulmonary disease (COPD) Uncontrolled reflux issues Women who are pregnant, or who suspect they may be pregnant Cognitive impairment that would prevent comprehension of instructions and adherence to intervention guidelines (a score of less than 26 points on the MoCA)
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: Parallel group, double blind, sham controlled study
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EMST therapy<br>Participants use the EMST device as per study protocol, set to 50% of the patient's maximal expiratory pressure, as measured by handheld manometer. | Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)<br>* Active therapy calibrated to the participant's maximum expiratory pressure<br>|
| Sham Comparator: Sham EMST therapy<br>Participants use a sham EMST device that has the spring removed as per study protocol, with no significant airflow resistance. | Device: Expiratory muscle strength therapy (EMST150, Aspire LLC)<br>* Active therapy calibrated to the participant's maximum expiratory pressure<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Swallowing Function | Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening. A lower score is a better outcome. | Change in score from week 0 to week 5 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Swallowing Function | Global swallowing function is rated from videofluoroscopy swallowing studies (VFSS), using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), a validated 5-point scale. Global swallowing function is rated from 0-4: 0 = no pharyngeal dysphagia; 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening. | Change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Maximum expiratory pressure (MEP) | MEP is a measure of respiratory muscle strength and is assessed with a handheld manometer, measured in centimetres of water (cmH2O). A higher score is a better outcome. | Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Volitional cough strength (peak cough flow) | Measure of cough strength that is assessed using a spirometer, measured in litres per minute (L/min). A higher score is a better outcome. | Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Forced vital capacity (FVC) | Measure of how much air is exhaled during forced exhalation and is assessed with a spirometer, measured in litres. A higher score is a better outcome. | Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Oral Intake | A measure daily nutritional and hydration consumption. Oral intake is assessed using the Functional Oral Intake Scale (FOIS), a validated 7-point ordinal scale (1 = no oral intake; 2 = tube dependent with minimal/inconsistent oral intake; 3 = tube supplements with consistent oral intake; 4 = total oral intake in single consistency; 5 = total oral intake of multiple consistencies requiring special preparation; 6 = total oral intake with no special preparation, but must avoid specific foods or liquid items; 7 = total oral intake with no restrictions). A higher score is a better outcome. | Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Self-perceived swallowing impairment | Will be measured using the Eating Assessment Tool-10 (EAT-10), a self-administered, symptom-specific outcome instrument for dysphagia. The EAT-10 allows patients to rate their swallowing symptoms on scale of 0 = no problem to 4 = severe problem. A lower score is a better outcome. | Change in score from week 0 to week 5; change in score from week 0 to week 15; change in score from week 5 to week 15. |
| Biomarker analyses | An optional blood sample will be collected for biomarker analysis, to identify correlations with clinical response. We will measure genetic biomarkers associated with swallowing function including rs6265, rs165599, rs10835211, rs17601696, and APOE4 genotype status. For these 5 genetic biomarkers, participants will be scored as having zero, one, or two alleles. This information will be used in subgroup analyses for the primary and secondary outcomes. | Baseline measurement (week 0) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dysphagia, Myopathy, Muscular Dystrophy
|
NCT02918188
|
Therapeutic Effects of Hydrogen on Steroid-refractory/or Steroid-dependent cGVHD
|
This study suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD.
|
The investigators will evaluate clinical response rate, time to treatment Failure (TTF), overall survival (OS), and toxicity in cGVHD patients.
|
Therapeutic Effects of Hydrogen on Steroid-refractory/or Steroid-dependent Chronic Graft-versus-host-disease
|
Chronic Graft-versus-host Disease
|
* Drug: Hydrogen
|
Inclusion Criteria:~Written informed consent~Male~not pregnant female~patients <65 years old~Diagnosis of cGVHD steroid refractory (no response after Prednisone ≥1mg/kg ) or steroid-dependent cGVHD (had an initial response followed by a cGVHD flare upon steroid taper)~Patient intolerant to steroid therapy~Exclusion Criteria:~Patients with stable disease, not well controlled by the current treatment~Pregnancy~HIV positive~Severe liver or renal impairment: serum creatinine >2.5 mg/dl; serum bilirubin>2.5 mg/dl (without evidence of hepatic cGVHD)~Uncontrolled malignancies including the persistence of the underlying malignancy before the Allogeneic Transplantation and the relapse of hematopoietic malignancy~Any other investigational agents administered within last four weeks~Cardiac insufficiency (>grade II, New York Heart Association classification)~Inability to comply with medical therapy or follow-up
| null |
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall Response Rate (ORR) is defined as an Objective improvement at sixth month, and includes at least 1 of the following criteria:~At least 50% reduction of body surface area involved; Reduction (at least 20%) of skin sclerosis, measured by Rodnan score Improvement>1 point in functional pulmonary tests, evaluated by LFS score; >50% steroid reduction (for at least 4 weeks) | 12 months after date of start of Hydrogen |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate in each domain (RRD) | Response rate in each domain was measured in subjects that had had initial involvement in that domain | 12 months after date of start of Hydrogen |
|
Bronchiolitis Obliterans Syndrome, Graft vs Host Disease, Immune System Diseases, Organizing Pneumonia, Bronchiolitis Obliterans, Bronchiolitis, Bronchitis, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive, Lung Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydrogen<br>Patients will receive hydrogen-rich water (4mL/kg three times one day, 0.8 ppm) | Drug: Hydrogen<br>* Patients will receive hydrogen-rich water orally (500mL three times one day, 0.6mM)<br>* Other names: Hydrogen-rich water;|
|
Therapeutic Effects of Hydrogen on Steroid-refractory/or Steroid-dependent cGVHD
Study Overview
=================
Brief Summary
-----------------
This study suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD.
Detailed Description
-----------------
The investigators will evaluate clinical response rate, time to treatment Failure (TTF), overall survival (OS), and toxicity in cGVHD patients.
Official Title
-----------------
Therapeutic Effects of Hydrogen on Steroid-refractory/or Steroid-dependent Chronic Graft-versus-host-disease
Conditions
-----------------
Chronic Graft-versus-host Disease
Intervention / Treatment
-----------------
* Drug: Hydrogen
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Male not pregnant female patients <65 years old Diagnosis of cGVHD steroid refractory (no response after Prednisone ≥1mg/kg ) or steroid-dependent cGVHD (had an initial response followed by a cGVHD flare upon steroid taper) Patient intolerant to steroid therapy Exclusion Criteria: Patients with stable disease, not well controlled by the current treatment Pregnancy HIV positive Severe liver or renal impairment: serum creatinine >2.5 mg/dl; serum bilirubin>2.5 mg/dl (without evidence of hepatic cGVHD) Uncontrolled malignancies including the persistence of the underlying malignancy before the Allogeneic Transplantation and the relapse of hematopoietic malignancy Any other investigational agents administered within last four weeks Cardiac insufficiency (>grade II, New York Heart Association classification) Inability to comply with medical therapy or follow-up
Ages Eligible for Study
-----------------
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 |
| --- | --- |
| Experimental: Hydrogen<br>Patients will receive hydrogen-rich water (4mL/kg three times one day, 0.8 ppm) | Drug: Hydrogen<br>* Patients will receive hydrogen-rich water orally (500mL three times one day, 0.6mM)<br>* Other names: Hydrogen-rich water;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall Response Rate (ORR) is defined as an Objective improvement at sixth month, and includes at least 1 of the following criteria: At least 50% reduction of body surface area involved; Reduction (at least 20%) of skin sclerosis, measured by Rodnan score Improvement>1 point in functional pulmonary tests, evaluated by LFS score; >50% steroid reduction (for at least 4 weeks) | 12 months after date of start of Hydrogen |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate in each domain (RRD) | Response rate in each domain was measured in subjects that had had initial involvement in that domain | 12 months after date of start of Hydrogen |
|
|
NCT00869245
|
Efficacy Evaluation of Observation Unit Cardiac Magnetic Resonance Imaging (MRI) in Patients With Intermediate Risk Acute Chest Pain
|
The purpose of this study is to investigate the best way to evaluate patients with chest pain in the emergency department. It compares types of cardiac tests performed while receiving treatment in an observation unit. Patients will either undergo cardiac MRI testing or conventional care testing. Patients treated in the conventional care testing group will undergo the testing their doctor determines is best for them. All patients will undergo follow up to find out if they have had any heart related events.
|
Despite spending $12 billion annually on the emergency evaluation of chest pain in the US, only 15% of admitted patients have a cardiac cause of their presenting symptoms. Observation units (OU) improve resource utilization, are endorsed by the ACC/AHA guidelines, but have seen limited implementation in non-low risk chest pain patients due to limitations of traditional cardiac testing. Cardiac magnetic resonance imaging (CMR) is sensitive and specific for ischemia, can simultaneously assess cardiac function and myocardial perfusion, and could revolutionize the diagnostic process for intermediate risk patients with chest pain. The superior accuracy of CMR could decrease testing resulting from false positive results. The high sensitivity for ongoing ischemia could allow imaging in parallel with cardiac markers.~Research hypotheses:~OU-CMR will have superior therapeutic efficacy to OU-conventional testing.~An OU-CMR strategy will have higher diagnostic thinking efficacy than OU-conventional testing.~Methods summary:~To address the question of feasibility of a CMR approach to managing patients at intermediate risk for ACS, we propose a randomized clinical trial of 120 patients at intermediate risk of ACS that present to the ED of Wake Forest University Baptist Medical Center (WFUBMC) for evaluation of chest pain. All patients will receive care in an OU, and will be randomized to CMR, or conventional testing. CMR participants will undergo cardiac markers and CMR testing; conventional testing participants will undergo serial cardiac markers followed by conventional cardiac testing. ACS (infarction, death, coronary revascularization, unstable angina) will be assessed by evaluation of hospital course and phone follow-up at 30 days. Cost of hospital care will be compared among groups.
|
Efficacy Evaluation of Observation Unit Cardiac Magnetic Resonance Imaging (MRI) in Patients With Intermediate Risk Acute Chest Pain
|
Acute Coronary Syndrome, Chest Pain
|
* Other: OU - Cardiac MRI
* Other: OU - Conventional Care Testing
|
Inclusion Criteria:~Age greater than or equal to 18 years~Chest discomfort or other symptoms consistent with possible ACS~TIMI risk score ≥ 1 or physician impression* of intermediate or high likelihood symptoms represent ACS~Patient requires an inpatient or observation unit evaluation for their chest pain~The treating physician feels the patient could be discharged home if cardiac disease was excluded~ED attending feels patient is safe for observation unit care**~Exclusion Criteria:~Initial troponin I > 1.0 ng/ml~New ST-segment elevation (≥1mV) or depression (≥2 mV)~Contra-indications to MRI (listed below)~Unable to lie flat~Hypotension (systolic < 90 mm Hg)~Renal insufficiency (estimated GFR < 45 cc/min) or end stage renal disease~Life expectancy less than 3 months~Patient refusal of medical record review and follow-up at 30 days~Pregnancy~Liver, heart, or kidney transplant~Chronic liver disease~Unable to speak English or Spanish~The ED attending feels that cardiac catheterization is indicated~The ED care provider intends to order a CT coronary angiogram~(*)Physicians are encouraged to use the 2007 ACC/AHA guidelines for the management of patients with NSTE ACS as a framework for this assessment.(1)~(**)These patients should generally not be considered for observation unit care: PCI / CAGB in past 6 months, multiple stents, multiple prior MIs~Contraindications to MRI: (Pacemaker, defibrillator, cerebral aneurysm clips, metallic ocular foreign body, implanted devices, claustrophobia)
|
18 Years
| null |
All
|
No
|
Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic efficacy: Length of stay | | Duration of Initial Hospitalization |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic efficacy: Correct cardiovascular admission decision | | Duration of Initial Hospitalization |
| Therapeutic efficacy: Non-therapeutic cardiac catheterizations | | 30 days |
| Diagnostic thinking efficacy: change in diagnostic certainty | | 30 days |
| Cost of index hospitalization | | Duration of Initial Hospitalization |
|
ACS, Acute Coronary Syndrome, Chest pain, Cardiac MRI, CMR, Risk Stratification, Emergency Department
|
Acute Coronary Syndrome, Chest Pain, Myocardial Ischemia, Heart Diseases, Cardiovascular Diseases, Vascular Diseases, Pain, Neurologic Manifestations
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Cardiac MRI Protocol. Patients will be transferred to the observation unit and undergo a stress cardiac MRI evaluation. | Other: OU - Cardiac MRI<br>* During ED evaluation, patients are randomized to cardiac MRI or conventional care testing.<br>|
| Experimental: 2<br>Conventional care cardiac testing. Patients will be transferred to the observation unit and undergo cardiac testing as determined by their treating physician. | Other: OU - Conventional Care Testing<br>* Patients in the conventional testing arm will undergo testing as determined by their treating physician.<br>|
|
Efficacy Evaluation of Observation Unit Cardiac Magnetic Resonance Imaging (MRI) in Patients With Intermediate Risk Acute Chest Pain
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the best way to evaluate patients with chest pain in the emergency department. It compares types of cardiac tests performed while receiving treatment in an observation unit. Patients will either undergo cardiac MRI testing or conventional care testing. Patients treated in the conventional care testing group will undergo the testing their doctor determines is best for them. All patients will undergo follow up to find out if they have had any heart related events.
Detailed Description
-----------------
Despite spending $12 billion annually on the emergency evaluation of chest pain in the US, only 15% of admitted patients have a cardiac cause of their presenting symptoms. Observation units (OU) improve resource utilization, are endorsed by the ACC/AHA guidelines, but have seen limited implementation in non-low risk chest pain patients due to limitations of traditional cardiac testing. Cardiac magnetic resonance imaging (CMR) is sensitive and specific for ischemia, can simultaneously assess cardiac function and myocardial perfusion, and could revolutionize the diagnostic process for intermediate risk patients with chest pain. The superior accuracy of CMR could decrease testing resulting from false positive results. The high sensitivity for ongoing ischemia could allow imaging in parallel with cardiac markers. Research hypotheses: OU-CMR will have superior therapeutic efficacy to OU-conventional testing. An OU-CMR strategy will have higher diagnostic thinking efficacy than OU-conventional testing. Methods summary: To address the question of feasibility of a CMR approach to managing patients at intermediate risk for ACS, we propose a randomized clinical trial of 120 patients at intermediate risk of ACS that present to the ED of Wake Forest University Baptist Medical Center (WFUBMC) for evaluation of chest pain. All patients will receive care in an OU, and will be randomized to CMR, or conventional testing. CMR participants will undergo cardiac markers and CMR testing; conventional testing participants will undergo serial cardiac markers followed by conventional cardiac testing. ACS (infarction, death, coronary revascularization, unstable angina) will be assessed by evaluation of hospital course and phone follow-up at 30 days. Cost of hospital care will be compared among groups.
Official Title
-----------------
Efficacy Evaluation of Observation Unit Cardiac Magnetic Resonance Imaging (MRI) in Patients With Intermediate Risk Acute Chest Pain
Conditions
-----------------
Acute Coronary Syndrome, Chest Pain
Intervention / Treatment
-----------------
* Other: OU - Cardiac MRI
* Other: OU - Conventional Care Testing
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age greater than or equal to 18 years Chest discomfort or other symptoms consistent with possible ACS TIMI risk score ≥ 1 or physician impression* of intermediate or high likelihood symptoms represent ACS Patient requires an inpatient or observation unit evaluation for their chest pain The treating physician feels the patient could be discharged home if cardiac disease was excluded ED attending feels patient is safe for observation unit care** Exclusion Criteria: Initial troponin I > 1.0 ng/ml New ST-segment elevation (≥1mV) or depression (≥2 mV) Contra-indications to MRI (listed below) Unable to lie flat Hypotension (systolic < 90 mm Hg) Renal insufficiency (estimated GFR < 45 cc/min) or end stage renal disease Life expectancy less than 3 months Patient refusal of medical record review and follow-up at 30 days Pregnancy Liver, heart, or kidney transplant Chronic liver disease Unable to speak English or Spanish The ED attending feels that cardiac catheterization is indicated The ED care provider intends to order a CT coronary angiogram (*)Physicians are encouraged to use the 2007 ACC/AHA guidelines for the management of patients with NSTE ACS as a framework for this assessment.(1) (**)These patients should generally not be considered for observation unit care: PCI / CAGB in past 6 months, multiple stents, multiple prior MIs Contraindications to MRI: (Pacemaker, defibrillator, cerebral aneurysm clips, metallic ocular foreign body, implanted devices, claustrophobia)
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: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Cardiac MRI Protocol. Patients will be transferred to the observation unit and undergo a stress cardiac MRI evaluation. | Other: OU - Cardiac MRI<br>* During ED evaluation, patients are randomized to cardiac MRI or conventional care testing.<br>|
| Experimental: 2<br>Conventional care cardiac testing. Patients will be transferred to the observation unit and undergo cardiac testing as determined by their treating physician. | Other: OU - Conventional Care Testing<br>* Patients in the conventional testing arm will undergo testing as determined by their treating physician.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic efficacy: Length of stay | | Duration of Initial Hospitalization |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic efficacy: Correct cardiovascular admission decision | | Duration of Initial Hospitalization |
| Therapeutic efficacy: Non-therapeutic cardiac catheterizations | | 30 days |
| Diagnostic thinking efficacy: change in diagnostic certainty | | 30 days |
| Cost of index hospitalization | | Duration of Initial Hospitalization |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ACS, Acute Coronary Syndrome, Chest pain, Cardiac MRI, CMR, Risk Stratification, Emergency Department
|
NCT02869295
|
A Phase 1/2 Multicenter Dose Escalation and Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumors
|
This is a first in human, open-label, sequential dose escalation and expansion Phase 1 study of NKTR-214 in adult patients with locally advanced or metastatic solid tumors.
|
An Open-Label, Multicenter, Dose Escalation And Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumor Malignancies
|
Unspecified Adult Solid Tumor, Protocol Specific
|
* Drug: NKTR-214
|
Inclusion Criteria:~Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor.~Received 1 or 2 prior lines of therapy.~Life expectancy >12 weeks.~Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.~Measurable disease per RECIST v1.1.~Demonstrated adequate organ function within 14 days of treatment initiation.~Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy, other prior system anticancer therapy, radiotherapy or surgery.~Women of childbearing potential must agree to use highly effective methods of birth control.~All participants must agree to use double barrier contraception during study participation and for at least 2 months after the last dose of study drug.~Additional criteria may apply.~Exclusion Criteria:~Use of an investigational agent or an investigational device within 28 days before administration of first dose of NKTR-214.~Females who are pregnant or breastfeeding.~Participants who have an active autoimmune disease requiring systemic treatment within the past 3 months or have a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents.~Active central nervous system (CNS) metastases.~Prior surgery or radiotherapy within 14 days of therapy.~Participants who have had < 28 days since the last chemotherapy, immunotherapy, biological therapy, or < 14 days from approved tyrosine kinase inhibitor (TKI) therapy (sunitinib, sorafenib, vemurafenib, dabrafenib, cobimetinib), or systemic or inhaled steroid therapy at doses greater than 10mg of prednisone or equivalent before administration of the first dose of study medication.~Participants' inability to adhere to or tolerate protocol or study procedures.~Additional criteria may apply.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of NKTR-214 as Evaluated by Incidence of Drug-related Adverse Events (AEs) | This outcome quantifies the number and types of adverse events associated with NKTR-214. | 30 days after last dose, approximately 533 days |
| Tolerability of NKTR-214 as Evaluated by Incidence of Dose Limiting Toxicities (DLTs) | The data below reflects the incidence of Dose Limiting Toxicity Events observed in this trial. | 30 days after last dose, up to 533 days |
|
Metastatic Solid Tumors, Locally Advanced Solid Tumors
|
Neoplasms
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NKTR-214 Dose Escalation<br>This is a first in human, open-label, sequential dose escalation and expansion Phase 1 study of NKTR--214 in adult patients with locally advanced and metastatic solid tumors. The Phase 1 stage of the study is designed as an open-label dose escalation trial of NKTR--214 in participants with locally advanced or metastatic solid tumors. The goal of the dose escalation stage of the study is to find the recommended phase 2 dose, to evaluate the efficacy of NKTR--214 by assessing the objective response rate and to evaluate the safety of NKTR-214. Immunological biomarkers in plasma and tumor samples will also be measured. | Drug: NKTR-214<br>* Participants in the dose escalation cohorts will be treated every 21 days (q21d) or every 14 days (q14d) until tumor progression.<br>|
|
A Phase 1/2 Multicenter Dose Escalation and Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumors
Study Overview
=================
Brief Summary
-----------------
This is a first in human, open-label, sequential dose escalation and expansion Phase 1 study of NKTR-214 in adult patients with locally advanced or metastatic solid tumors.
Official Title
-----------------
An Open-Label, Multicenter, Dose Escalation And Expansion Study Of NKTR-214 In Subjects With Locally Advanced Or Metastatic Solid Tumor Malignancies
Conditions
-----------------
Unspecified Adult Solid Tumor, Protocol Specific
Intervention / Treatment
-----------------
* Drug: NKTR-214
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor. Received 1 or 2 prior lines of therapy. Life expectancy >12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. Measurable disease per RECIST v1.1. Demonstrated adequate organ function within 14 days of treatment initiation. Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy, other prior system anticancer therapy, radiotherapy or surgery. Women of childbearing potential must agree to use highly effective methods of birth control. All participants must agree to use double barrier contraception during study participation and for at least 2 months after the last dose of study drug. Additional criteria may apply. Exclusion Criteria: Use of an investigational agent or an investigational device within 28 days before administration of first dose of NKTR-214. Females who are pregnant or breastfeeding. Participants who have an active autoimmune disease requiring systemic treatment within the past 3 months or have a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents. Active central nervous system (CNS) metastases. Prior surgery or radiotherapy within 14 days of therapy. Participants who have had < 28 days since the last chemotherapy, immunotherapy, biological therapy, or < 14 days from approved tyrosine kinase inhibitor (TKI) therapy (sunitinib, sorafenib, vemurafenib, dabrafenib, cobimetinib), or systemic or inhaled steroid therapy at doses greater than 10mg of prednisone or equivalent before administration of the first dose of study medication. Participants' inability to adhere to or tolerate protocol or study procedures. Additional criteria may apply.
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: Sequential Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NKTR-214 Dose Escalation<br>This is a first in human, open-label, sequential dose escalation and expansion Phase 1 study of NKTR--214 in adult patients with locally advanced and metastatic solid tumors. The Phase 1 stage of the study is designed as an open-label dose escalation trial of NKTR--214 in participants with locally advanced or metastatic solid tumors. The goal of the dose escalation stage of the study is to find the recommended phase 2 dose, to evaluate the efficacy of NKTR--214 by assessing the objective response rate and to evaluate the safety of NKTR-214. Immunological biomarkers in plasma and tumor samples will also be measured. | Drug: NKTR-214<br>* Participants in the dose escalation cohorts will be treated every 21 days (q21d) or every 14 days (q14d) until tumor progression.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of NKTR-214 as Evaluated by Incidence of Drug-related Adverse Events (AEs) | This outcome quantifies the number and types of adverse events associated with NKTR-214. | 30 days after last dose, approximately 533 days |
| Tolerability of NKTR-214 as Evaluated by Incidence of Dose Limiting Toxicities (DLTs) | The data below reflects the incidence of Dose Limiting Toxicity Events observed in this trial. | 30 days after last dose, up to 533 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metastatic Solid Tumors, Locally Advanced Solid Tumors
|
||
NCT04911023
|
Comparison of Fissurectomy to Fissurectomy With Anoplasty
|
Surgery is sometimes necessary to relieve patients with chronic anal fissure. It consists of resecting the edges of the fissure to make a wound larger than the initial fissure, in order to obtain healing. Thus, the edges of the wound do not stick together and the healing is done from the bottom of the wound. This procedure is widely performed in France with results that seem satisfactory. In addition to resection of the fissure, a partial closure of the wound can be associated with a small flap of rectal mucosa which is sutured with a few absorbable stitches: this is anoplasty.
|
There is some debate as to whether to perform a fissurectomy alone or to complement it with an anoplasty to accelerate healing. The choice of technique performed depends on the training and habits of the operators but the results of fissurectomy alone and fissurectomy with anoplasty have never been compared. In the medical-surgical proctology department of the Groupe Hospitalier Paris Saint-Joseph (GHPSJ), both procedures are performed. The investigators therefore decided to compare the after-effects of fissurectomies alone with those of fissurectomies with anoplasty that were performed in the department in 2019. The choice between the 2 procedures is left exclusively to the discretion of the operator. The criteria for choice between the two patient populations are not different.
|
Comparison of Fissurectomy to Fissurectomy With Anoplasty
|
Fissure Rectal
|
Inclusion Criteria:~Major patient~Patient managed in the proctology department of Groupe hospitalier Paris Saint-Joseph for single posterior idiopathic fissures (anoplasty possible only in the context of non-infected posterior fissure) between January 1 and December 31, 2019 by fissurectomy alone or fissurectomy with anoplasty~Exclusion Criteria:~anterior or bipolar fissure~infected fissure~history of proctological surgery~Crohn's disease~HIV infection~tubercular lesion validated by anatomopathology~history of pelvic-perineal radiotherapy~Tumor cells on histology~fissurectomy +/- anoplasty associated with another proctological surgical procedure~patient under guardianship or curatorship~patient deprived of liberty~patient under court protection~Patient opposing the use of his data for this research
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the effectiveness of the two techniques on the disappearance of pain related to anal fissure | Difference between the 2 groups in terms of percent of patients free of pain at Day 15 postoperatively | Day 15 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the two techniques for the rate of complications | Difference between the 2 groups of patients at Day 15 post-operative in terms of complication rate | Day 15 |
| Compare the two techniques for the healing rate | Difference between the 2 groups of patients at Day 15 post-operative in terms of healing rate | Day 15 |
| Compare the two techniques for the rate of non-healing | Difference between the 2 groups of patients at Day 15 post-operative in terms of non-healing rate | Day 15 |
| Compare the two techniques for the recurrence rate | Difference between the 2 groups of patients at Day 15 post-operative in terms of revision rate | Day 15 |
| Compare the two techniques for the rate of revision surgery | Difference between the 2 groups of patients at D15 postoperatively in terms of revision rate | Day 15 |
| Search for predictive factors of failure of each technique | Uni- and multivariate analyses to identify risk factors for failure for each technique | Day 15 |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients operated by fissurectomy<br> | |
| Patients operated by fissurectomy with anoplasty<br> | |
|
Comparison of Fissurectomy to Fissurectomy With Anoplasty
Study Overview
=================
Brief Summary
-----------------
Surgery is sometimes necessary to relieve patients with chronic anal fissure. It consists of resecting the edges of the fissure to make a wound larger than the initial fissure, in order to obtain healing. Thus, the edges of the wound do not stick together and the healing is done from the bottom of the wound. This procedure is widely performed in France with results that seem satisfactory. In addition to resection of the fissure, a partial closure of the wound can be associated with a small flap of rectal mucosa which is sutured with a few absorbable stitches: this is anoplasty.
Detailed Description
-----------------
There is some debate as to whether to perform a fissurectomy alone or to complement it with an anoplasty to accelerate healing. The choice of technique performed depends on the training and habits of the operators but the results of fissurectomy alone and fissurectomy with anoplasty have never been compared. In the medical-surgical proctology department of the Groupe Hospitalier Paris Saint-Joseph (GHPSJ), both procedures are performed. The investigators therefore decided to compare the after-effects of fissurectomies alone with those of fissurectomies with anoplasty that were performed in the department in 2019. The choice between the 2 procedures is left exclusively to the discretion of the operator. The criteria for choice between the two patient populations are not different.
Official Title
-----------------
Comparison of Fissurectomy to Fissurectomy With Anoplasty
Conditions
-----------------
Fissure Rectal
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Major patient Patient managed in the proctology department of Groupe hospitalier Paris Saint-Joseph for single posterior idiopathic fissures (anoplasty possible only in the context of non-infected posterior fissure) between January 1 and December 31, 2019 by fissurectomy alone or fissurectomy with anoplasty Exclusion Criteria: anterior or bipolar fissure infected fissure history of proctological surgery Crohn's disease HIV infection tubercular lesion validated by anatomopathology history of pelvic-perineal radiotherapy Tumor cells on histology fissurectomy +/- anoplasty associated with another proctological surgical procedure patient under guardianship or curatorship patient deprived of liberty patient under court protection Patient opposing the use of his data for this research
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 |
| --- | --- |
| Patients operated by fissurectomy<br> | |
| Patients operated by fissurectomy with anoplasty<br> | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the effectiveness of the two techniques on the disappearance of pain related to anal fissure | Difference between the 2 groups in terms of percent of patients free of pain at Day 15 postoperatively | Day 15 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the two techniques for the rate of complications | Difference between the 2 groups of patients at Day 15 post-operative in terms of complication rate | Day 15 |
| Compare the two techniques for the healing rate | Difference between the 2 groups of patients at Day 15 post-operative in terms of healing rate | Day 15 |
| Compare the two techniques for the rate of non-healing | Difference between the 2 groups of patients at Day 15 post-operative in terms of non-healing rate | Day 15 |
| Compare the two techniques for the recurrence rate | Difference between the 2 groups of patients at Day 15 post-operative in terms of revision rate | Day 15 |
| Compare the two techniques for the rate of revision surgery | Difference between the 2 groups of patients at D15 postoperatively in terms of revision rate | Day 15 |
| Search for predictive factors of failure of each technique | Uni- and multivariate analyses to identify risk factors for failure for each technique | Day 15 |
|
||||
NCT04355962
|
Sevoflurane in COVID-19 ARDS (SevCov)
|
The purpose of this trial is to study the effect of initial temporary sevoflurane sedation on mortality and persistent organ dysfunction (POD) in survivors at day 28 after ICU admission in the population of patients suffering from COVID-19 ARDS.
|
The corona virus disease 19 (COVID-19) pandemic, caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), is spreading rapidly across Europe. While data from European centers are still missing, several publications from Chinese centers are available. Respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality, and may be caused or exacerbated by a 'cytokine storm syndrome'.~Recent trials from our group demonstrated that the volatile anesthetic sevoflurane administered during ventilation of patients has anti-inflammatory properties. Moreover, in in vivo studies volatile anesthetics reduce the severity of ARDS compared to intravenous sedation, which has been confirmed in a clinical pilot trial. Attenuating ARDS and thereby improving oxygenation strongly decreases morbidity and mortality of patients.
|
Sevoflurane Sedation in COVID-19 ARDS Patients to Reduce Lung Injury: a Randomized Controlled Trial
|
ARDS, Human, Coronavirus
|
* Drug: Sevoflurane
* Drug: Intravenous drug
|
Inclusion Criteria:~SARS-CoV-2 infection (positive testing) or computed tomography (CT) scan-suspected COVID-19 ARDS~Male and female patients, age 18 to 85 years~ICU patients with ARDS defined as PaO2/FiO2 < 200mmHg (=26.6kPa)~Time of intubation not longer than 24 hours~QTc Time (ECG) not longer than 470 ms ♂ (male)/ 480 ms ♀ (female)~Sedation and mechanical ventilation in ICU~Informed consent, signed by a representative or by an independent physician~Exclusion Criteria:~High dose systemic corticosteroids in the phase before hospitalization (> 10mg/d prednisone or equivalent dose)~Significant concomitant disease (acute cerebral vascular event, acute coronary syndrome, seizure, burn, neuromuscular disease)~Organ transplant~AIDS~Pregnancy and/or breastfeeding~Use of cytokine absorber
|
18 Years
|
85 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a randomized, controlled multi-center trial
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome of death rate (rate of patients that did not survive) and organ failure rate (rate of patients surviving with persistent organ dysfunction) at day 28 | The effect of sevoflurane application on mortality (rate of patients that does not survive 28 days) and persistent organ dysfunction (rate of patients surviving with a persistent organ failure at day 28) will be assessed. Organ failures are defined as pulmonary failure (necessity of ventilation); cardiovascular failure (need of vasopressors), retail failure (need of renal replacement therapy) | 28 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay ICU | The effect of sevoflurane application on the length of stay at ICU will be determined. | 28 days |
| Plasma Inflammatory markers | The impact of sevoflurane on the course of inflammatory markers will be evaluated (pro-calcitonin, PCT; c-reactive protein, CRP; interleukin 6, IL-6; monocyte chemoattractant protein 1, MCP-1) | 8 days |
| Length of stay at hospital | The effect of sevoflurane application on the length of stay at hospital will be determined. | 28 days |
| Sex-related differences in complications | Sex-related differences in complications will be assessed | 28 days |
|
COVID-19, ARDS
|
Sevoflurane, Platelet Aggregation Inhibitors, Anesthetics, Inhalation, Anesthetics, General, Anesthetics, Central Nervous System Depressants, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sevoflurane Sedation<br>Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS | Drug: Sevoflurane<br>* Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS<br>|
| Active Comparator: Intravenous<br>No use of sevoflurane, but current intravenous sedation at discretion of the ICU physician in charge, e.g. with propofol, fentanyl, midazolam and dexmedetomidine | Drug: Intravenous drug<br>* Intravenous sedation in control group will be continued as initiated at the ICU e.g. propofol, fentanyl, midazolam, dexmedetomidine<br>|
|
Sevoflurane in COVID-19 ARDS (SevCov)
Study Overview
=================
Brief Summary
-----------------
The purpose of this trial is to study the effect of initial temporary sevoflurane sedation on mortality and persistent organ dysfunction (POD) in survivors at day 28 after ICU admission in the population of patients suffering from COVID-19 ARDS.
Detailed Description
-----------------
The corona virus disease 19 (COVID-19) pandemic, caused by the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), is spreading rapidly across Europe. While data from European centers are still missing, several publications from Chinese centers are available. Respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality, and may be caused or exacerbated by a 'cytokine storm syndrome'. Recent trials from our group demonstrated that the volatile anesthetic sevoflurane administered during ventilation of patients has anti-inflammatory properties. Moreover, in in vivo studies volatile anesthetics reduce the severity of ARDS compared to intravenous sedation, which has been confirmed in a clinical pilot trial. Attenuating ARDS and thereby improving oxygenation strongly decreases morbidity and mortality of patients.
Official Title
-----------------
Sevoflurane Sedation in COVID-19 ARDS Patients to Reduce Lung Injury: a Randomized Controlled Trial
Conditions
-----------------
ARDS, Human, Coronavirus
Intervention / Treatment
-----------------
* Drug: Sevoflurane
* Drug: Intravenous drug
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: SARS-CoV-2 infection (positive testing) or computed tomography (CT) scan-suspected COVID-19 ARDS Male and female patients, age 18 to 85 years ICU patients with ARDS defined as PaO2/FiO2 < 200mmHg (=26.6kPa) Time of intubation not longer than 24 hours QTc Time (ECG) not longer than 470 ms ♂ (male)/ 480 ms ♀ (female) Sedation and mechanical ventilation in ICU Informed consent, signed by a representative or by an independent physician Exclusion Criteria: High dose systemic corticosteroids in the phase before hospitalization (> 10mg/d prednisone or equivalent dose) Significant concomitant disease (acute cerebral vascular event, acute coronary syndrome, seizure, burn, neuromuscular disease) Organ transplant AIDS Pregnancy and/or breastfeeding Use of cytokine absorber
Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
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No
Study Plan
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How is the study designed?
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Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a randomized, controlled multi-center trial
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sevoflurane Sedation<br>Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS | Drug: Sevoflurane<br>* Sedation with sevoflurane (etSevo 0.5-1.5 Vol %) for 48 hours in patients with COVID-19 ARDS<br>|
| Active Comparator: Intravenous<br>No use of sevoflurane, but current intravenous sedation at discretion of the ICU physician in charge, e.g. with propofol, fentanyl, midazolam and dexmedetomidine | Drug: Intravenous drug<br>* Intravenous sedation in control group will be continued as initiated at the ICU e.g. propofol, fentanyl, midazolam, dexmedetomidine<br>|
What is the study measuring?
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Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome of death rate (rate of patients that did not survive) and organ failure rate (rate of patients surviving with persistent organ dysfunction) at day 28 | The effect of sevoflurane application on mortality (rate of patients that does not survive 28 days) and persistent organ dysfunction (rate of patients surviving with a persistent organ failure at day 28) will be assessed. Organ failures are defined as pulmonary failure (necessity of ventilation); cardiovascular failure (need of vasopressors), retail failure (need of renal replacement therapy) | 28 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay ICU | The effect of sevoflurane application on the length of stay at ICU will be determined. | 28 days |
| Plasma Inflammatory markers | The impact of sevoflurane on the course of inflammatory markers will be evaluated (pro-calcitonin, PCT; c-reactive protein, CRP; interleukin 6, IL-6; monocyte chemoattractant protein 1, MCP-1) | 8 days |
| Length of stay at hospital | The effect of sevoflurane application on the length of stay at hospital will be determined. | 28 days |
| Sex-related differences in complications | Sex-related differences in complications will be assessed | 28 days |
Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, ARDS
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NCT02736409
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An Extension Study to Evaluate Maintenance of Efficacy and Long-term Treatment Effect of Oral Budesonide Suspension (OBS) in Adults and Adolescents With Eosinophilic Esophagitis (EoE)
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This is a multicenter, double- blind extension study of Oral Budesonide Suspension (OBS) in adults and adolescents (11 to 55 years of age, inclusive) with Eosinophilic Esophagitis (EoE) who have completed participation in the SHP621-301 induction study (NCT02605837). The primary objective is to evaluate the maintenance of efficacy of OBS over 36 weeks. Maintenance of efficacy will be measured by the peak eosinophilic count and Dysphagia Symptom Questionnaire (DSQ) score.
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A Phase 3, Multicenter, Double-blind Extension Study to Evaluate Maintenance of Efficacy of Oral Budesonide Suspension (OBS) and Long-term Treatment Effect of OBS in Adolescent and Adult Subjects (11 to 55 Years of Age, Inclusive) With Eosinophilic Esophagitis (EoE)
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Eosinophilic Esophagitis (EoE)
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* Drug: Oral Budesonide Suspension (OBS)
* Drug: Placebo
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Inclusion Criteria:~Subject completed SHP621-301 induction study.~Subject is able to provide written informed consent (subject, parent or legal guardian and, as appropriate, subject assent) to participate in the study before completing any study-related procedures.~Subject is male or female aged 11-55 years, inclusive, at time of consent for SHP621-301 study.~Subject is willing and able to continue any dietary therapy, environmental therapy, and/or medical regimens (including gastric acid suppression; see exclusions below) in effect at the screening visit (Visit 0). There should be no changes to these regimens during study participation.~All female subjects must have a negative serum pregnancy test (beta-human chorionic gonadotropin [β-hCG]) prior to enrollment into the study. Females of childbearing potential must agree to continue acceptable birth control measures (eg, abstinence, stable oral contraceptives, or double-barrier methods) throughout study participation and for 30 days following the last dose of investigational product.~Subject is willing and has an understanding and ability to fully comply with study procedures including DSQ compliance (completed the DSQ on ≥70% of days in any 2 consecutive weeks of the screening period)and restrictions defined in this protocol~Exclusion Criteria:~Subject has changes in medications that could affect the study or diet in the weeks since the final treatment evaluation visit (Visit 4) of the SHP621-301 study.~Subject using immunomodulatory therapy since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated use of immunomodulatory therapy during the treatment period (except for any ongoing regimen of allergy shots); any temporary use (≤7 days) or initiation of new steroid treatment during the study should be documented and discussed with the medical monitor prospectively but cannot occur within 4 weeks of scheduled EGDs.~Subject using swallowed topical corticosteroid for EoE or systemic corticosteroid for any condition since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated use during the treatment period; any temporary use (≤7 days) or initiation of new steroid treatment during the study should be documented and discussed with medical monitor prospectively but cannot occur within the 4 weeks of the scheduled EGDs.~Subject on inhaled or intranasal steroids and not on a stable dose between the baseline visit (Visit 1) of the SHP621-301 study and the screening EGD of this study.~Subject has initiated, discontinued, or changed dosage regimen of proton pump inhibitors (PPIs), H2 antagonists, antacids, antihistamines, or leukotriene inhibitors for any condition (such as gastroesophageal reflux disease, asthma or allergic rhinitis) since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated changes in the use of such medications during the treatment period.~Subject using Cytochrome P450 3A4 inhibitors (eg, ketoconazole, grapefruit juice) since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated use of such medications during the treatment period.~Subject has an appearance on screening EGD of an esophageal stricture (high grade), as defined by the presence of a lesion that does not allow passage of a diagnostic adult upper endoscope (eg, with an insertion tube diameter of >9mm).~Subject is on a pure liquid diet or the six-food elimination diet.~Subject has presence of esophageal varices at the EGD at the final treatment evaluation visit (Visit 4) of the SHP621-301 study.~Subject has any current disease of the gastrointestinal tract, aside from EoE, including eosinophilic gastritis, enteritis, colitis, or proctitis, inflammatory bowel disease, or celiac disease.~Subject has other diseases causing or associated with esophageal eosinophilia, including hypereosinophilic syndrome, collagen vascular disease, vasculitis, achalasia, or parasitic infection.~Subject has oropharyngeal or esophageal candidiasis that failed to respond to previous treatment.~Diagnosis with oropharyngeal or esophageal candidiasis at or since the final treatment evaluation visit (Visit 4) of the SHP621-301 study is not an exclusion as long as the subject received treatment for candidiasis and is expected to respond to treatment.~Subject has acute or chronic infection or immunodeficiency condition, including tuberculosis, fungal, bacterial, viral/parasite infection, ocular herpes simplex, or chicken pox/measles.~Subject has upper gastrointestinal bleeding identified in the EGD at the final treatment evaluation visit (Visit 4) of the SHP621-301 study or since the final treatment evaluation visit (Visit 4) of the SHP621-301 study.~Subject has evidence of active infection with Helicobacter pylori.~Subject has evidence of unstable asthma since the final treatment evaluation visit (Visit 4) of the SHP621-301 study.~Subject is female and pregnant or nursing.~Subject has a history of intolerance, hypersensitivity, or idiosyncratic reaction to budesonide (or any other corticosteroids), or to any other ingredients of the study medication.~Subject has a history or high risk of noncompliance with treatment or regular clinic visits.~Subject is on sucralfate or anticipates using sucralfate during the treatment period.
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11 Years
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55 Years
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All
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No
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Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
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| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Who Had Relapse During the Entire Week 36 Period | Relapse (Yes/No) was defined as meeting both the eosinophil histology relapse criterion and the dysphagia symptom relapse criterion. Eosinophil histology relapse was defined as an eosinophil count of greater than or equal to(> or =) 15 per high-power field (eos/hpf) from at least 2 of 3 levels of the esophagus. Dysphagia symptom relapse was defined as having at least 4 days of dysphagia (with answer 'Yes' for question 2 in DSQ [Dysphagia Symptom Questionnaire]) in the 2-week period prior to the scheduled visit, as determined by the DSQ. | Week 36 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Long-term Treatment Response From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | Long-term response from SHP621-301 baseline defined: histologic response,defined as peak eosinophil count of less than or equal to(< or =)6/HPF across all available esophageal levels at Week 36 and Dysphagia symptom response 1,defined as >or= 30 percent(%) reduction in DSQ combined score(Questions [Q] 2+3) from baseline of SHP621-301 to Week 36.DSQcontain 4 questions,all participants used diary,responded to Q1(didyoueatsolid food),Q2(did food pass slowly or get stuck). If participant's answer to Q2 was No,diary ended for day. If participant answered Yes,he/she advanced to Q3(didyouhavetodoanything to make food go downorget relief), Q4(extent to which participant experienced pain while swallowing).DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/Number of diaries reported with non-missing data.Scale range was0-2 forQ2 and 0-4 forQ 3.Scale range for DSQ combined score was 0-84.Highervaluesrepresentingworseoutcome.Negative change from baseline indicates symptoms decreased. | Week 36 |
| Proportion of Participants With Long-term Treatment Response From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | Long-term response from baseline defined: histologic response, defined as peak eosinophil count of less than or equal to(< or =) 6/HPF across all available esophageal levels at Week 36 and Dysphagia symptom response 1,defined as >or= 30 percent(%) reduction in DSQ combined score (Questions [Q] 2+3) from baseline of SHP621-301 to Week 36.DSQcontain 4 questions,all participants used diary,responded to Q1(did you eat solid food),Q2(did food pass slowly or get stuck). If participant's answer to Q2 was No,diary ended for day. If participant answered Yes,he/she advanced to Q3(didyouhavetodoanything to make food go downorget relief), Q4(extent to which participant experienced pain while swallowing).DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/Number of diaries reported with non-missing data.Scale range was0-2 forQ2 and 0-4 forQ 3.Scale range for DSQ combined score was 0-84. Higher values representing worse outcome.Negative change from baseline indicates symptoms decreased. | Week 36 |
| Proportion of Participants Who Had a Histologic Response (Eosinophil Count of Less Than or Equal to (<or=6)/High-Powered Field [HPF]) at Week 12 and Week 36 | Histology response was defined as a peak eosinophil count of <or=6/HPF across all available levels at Week 12 and Week 36. | Week 12 and Week 36 |
| Proportion of Participants Who Had at Least a 30 Percent (%) Change in DSQ Combined Score From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 12 and Week 36 | Dysphagia symptom response with respect to the baseline of induction study (SHP621-301 [NCT02605837]) was defined as 30% reduction in DSQ combined score (questions 2+3) at Week 12 and Week 36 of current study from baseline of the induction study. DSQ contain 4 questions, all participants used a diary and responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was No, then diary ended for that day. If participant answered Yes,he/she advanced to Q3 (did you have to do anything to make food go down or get relief) and Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3. Scale range for DSQ combined score was 0-84. Higher values representing worse outcome. Negative change from baseline indicates symptoms decreased. | Baseline of SHP621-301 (NCT02605837), Week 12 and Week 36 |
| Proportion of Participants Who Had at Least a 30 Percent (%) Change in DSQ Combined Score From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36 | Dysphagia symptom response with respect to the baseline of current study (SHP621-302 [NCT02736409]) was defined as 30% reduction in DSQ combined score (questions 2+3) at Week 12 and Week 36 from baseline of the current study. DSQ contain 4 questions, all participants used diary and responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was No, then diary ended for that day. If participant answered Yes,he/she advanced to Q3 (did you have to do anything to make food go down or get relief) and Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q 3. Scale range for DSQ combined score was 0-84. Higher values representing a worse outcome. A Negative change from baseline indicates symptoms decreased. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36 |
| Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Total Endoscopy Score at Week 12 and Week 36 of Current Study | Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 categories: 1) exudates or plaques (grade 0-2); 2) fixed esophageal rings (grade 0-3); 3) edema (grade 0-2); 4) furrows (grade 0-2); and 5) strictures (grade 0-1). An endoscopy score for each category was calculated and summed for each anatomic location (proximal and distal). The minimum and maximum endoscopy score was 0 and 10 points respectively for each location (proximal and distal) and the total endoscopy score was the sum of the scores for the proximal and distal locations (maximum total score of 20 points respectively). The higher score indicated worse appearance. A negative change from baseline indicates that appearance improved. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36 |
| Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Total Endoscopy Score at Week 12 and Week 36 | Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 categories: 1) exudates or plaques (grade 0-2); 2) fixed esophageal rings (grade 0-3); 3) edema (grade 0-2); 4) furrows (grade 0-2); and 5) strictures (grade 0-1). An endoscopy score for each category was calculated and summed for each anatomic location (proximal and distal). The minimum and maximum endoscopy score was 0 and 10 points respectively for each location (proximal and distal) and the total endoscopy score was the sum of the scores for the proximal and distal locations (maximum total score of 20 points respectively). The higher score indicated worse appearance. A negative change from baseline indicates that appearance improved. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36 |
| Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Peak Eosinophil Count at Week 12 and Week 36 of Current Study | Change from induction study (SHP621-301 [NCT02605837]) baseline in peak eosinophil count at Week 12 and Week 36 of current study was reported. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36 |
| Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Peak Eosinophil Count at Week 12 and Week 36 | Change from current study (SHP621-302 [NCT02736409]) baseline in peak eosinophil count at Week 12 and Week 36 was reported. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36 |
| Proportion of Participants Who Had Peak Eosinophil Count Less Than (<) 15/High-Powered Field (HPF) at Week 12 and Week 36 | Proportion of participants who had Peak Eosinophil Count less than (<) 15/HPF at Week 12 and Week 36 were reported. | Week 12 and Week 36 |
| Proportion of Participants Who Had Peak Eosinophil Count Less Than or Equal to (< or =) 1/High-Powered Field (HPF) at Week 12 and Week 36 | Proportion of participants who had Peak Eosinophil Count less than or equal to (< or =) 1/High-Powered Field (HPF) at Week 12 and Week 36 were reported. | Week 12 and Week 36 |
| Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Peak Eosinophil Count for Each Available Esophageal Level (Proximal, Mid, and Distal) at Week 12 and Week 36 of Current Study | Change from induction study (SHP621-301 [NCT02605837]) baseline in peak eosinophil count for each available esophageal level (proximal, mid, distal) at Week 12 and Week 36 of current study were reported. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36 |
| Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Peak Eosinophil Count for Each Available Esophageal Level (Proximal, Mid, and Distal) at Week 12 and Week 36 | Change from current study (SHP621-302 [NCT02736409]) baseline in peak eosinophil count for each available esophageal level (proximal, mid, distal) at Week 12 and Week 36 were reported. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36 |
| Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in the Histopathologic Epithelial Features Combined Total Score (Grade and Stage) at Week 12 an Week 36 of Current Study | Eight histopathologic epithelial features (basal layer hyperplasia, eosinophil peak, abscesses, surface layering, dilated intercellular spaces, surface alteration, dyskeratotic epithelial cells, lamina propria fibrosis) are scored on a 4-point scale (0=normal, 3=worst) for both the severity of the abnormality (i.e., grade) and the amount of tissue affected by the abnormality (i.e. stage). Thus each of the 3 levels had a minimum score of 0 and maximum possible score of 24, and a possible total grade or stage score of 72 for a maximum combined score of 144. Combined total score ratio (TSR) =(proximal TSR + mid TSR + distal TSR)/N, where N is the number of non missing sections for TSR. A negative change from baseline indicates that epithelial inflammation decreased. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36 |
| Change From Current Study (SHP621-302 [NCT02736409]) Baseline in the Histopathologic Epithelial Features Combined Total Score (Grade and Stage) at Week 12 and Week 36 | Eight histopathologic epithelial features (basal layer hyperplasia, eosinophil peak, abscesses, surface layering, dilated intercellular spaces, surface alteration, dyskeratotic epithelial cells, lamina propria fibrosis) are scored on a 4-point scale (0=normal, 3=worst) for both the severity of the abnormality (i.e., grade) and the amount of tissue affected by the abnormality (i.e. stage). Thus each of the 3 levels had a minimum score of 0 and maximum possible score of 24, and a possible total grade or stage score of 72 for a maximum combined score of 144. Combined total score ratio (TSR) =(proximal TSR + mid TSR + distal TSR)/N, where N is the number of non missing sections for TSR. A negative change from baseline indicates that epithelial inflammation decreased. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36 |
| Proportion of Participants Who Had Greater Than or Equal to (>or=) 50 Percent (%) Reduction in DSQ Combined Score From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 12 and Week 36 | Dysphagia symptom response from the baseline of SHP621-301, was defined as >or=50% reduction in DSQ combined score (questions [Q] 2+3) from baseline of the induction study at Week 12 and 36 of current study. DSQ contained 4Q, all participants used diary, and responded to Q1(did you eat solid food) and Q2(didfood passslowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If a participant answered 'Yes', he/she advanced to Q3(did you have to do anything to make food go down or get relief) and 4(extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0-84, with higher values representing a worse outcome. Anegative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Proportion of Participants Who Had Greater Than or Equal to (>or=) 50 Percent (%) Reduction in DSQ Combined Score From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36 | Dysphagia symptom response from the baseline of SHP621-302, was defined as >or=50% reduction in DSQ combined score (questions 2+3) from baseline of the induction study at Week 36 of current study. DSQ contained 4Q, all participants used diary, and responded to Q1 (did you eat solid food) and Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If a participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make food go down or get relief) and 4(extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0-84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Change in the DSQ Combined Score (Questions 2+3) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | DSQ contain 4 questions (Q), all participants used a diary, responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make food go down or get relief), Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3. Scale range for DSQ combined score was 0-84. Higher values representing a worse outcome. A Negative change from baseline indicates symptoms decreased. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Change in the DSQ Combined Score (Questions 2+3) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | DSQ contain 4 questions, all participants used a diary, responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make food go down or get relief), Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3. Scale range for DSQ combined score was 0-84. Higher values representing a worse outcome. A Negative change from baseline indicates symptoms decreased. Change in DSQ combined score (Questions 2+3) from baseline of current study at Week 36 was reported. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
| Percent Change in the DSQ Combined Score (Questions 2+3) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | Percent change in DSQ combined score from Induction Study (SHP621-301 [NCT02605837]) baseline to current study (SHP621-302 [NCT02736409]) final treatment period (Week 36) was reported. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Percent Change in the DSQ Combined Score (Questions 2+3) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | Percent change in DSQ combined score from baseline to final treatment period (Week 36) of current study was reported. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
| Proportion of Participants Who Had Overall Binary Response I From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 12 and Week 36 of Current Study | Overall binary response I was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 30% reduction in DSQ combined score from baseline of the induction study (SHP621-301 [NCT02605837]) at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Proportion of Participants Who Had Overall Binary Response I From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36 | Overall binary response I was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 30% reduction in DSQ combined score from baseline at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Proportion of Participants Who Had Overall Binary Response II From Induction Study SHP621-301 (NCT02605837) Baseline at Week 12 and Week 36 of Current Study | Overall binary response II was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 50% reduction in DSQ combined score from baseline of the SHP621-301 study at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Proportion of Participants Who Had Overall Binary Response II From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36 | Overall binary response II was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 30% reduction in DSQ combined score from baseline at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Change in the DSQ + Pain Score (Questions 2+3+4) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ + pain score was calculated by summing the scores of responses to questions 2, 3, and 4 by using following formula: DSQ + pain score= ([sum of points from questions 2+3+4 in the daily DSQ] ×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2, 0 - 4 for question 3 and 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ + pain score was 0 - 140, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Change in the DSQ+ Pain Score (Questions 2+3+4) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | DSQ contained 4 questions, all participants used a diary, and responded to Questions (Q) 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Q2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ + pain score was calculated by summing the scores of responses to Questions 2, 3, and 4. Question 1 was excluded from the DSQ + pain score. DSQ + pain score=(Sum of points from questions 2+3+4 in the daily DSQ)*14 Days/Number of dairies reported with non-missing data. Scale range was 0 - 2 for Q2, 0 - 4 for Q3 and 0 - 4 for Q4, with higher values representing a worse outcome. Scale range for DSQ + pain score was 0 - 140, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
| Change in the DSQ Pain Score (Question 4) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ pain score was calculated by summing the scores of responses to Question 4 only. DSQ pain score=(sum of points from questions 4 in the daily DSQ)*14 days/Number of diaries reported with non-missing data. Scale range was 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ pain score was 0 - 56, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Change in the DSQ Pain Score (Question 4) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ pain score was calculated by summing the scores of responses to Question 4 only. DSQ pain score=(sum of points from questions 4 in the daily DSQ)*14 days/Number of diaries reported with non-missing data. Scale range was 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ pain score was 0 - 56, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
| Number of Participants With Treatment Emergent Adverse Events (TEAE's) | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started or deteriorated on or after the date of the first dose of double-blind IP in SHP621-302 and through the safety follow-up contact, or 31 days after the last dose of IP for participants who did not have a safety follow-up contact. | From start of the study drug administration up to follow up (Week 40) |
| Change in DXA (Dual-Energy X-ray Absorptiometry) Imaging Results (Location: Lumbar Spine [L1-L4]) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Baseline of SHP621-301 is determined at Week 0 in the SHP621-301 study. Here in this outcome measure DXA measurement of L1-L4 were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Change in DXA Imaging Results (Location: Lumbar Spine [L1-L4]) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Here in this outcome measure DXA measurement of L1-L4 were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
| Change in DXA Imaging Results (Location: Whole Body) From Baseline of Induction Study (SHP621-301 [NCT02605837]) at Week 36 of Current Study | The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Baseline of SHP621-301 is determined at Week 0 in the SHP621-301 study. Here in this outcome measure DXA measurement of whole body (except head) were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Change in DXA Imaging Results (Location: Whole Body) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Here in this outcome measure DXA measurement of whole body (except head) were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
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Budesonide, Anti-Inflammatory Agents, Bronchodilator Agents, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Asthmatic Agents, Respiratory System Agents, Glucocorticoids, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arms A OBS Completers/ Responders<br>Arm A Oral Budesonide Suspension Completers/ Responders | Drug: Oral Budesonide Suspension (OBS)<br>* OBS 2mg twice daily<br>|
| Placebo Comparator: Arm B OBS Completers/ Responders<br>Arm B Oral Budesonide Suspension Completers/ Responders. 1:1 randomization for Arms A and B | Drug: Placebo<br>* Matching Placebo dose<br>|
| Experimental: Arm C OBS Completers/ Non-Responders<br>Arm C Oral Budesonide Suspension Completers/ Non-Responders | Drug: Oral Budesonide Suspension (OBS)<br>* OBS 2mg twice daily<br>|
| Experimental: Arm D Placebo Completers<br>Arm D Placebo Completers | Drug: Oral Budesonide Suspension (OBS)<br>* OBS 2mg twice daily<br>|
|
An Extension Study to Evaluate Maintenance of Efficacy and Long-term Treatment Effect of Oral Budesonide Suspension (OBS) in Adults and Adolescents With Eosinophilic Esophagitis (EoE)
Study Overview
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Brief Summary
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This is a multicenter, double- blind extension study of Oral Budesonide Suspension (OBS) in adults and adolescents (11 to 55 years of age, inclusive) with Eosinophilic Esophagitis (EoE) who have completed participation in the SHP621-301 induction study (NCT02605837). The primary objective is to evaluate the maintenance of efficacy of OBS over 36 weeks. Maintenance of efficacy will be measured by the peak eosinophilic count and Dysphagia Symptom Questionnaire (DSQ) score.
Official Title
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A Phase 3, Multicenter, Double-blind Extension Study to Evaluate Maintenance of Efficacy of Oral Budesonide Suspension (OBS) and Long-term Treatment Effect of OBS in Adolescent and Adult Subjects (11 to 55 Years of Age, Inclusive) With Eosinophilic Esophagitis (EoE)
Conditions
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Eosinophilic Esophagitis (EoE)
Intervention / Treatment
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* Drug: Oral Budesonide Suspension (OBS)
* Drug: Placebo
Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject completed SHP621-301 induction study. Subject is able to provide written informed consent (subject, parent or legal guardian and, as appropriate, subject assent) to participate in the study before completing any study-related procedures. Subject is male or female aged 11-55 years, inclusive, at time of consent for SHP621-301 study. Subject is willing and able to continue any dietary therapy, environmental therapy, and/or medical regimens (including gastric acid suppression; see exclusions below) in effect at the screening visit (Visit 0). There should be no changes to these regimens during study participation. All female subjects must have a negative serum pregnancy test (beta-human chorionic gonadotropin [β-hCG]) prior to enrollment into the study. Females of childbearing potential must agree to continue acceptable birth control measures (eg, abstinence, stable oral contraceptives, or double-barrier methods) throughout study participation and for 30 days following the last dose of investigational product. Subject is willing and has an understanding and ability to fully comply with study procedures including DSQ compliance (completed the DSQ on ≥70% of days in any 2 consecutive weeks of the screening period)and restrictions defined in this protocol Exclusion Criteria: Subject has changes in medications that could affect the study or diet in the weeks since the final treatment evaluation visit (Visit 4) of the SHP621-301 study. Subject using immunomodulatory therapy since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated use of immunomodulatory therapy during the treatment period (except for any ongoing regimen of allergy shots); any temporary use (≤7 days) or initiation of new steroid treatment during the study should be documented and discussed with the medical monitor prospectively but cannot occur within 4 weeks of scheduled EGDs. Subject using swallowed topical corticosteroid for EoE or systemic corticosteroid for any condition since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated use during the treatment period; any temporary use (≤7 days) or initiation of new steroid treatment during the study should be documented and discussed with medical monitor prospectively but cannot occur within the 4 weeks of the scheduled EGDs. Subject on inhaled or intranasal steroids and not on a stable dose between the baseline visit (Visit 1) of the SHP621-301 study and the screening EGD of this study. Subject has initiated, discontinued, or changed dosage regimen of proton pump inhibitors (PPIs), H2 antagonists, antacids, antihistamines, or leukotriene inhibitors for any condition (such as gastroesophageal reflux disease, asthma or allergic rhinitis) since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated changes in the use of such medications during the treatment period. Subject using Cytochrome P450 3A4 inhibitors (eg, ketoconazole, grapefruit juice) since the final treatment evaluation visit (Visit 4) of the SHP621-301 study or anticipated use of such medications during the treatment period. Subject has an appearance on screening EGD of an esophageal stricture (high grade), as defined by the presence of a lesion that does not allow passage of a diagnostic adult upper endoscope (eg, with an insertion tube diameter of >9mm). Subject is on a pure liquid diet or the six-food elimination diet. Subject has presence of esophageal varices at the EGD at the final treatment evaluation visit (Visit 4) of the SHP621-301 study. Subject has any current disease of the gastrointestinal tract, aside from EoE, including eosinophilic gastritis, enteritis, colitis, or proctitis, inflammatory bowel disease, or celiac disease. Subject has other diseases causing or associated with esophageal eosinophilia, including hypereosinophilic syndrome, collagen vascular disease, vasculitis, achalasia, or parasitic infection. Subject has oropharyngeal or esophageal candidiasis that failed to respond to previous treatment. Diagnosis with oropharyngeal or esophageal candidiasis at or since the final treatment evaluation visit (Visit 4) of the SHP621-301 study is not an exclusion as long as the subject received treatment for candidiasis and is expected to respond to treatment. Subject has acute or chronic infection or immunodeficiency condition, including tuberculosis, fungal, bacterial, viral/parasite infection, ocular herpes simplex, or chicken pox/measles. Subject has upper gastrointestinal bleeding identified in the EGD at the final treatment evaluation visit (Visit 4) of the SHP621-301 study or since the final treatment evaluation visit (Visit 4) of the SHP621-301 study. Subject has evidence of active infection with Helicobacter pylori. Subject has evidence of unstable asthma since the final treatment evaluation visit (Visit 4) of the SHP621-301 study. Subject is female and pregnant or nursing. Subject has a history of intolerance, hypersensitivity, or idiosyncratic reaction to budesonide (or any other corticosteroids), or to any other ingredients of the study medication. Subject has a history or high risk of noncompliance with treatment or regular clinic visits. Subject is on sucralfate or anticipates using sucralfate during the treatment period.
Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 55 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
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No
Study Plan
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How is the study designed?
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Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arms A OBS Completers/ Responders<br>Arm A Oral Budesonide Suspension Completers/ Responders | Drug: Oral Budesonide Suspension (OBS)<br>* OBS 2mg twice daily<br>|
| Placebo Comparator: Arm B OBS Completers/ Responders<br>Arm B Oral Budesonide Suspension Completers/ Responders. 1:1 randomization for Arms A and B | Drug: Placebo<br>* Matching Placebo dose<br>|
| Experimental: Arm C OBS Completers/ Non-Responders<br>Arm C Oral Budesonide Suspension Completers/ Non-Responders | Drug: Oral Budesonide Suspension (OBS)<br>* OBS 2mg twice daily<br>|
| Experimental: Arm D Placebo Completers<br>Arm D Placebo Completers | Drug: Oral Budesonide Suspension (OBS)<br>* OBS 2mg twice daily<br>|
What is the study measuring?
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Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Who Had Relapse During the Entire Week 36 Period | Relapse (Yes/No) was defined as meeting both the eosinophil histology relapse criterion and the dysphagia symptom relapse criterion. Eosinophil histology relapse was defined as an eosinophil count of greater than or equal to(> or =) 15 per high-power field (eos/hpf) from at least 2 of 3 levels of the esophagus. Dysphagia symptom relapse was defined as having at least 4 days of dysphagia (with answer 'Yes' for question 2 in DSQ [Dysphagia Symptom Questionnaire]) in the 2-week period prior to the scheduled visit, as determined by the DSQ. | Week 36 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Long-term Treatment Response From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | Long-term response from SHP621-301 baseline defined: histologic response,defined as peak eosinophil count of less than or equal to(< or =)6/HPF across all available esophageal levels at Week 36 and Dysphagia symptom response 1,defined as >or= 30 percent(%) reduction in DSQ combined score(Questions [Q] 2+3) from baseline of SHP621-301 to Week 36.DSQcontain 4 questions,all participants used diary,responded to Q1(didyoueatsolid food),Q2(did food pass slowly or get stuck). If participant's answer to Q2 was No,diary ended for day. If participant answered Yes,he/she advanced to Q3(didyouhavetodoanything to make food go downorget relief), Q4(extent to which participant experienced pain while swallowing).DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/Number of diaries reported with non-missing data.Scale range was0-2 forQ2 and 0-4 forQ 3.Scale range for DSQ combined score was 0-84.Highervaluesrepresentingworseoutcome.Negative change from baseline indicates symptoms decreased. | Week 36 |
| Proportion of Participants With Long-term Treatment Response From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | Long-term response from baseline defined: histologic response, defined as peak eosinophil count of less than or equal to(< or =) 6/HPF across all available esophageal levels at Week 36 and Dysphagia symptom response 1,defined as >or= 30 percent(%) reduction in DSQ combined score (Questions [Q] 2+3) from baseline of SHP621-301 to Week 36.DSQcontain 4 questions,all participants used diary,responded to Q1(did you eat solid food),Q2(did food pass slowly or get stuck). If participant's answer to Q2 was No,diary ended for day. If participant answered Yes,he/she advanced to Q3(didyouhavetodoanything to make food go downorget relief), Q4(extent to which participant experienced pain while swallowing).DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/Number of diaries reported with non-missing data.Scale range was0-2 forQ2 and 0-4 forQ 3.Scale range for DSQ combined score was 0-84. Higher values representing worse outcome.Negative change from baseline indicates symptoms decreased. | Week 36 |
| Proportion of Participants Who Had a Histologic Response (Eosinophil Count of Less Than or Equal to (<or=6)/High-Powered Field [HPF]) at Week 12 and Week 36 | Histology response was defined as a peak eosinophil count of <or=6/HPF across all available levels at Week 12 and Week 36. | Week 12 and Week 36 |
| Proportion of Participants Who Had at Least a 30 Percent (%) Change in DSQ Combined Score From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 12 and Week 36 | Dysphagia symptom response with respect to the baseline of induction study (SHP621-301 [NCT02605837]) was defined as 30% reduction in DSQ combined score (questions 2+3) at Week 12 and Week 36 of current study from baseline of the induction study. DSQ contain 4 questions, all participants used a diary and responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was No, then diary ended for that day. If participant answered Yes,he/she advanced to Q3 (did you have to do anything to make food go down or get relief) and Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3. Scale range for DSQ combined score was 0-84. Higher values representing worse outcome. Negative change from baseline indicates symptoms decreased. | Baseline of SHP621-301 (NCT02605837), Week 12 and Week 36 |
| Proportion of Participants Who Had at Least a 30 Percent (%) Change in DSQ Combined Score From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36 | Dysphagia symptom response with respect to the baseline of current study (SHP621-302 [NCT02736409]) was defined as 30% reduction in DSQ combined score (questions 2+3) at Week 12 and Week 36 from baseline of the current study. DSQ contain 4 questions, all participants used diary and responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was No, then diary ended for that day. If participant answered Yes,he/she advanced to Q3 (did you have to do anything to make food go down or get relief) and Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q 3. Scale range for DSQ combined score was 0-84. Higher values representing a worse outcome. A Negative change from baseline indicates symptoms decreased. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36 |
| Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Total Endoscopy Score at Week 12 and Week 36 of Current Study | Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 categories: 1) exudates or plaques (grade 0-2); 2) fixed esophageal rings (grade 0-3); 3) edema (grade 0-2); 4) furrows (grade 0-2); and 5) strictures (grade 0-1). An endoscopy score for each category was calculated and summed for each anatomic location (proximal and distal). The minimum and maximum endoscopy score was 0 and 10 points respectively for each location (proximal and distal) and the total endoscopy score was the sum of the scores for the proximal and distal locations (maximum total score of 20 points respectively). The higher score indicated worse appearance. A negative change from baseline indicates that appearance improved. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36 |
| Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Total Endoscopy Score at Week 12 and Week 36 | Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 categories: 1) exudates or plaques (grade 0-2); 2) fixed esophageal rings (grade 0-3); 3) edema (grade 0-2); 4) furrows (grade 0-2); and 5) strictures (grade 0-1). An endoscopy score for each category was calculated and summed for each anatomic location (proximal and distal). The minimum and maximum endoscopy score was 0 and 10 points respectively for each location (proximal and distal) and the total endoscopy score was the sum of the scores for the proximal and distal locations (maximum total score of 20 points respectively). The higher score indicated worse appearance. A negative change from baseline indicates that appearance improved. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36 |
| Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Peak Eosinophil Count at Week 12 and Week 36 of Current Study | Change from induction study (SHP621-301 [NCT02605837]) baseline in peak eosinophil count at Week 12 and Week 36 of current study was reported. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36 |
| Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Peak Eosinophil Count at Week 12 and Week 36 | Change from current study (SHP621-302 [NCT02736409]) baseline in peak eosinophil count at Week 12 and Week 36 was reported. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36 |
| Proportion of Participants Who Had Peak Eosinophil Count Less Than (<) 15/High-Powered Field (HPF) at Week 12 and Week 36 | Proportion of participants who had Peak Eosinophil Count less than (<) 15/HPF at Week 12 and Week 36 were reported. | Week 12 and Week 36 |
| Proportion of Participants Who Had Peak Eosinophil Count Less Than or Equal to (< or =) 1/High-Powered Field (HPF) at Week 12 and Week 36 | Proportion of participants who had Peak Eosinophil Count less than or equal to (< or =) 1/High-Powered Field (HPF) at Week 12 and Week 36 were reported. | Week 12 and Week 36 |
| Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in Peak Eosinophil Count for Each Available Esophageal Level (Proximal, Mid, and Distal) at Week 12 and Week 36 of Current Study | Change from induction study (SHP621-301 [NCT02605837]) baseline in peak eosinophil count for each available esophageal level (proximal, mid, distal) at Week 12 and Week 36 of current study were reported. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36 |
| Change From Current Study (SHP621-302 [NCT02736409]) Baseline in Peak Eosinophil Count for Each Available Esophageal Level (Proximal, Mid, and Distal) at Week 12 and Week 36 | Change from current study (SHP621-302 [NCT02736409]) baseline in peak eosinophil count for each available esophageal level (proximal, mid, distal) at Week 12 and Week 36 were reported. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36 |
| Change From Induction Study (SHP621-301 [NCT02605837]) Baseline in the Histopathologic Epithelial Features Combined Total Score (Grade and Stage) at Week 12 an Week 36 of Current Study | Eight histopathologic epithelial features (basal layer hyperplasia, eosinophil peak, abscesses, surface layering, dilated intercellular spaces, surface alteration, dyskeratotic epithelial cells, lamina propria fibrosis) are scored on a 4-point scale (0=normal, 3=worst) for both the severity of the abnormality (i.e., grade) and the amount of tissue affected by the abnormality (i.e. stage). Thus each of the 3 levels had a minimum score of 0 and maximum possible score of 24, and a possible total grade or stage score of 72 for a maximum combined score of 144. Combined total score ratio (TSR) =(proximal TSR + mid TSR + distal TSR)/N, where N is the number of non missing sections for TSR. A negative change from baseline indicates that epithelial inflammation decreased. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 12 and Week 36 |
| Change From Current Study (SHP621-302 [NCT02736409]) Baseline in the Histopathologic Epithelial Features Combined Total Score (Grade and Stage) at Week 12 and Week 36 | Eight histopathologic epithelial features (basal layer hyperplasia, eosinophil peak, abscesses, surface layering, dilated intercellular spaces, surface alteration, dyskeratotic epithelial cells, lamina propria fibrosis) are scored on a 4-point scale (0=normal, 3=worst) for both the severity of the abnormality (i.e., grade) and the amount of tissue affected by the abnormality (i.e. stage). Thus each of the 3 levels had a minimum score of 0 and maximum possible score of 24, and a possible total grade or stage score of 72 for a maximum combined score of 144. Combined total score ratio (TSR) =(proximal TSR + mid TSR + distal TSR)/N, where N is the number of non missing sections for TSR. A negative change from baseline indicates that epithelial inflammation decreased. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 12 and Week 36 |
| Proportion of Participants Who Had Greater Than or Equal to (>or=) 50 Percent (%) Reduction in DSQ Combined Score From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 12 and Week 36 | Dysphagia symptom response from the baseline of SHP621-301, was defined as >or=50% reduction in DSQ combined score (questions [Q] 2+3) from baseline of the induction study at Week 12 and 36 of current study. DSQ contained 4Q, all participants used diary, and responded to Q1(did you eat solid food) and Q2(didfood passslowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If a participant answered 'Yes', he/she advanced to Q3(did you have to do anything to make food go down or get relief) and 4(extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0-84, with higher values representing a worse outcome. Anegative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Proportion of Participants Who Had Greater Than or Equal to (>or=) 50 Percent (%) Reduction in DSQ Combined Score From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36 | Dysphagia symptom response from the baseline of SHP621-302, was defined as >or=50% reduction in DSQ combined score (questions 2+3) from baseline of the induction study at Week 36 of current study. DSQ contained 4Q, all participants used diary, and responded to Q1 (did you eat solid food) and Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If a participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make food go down or get relief) and 4(extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0-84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Change in the DSQ Combined Score (Questions 2+3) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | DSQ contain 4 questions (Q), all participants used a diary, responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make food go down or get relief), Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3. Scale range for DSQ combined score was 0-84. Higher values representing a worse outcome. A Negative change from baseline indicates symptoms decreased. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Change in the DSQ Combined Score (Questions 2+3) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | DSQ contain 4 questions, all participants used a diary, responded to Q1 (did you eat solid food), Q2 (did food pass slowly or get stuck). If participant's answer to Q2 was 'No', then diary ended for that day. If participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make food go down or get relief), Q4 (extent to which participant experienced pain while swallowing). DSQ combined score= ([sum of points from Q2+3 in daily DSQ] × 14)/Number of diaries reported with non-missing data. Scale range was 0-2 for Q2 and 0-4 for Q3. Scale range for DSQ combined score was 0-84. Higher values representing a worse outcome. A Negative change from baseline indicates symptoms decreased. Change in DSQ combined score (Questions 2+3) from baseline of current study at Week 36 was reported. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
| Percent Change in the DSQ Combined Score (Questions 2+3) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | Percent change in DSQ combined score from Induction Study (SHP621-301 [NCT02605837]) baseline to current study (SHP621-302 [NCT02736409]) final treatment period (Week 36) was reported. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Percent Change in the DSQ Combined Score (Questions 2+3) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | Percent change in DSQ combined score from baseline to final treatment period (Week 36) of current study was reported. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
| Proportion of Participants Who Had Overall Binary Response I From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 12 and Week 36 of Current Study | Overall binary response I was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 30% reduction in DSQ combined score from baseline of the induction study (SHP621-301 [NCT02605837]) at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Proportion of Participants Who Had Overall Binary Response I From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36 | Overall binary response I was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 30% reduction in DSQ combined score from baseline at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Proportion of Participants Who Had Overall Binary Response II From Induction Study SHP621-301 (NCT02605837) Baseline at Week 12 and Week 36 of Current Study | Overall binary response II was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 50% reduction in DSQ combined score from baseline of the SHP621-301 study at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Proportion of Participants Who Had Overall Binary Response II From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 12 and Week 36 | Overall binary response II was defined as if participant had peak eosinophil count of <=6/HPF across all esophagus levels and achieved a minimum of 30% reduction in DSQ combined score from baseline at Week 12 and Week 36. DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Week 12 and Week 36 |
| Change in the DSQ + Pain Score (Questions 2+3+4) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ + pain score was calculated by summing the scores of responses to questions 2, 3, and 4 by using following formula: DSQ + pain score= ([sum of points from questions 2+3+4 in the daily DSQ] ×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2, 0 - 4 for question 3 and 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ + pain score was 0 - 140, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Change in the DSQ+ Pain Score (Questions 2+3+4) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | DSQ contained 4 questions, all participants used a diary, and responded to Questions (Q) 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Q2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Q3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ + pain score was calculated by summing the scores of responses to Questions 2, 3, and 4. Question 1 was excluded from the DSQ + pain score. DSQ + pain score=(Sum of points from questions 2+3+4 in the daily DSQ)*14 Days/Number of dairies reported with non-missing data. Scale range was 0 - 2 for Q2, 0 - 4 for Q3 and 0 - 4 for Q4, with higher values representing a worse outcome. Scale range for DSQ + pain score was 0 - 140, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
| Change in the DSQ Pain Score (Question 4) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ pain score was calculated by summing the scores of responses to Question 4 only. DSQ pain score=(sum of points from questions 4 in the daily DSQ)*14 days/Number of diaries reported with non-missing data. Scale range was 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ pain score was 0 - 56, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Change in the DSQ Pain Score (Question 4) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ pain score was calculated by summing the scores of responses to Question 4 only. DSQ pain score=(sum of points from questions 4 in the daily DSQ)*14 days/Number of diaries reported with non-missing data. Scale range was 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ pain score was 0 - 56, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
| Number of Participants With Treatment Emergent Adverse Events (TEAE's) | An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started or deteriorated on or after the date of the first dose of double-blind IP in SHP621-302 and through the safety follow-up contact, or 31 days after the last dose of IP for participants who did not have a safety follow-up contact. | From start of the study drug administration up to follow up (Week 40) |
| Change in DXA (Dual-Energy X-ray Absorptiometry) Imaging Results (Location: Lumbar Spine [L1-L4]) From Induction Study (SHP621-301 [NCT02605837]) Baseline at Week 36 of Current Study | The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Baseline of SHP621-301 is determined at Week 0 in the SHP621-301 study. Here in this outcome measure DXA measurement of L1-L4 were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Change in DXA Imaging Results (Location: Lumbar Spine [L1-L4]) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Here in this outcome measure DXA measurement of L1-L4 were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
| Change in DXA Imaging Results (Location: Whole Body) From Baseline of Induction Study (SHP621-301 [NCT02605837]) at Week 36 of Current Study | The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Baseline of SHP621-301 is determined at Week 0 in the SHP621-301 study. Here in this outcome measure DXA measurement of whole body (except head) were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. | Baseline of induction study (SHP621-301 [NCT02605837]), Week 36 |
| Change in DXA Imaging Results (Location: Whole Body) From Current Study (SHP621-302 [NCT02736409]) Baseline at Week 36 | The sites for DXA measurement were the lumber spine (L1-L4 preferred) and total body less head. DXA scans for bone mineral density (BMD) and body composition measurements were done only for adolescent participants aged 11-17 years based on the age group in the SHP621-301 study and were completed throughout the SHP621-302 study even if participants turned 18 years. Here in this outcome measure DXA measurement of whole body (except head) were reported. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. A Z-score of 0 is equal to the mean. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. | Baseline of Current Study (SHP621-302 [NCT02736409]), Week 36 |
|
||
NCT00446901
|
Selenium and Prostate Cancer: Clinical Trial on Availability to Prostate Tissue and Effects on Gene Expression
|
The aim of this study is to determine whether selenium supplementation leads to changes in selenium levels and gene expression profiles in prostate tissue.
|
Rationale: Prostate cancer is a frequently observed malignancy in men, especially in elderly men. Besides diagnosis and treatment, also prevention of prostate cancer is an important point of interest to reduce the incidence and mortality of prostate cancer. Selenium is considered to be a promising chemopreventive agent for prostate cancer. Exact mechanisms of chemoprevention by selenium are not fully understood. However, it is expected that selenium (among other effects) directly affects gene expression in the prostate.~Objective: The aim of this study is to get insight into bioavailability of selenium in prostate tissue and changes of gene expression profiles that might be responsible for selenium-induced chemoprevention. To meet this objective, the relationship between dietary selenium intake and changes in gene expression profiles, tissue selenium levels and blood flow in prostate tissue will be examined.~Study design: The present study is designed as a double-blind, randomized and placebo-controlled intervention trial. Blood samples, toenails, questionnaires, MR images and surgical specimens will be collected to examine effects of selenium supplementation.~Study population: The study population will consist of 60 men, diagnosed with prostate cancer and scheduled for radical prostatectomy. Written informed consent will be obtained from each participant.~Intervention: Participants will receive 300 ug selenium / day or a placebo during 5 weeks prior to radical prostatectomy. Selenium will be supplemented in the form of selenized yeast tablets (SelenoPrecise, Pharma Nord).~Main study parameters: Levels of selenium in prostate tissue and changes in prostate gene expression profiles of participants supplemented with selenium or placebo, compared before and after the short intervention period, will be considered as the main parameters of the present study. Besides gene expression profiles in prostate tissue, also gene expression profiles of peripheral mononuclear cells (PBMC), levels of selenium in blood and toenails and blood flow and permeability of blood vessels of prostate tissue will be analyzed.
|
Selenium and Prostate Cancer: Clinical Trial on Availability to Prostate Tissue and Effects on Gene Expression
|
Prostatic Neoplasms, Prostate Cancer
|
* Dietary Supplement: Selenium
|
Inclusion Criteria:~male~biopsy proven prostate cancer~scheduled for radical prostatectomy~Exclusion Criteria:~liver diseases (e.g. hepatitis)~kidney diseases~inflammatory bowel diseases~use of dietary supplements containing selenium~adjuvant therapy for prostate cancer (e.g. hormonal therapy, HIFU)~previously or concurrent diagnosed with cancer, other than prostate cancer
| null | null |
Male
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| selenium levels in prostate tissue | | after 5 weeks of intervention with selenium or placebo |
| changes in gene expression profiles in prostate tissue | | after 5 weeks of intervention with selenium or placebo |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in blood flow, vessel permeability and exocrine functionality | | after 5 weeks of intervention with selenium or placebo |
| changes in gene expression profiles in blood cells | | after 5 weeks of intervention with selenium or placebo |
|
Prostate Cancer, Selenium, Chemoprevention, Gene expression
|
Selenium, Antioxidants, Molecular Mechanisms of Pharmacological Action, Protective Agents, Physiological Effects of Drugs, Trace Elements, Micronutrients
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Dietary Supplement: Selenium<br>* Selenized yeast, 300 ug/day<br>* Other names: SelenoPrecise, PharmaNord;|
| Experimental: Selenium (selenized yeast)<br>Selenium (selenized yeast) tablets, 300 ug/day | Dietary Supplement: Selenium<br>* Selenized yeast, 300 ug/day<br>* Other names: SelenoPrecise, PharmaNord;|
|
Selenium and Prostate Cancer: Clinical Trial on Availability to Prostate Tissue and Effects on Gene Expression
Study Overview
=================
Brief Summary
-----------------
The aim of this study is to determine whether selenium supplementation leads to changes in selenium levels and gene expression profiles in prostate tissue.
Detailed Description
-----------------
Rationale: Prostate cancer is a frequently observed malignancy in men, especially in elderly men. Besides diagnosis and treatment, also prevention of prostate cancer is an important point of interest to reduce the incidence and mortality of prostate cancer. Selenium is considered to be a promising chemopreventive agent for prostate cancer. Exact mechanisms of chemoprevention by selenium are not fully understood. However, it is expected that selenium (among other effects) directly affects gene expression in the prostate. Objective: The aim of this study is to get insight into bioavailability of selenium in prostate tissue and changes of gene expression profiles that might be responsible for selenium-induced chemoprevention. To meet this objective, the relationship between dietary selenium intake and changes in gene expression profiles, tissue selenium levels and blood flow in prostate tissue will be examined. Study design: The present study is designed as a double-blind, randomized and placebo-controlled intervention trial. Blood samples, toenails, questionnaires, MR images and surgical specimens will be collected to examine effects of selenium supplementation. Study population: The study population will consist of 60 men, diagnosed with prostate cancer and scheduled for radical prostatectomy. Written informed consent will be obtained from each participant. Intervention: Participants will receive 300 ug selenium / day or a placebo during 5 weeks prior to radical prostatectomy. Selenium will be supplemented in the form of selenized yeast tablets (SelenoPrecise, Pharma Nord). Main study parameters: Levels of selenium in prostate tissue and changes in prostate gene expression profiles of participants supplemented with selenium or placebo, compared before and after the short intervention period, will be considered as the main parameters of the present study. Besides gene expression profiles in prostate tissue, also gene expression profiles of peripheral mononuclear cells (PBMC), levels of selenium in blood and toenails and blood flow and permeability of blood vessels of prostate tissue will be analyzed.
Official Title
-----------------
Selenium and Prostate Cancer: Clinical Trial on Availability to Prostate Tissue and Effects on Gene Expression
Conditions
-----------------
Prostatic Neoplasms, Prostate Cancer
Intervention / Treatment
-----------------
* Dietary Supplement: Selenium
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: male biopsy proven prostate cancer scheduled for radical prostatectomy Exclusion Criteria: liver diseases (e.g. hepatitis) kidney diseases inflammatory bowel diseases use of dietary supplements containing selenium adjuvant therapy for prostate cancer (e.g. hormonal therapy, HIFU) previously or concurrent diagnosed with cancer, other than prostate cancer
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
No
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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Dietary Supplement: Selenium<br>* Selenized yeast, 300 ug/day<br>* Other names: SelenoPrecise, PharmaNord;|
| Experimental: Selenium (selenized yeast)<br>Selenium (selenized yeast) tablets, 300 ug/day | Dietary Supplement: Selenium<br>* Selenized yeast, 300 ug/day<br>* Other names: SelenoPrecise, PharmaNord;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| selenium levels in prostate tissue | | after 5 weeks of intervention with selenium or placebo |
| changes in gene expression profiles in prostate tissue | | after 5 weeks of intervention with selenium or placebo |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in blood flow, vessel permeability and exocrine functionality | | after 5 weeks of intervention with selenium or placebo |
| changes in gene expression profiles in blood cells | | after 5 weeks of intervention with selenium or placebo |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prostate Cancer, Selenium, Chemoprevention, Gene expression
|
NCT03165643
|
The DNA Methylation of ARHGEF11 in Macrosomia
|
Background Macrosomia at birth is associated with subsequent susceptibility to obesity, abnormal glucose metabolism, hypertension and dyslipidaemia. Epigenetic reprogramming has been reported to be involved in the development of human diseases caused by suboptimal environmental or nutritional factors.~Objective The study was aiming to explore epigenetic mechanism influences on macrosomic infants exposed to intrauterine hyperglycemia.~Design The investigators performed a genome-wide analysis of DNA methylation in cord blood from macrosomic infants born to women with gestational diabetes or infants with normal birth weight born to normal glucose-tolerant women in order to identify genes related to foetal growth or early adipose tissue development. The candidate genes were then validated using SEQUENOM MassARRAY after bisulfite conversion.
|
Epigenetic Alteration of Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) in Cord Blood Samples in Macrosomia Exposed to Intrauterine Hyperglycaemia
|
Gestational Diabetes, Diabetes, Macrosomia, Fetal
|
* Diagnostic Test: OGTT
|
Inclusion Criteria:~-~Exclusion Criteria:~Pregnancies complicating with hypertensive disorders, pre-gestational diabetes, thyroid diseases, renal dysfunction were excluded.
| null | null |
Female
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GDM was identified | According to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria, gestational diabetes mellitus (GDM) was diagnosed when at least one cut point was reached in 2-hour 75-g OGTT test: a fasting plasma glucose (FPG) ≥ 5.1 mmol/L (92 mg/dL), a 1-hour ≥ 10.0 mmol/L (180 mg/dL) or a 2-hour ≥ 8.5 mmol/L (153 mg/dL). Participants were divided into two groups based on OGTT: Group normal glucose tolerant (NGT, n=132) and Group GDM (n=107). | 24-28 weeks |
| Foetal macrosomia was identified | After delivery, participants were further divided into four subgroups based on neonatal birth weight: normal birth weight (NBW) was defined as 2500g ≤ birth weight < 4000g, macrosomia (Mac) was defined as birth weight ≥ 4000g. Group NGT-NBW (n=83): normal glucose tolerant women with normal neonatal birth weight; Group NGT-Mac (n=49): normal glucose tolerant women with macrosomia; Group GDM-NBW (n=82): GDM women with normal neonatal birth weight; Group GDM-Mac (n=25): GDM women with macrosomia. | 40 weeks |
| DNA methylation level in macrosomia | Investigators performed a genome-wide analysis of DNA methylation in cord blood from macrosomic infants born to women with gestational diabetes or infants with normal birth weight born to normal glucose-tolerant women in order to identify genes related to foetal growth or early adipose tissue development. The candidate genes were then validated using SEQUENOM MassARRAY after bisulfite conversion. | 40 weeks |
|
Diabetes, Gestational, Fetal Macrosomia, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Fetal Diseases, Pregnancy in Diabetics, Diabetes Complications, Birth Weight, Body Weight
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NGT-normal birth weight<br> | |
| NGT-macrosomia<br> | |
| GDM-normal birth weight<br> | Diagnostic Test: OGTT<br>* 75 g glucose tolerance test was provided to all pregnant women during 24-28 weeks.<br>|
| GDM-macrosomia<br> | Diagnostic Test: OGTT<br>* 75 g glucose tolerance test was provided to all pregnant women during 24-28 weeks.<br>|
|
The DNA Methylation of ARHGEF11 in Macrosomia
Study Overview
=================
Brief Summary
-----------------
Background Macrosomia at birth is associated with subsequent susceptibility to obesity, abnormal glucose metabolism, hypertension and dyslipidaemia. Epigenetic reprogramming has been reported to be involved in the development of human diseases caused by suboptimal environmental or nutritional factors. Objective The study was aiming to explore epigenetic mechanism influences on macrosomic infants exposed to intrauterine hyperglycemia. Design The investigators performed a genome-wide analysis of DNA methylation in cord blood from macrosomic infants born to women with gestational diabetes or infants with normal birth weight born to normal glucose-tolerant women in order to identify genes related to foetal growth or early adipose tissue development. The candidate genes were then validated using SEQUENOM MassARRAY after bisulfite conversion.
Official Title
-----------------
Epigenetic Alteration of Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) in Cord Blood Samples in Macrosomia Exposed to Intrauterine Hyperglycaemia
Conditions
-----------------
Gestational Diabetes, Diabetes, Macrosomia, Fetal
Intervention / Treatment
-----------------
* Diagnostic Test: OGTT
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Exclusion Criteria: Pregnancies complicating with hypertensive disorders, pre-gestational diabetes, thyroid diseases, renal dysfunction were excluded.
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NGT-normal birth weight<br> | |
| NGT-macrosomia<br> | |
| GDM-normal birth weight<br> | Diagnostic Test: OGTT<br>* 75 g glucose tolerance test was provided to all pregnant women during 24-28 weeks.<br>|
| GDM-macrosomia<br> | Diagnostic Test: OGTT<br>* 75 g glucose tolerance test was provided to all pregnant women during 24-28 weeks.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GDM was identified | According to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria, gestational diabetes mellitus (GDM) was diagnosed when at least one cut point was reached in 2-hour 75-g OGTT test: a fasting plasma glucose (FPG) ≥ 5.1 mmol/L (92 mg/dL), a 1-hour ≥ 10.0 mmol/L (180 mg/dL) or a 2-hour ≥ 8.5 mmol/L (153 mg/dL). Participants were divided into two groups based on OGTT: Group normal glucose tolerant (NGT, n=132) and Group GDM (n=107). | 24-28 weeks |
| Foetal macrosomia was identified | After delivery, participants were further divided into four subgroups based on neonatal birth weight: normal birth weight (NBW) was defined as 2500g ≤ birth weight < 4000g, macrosomia (Mac) was defined as birth weight ≥ 4000g. Group NGT-NBW (n=83): normal glucose tolerant women with normal neonatal birth weight; Group NGT-Mac (n=49): normal glucose tolerant women with macrosomia; Group GDM-NBW (n=82): GDM women with normal neonatal birth weight; Group GDM-Mac (n=25): GDM women with macrosomia. | 40 weeks |
| DNA methylation level in macrosomia | Investigators performed a genome-wide analysis of DNA methylation in cord blood from macrosomic infants born to women with gestational diabetes or infants with normal birth weight born to normal glucose-tolerant women in order to identify genes related to foetal growth or early adipose tissue development. The candidate genes were then validated using SEQUENOM MassARRAY after bisulfite conversion. | 40 weeks |
|
||||
NCT01466920
|
Why Are so Many Patients Dissatisfied With Knee Replacement Surgery? Exploring Variations of the Patient Experience
|
The goal of this research is to fill the knowledge gap relating to why up to 20 percent of total knee arthroplasty (TKA) patients are dissatisfied with their clinical outcomes and to answer the research question: What are the drivers of variation in the patient experience with primary (ie. not revision) TKA?
|
Purpose: Among patients with a diagnosis of osteoarthritis and who are undergoing total knee arthroplasty:~To identify variations in the patient experience with primary knee replacement surgery by measuring clinical outcomes, health status, and patient satisfaction; and~To explore the factors contributing to good/poor clinical and patient outcomes, such as surgical factors, health system factors, socioeconomic demographic factors and psychological factors.
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Why Are so Many Patients Dissatisfied With Knee Replacement Surgery? Exploring Variations of the Patient Experience
|
Total Knee Arthroplasty
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Inclusion Criteria:~Adults 19 and older~Primary or secondary diagnosis of osteoarthritis or inflammatory arthritis~Scheduled to undergo primary TKA~Living in British Columbia~Capable of providing informed consent~Exclusion Criteria:~Not having been diagnosed with osteoarthritis~Inability to complete the study questionnaires~Adults undergoing arthroplasty revision surgery~Adults undergoing bilateral knee replacements~Adults undergoing unicompartmental knee replacements~Adults whose knee replacement is due to post-traumatic deformity Contacts and Locations
|
19 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
Total knee arthroplasty
|
Why Are so Many Patients Dissatisfied With Knee Replacement Surgery? Exploring Variations of the Patient Experience
Study Overview
=================
Brief Summary
-----------------
The goal of this research is to fill the knowledge gap relating to why up to 20 percent of total knee arthroplasty (TKA) patients are dissatisfied with their clinical outcomes and to answer the research question: What are the drivers of variation in the patient experience with primary (ie. not revision) TKA?
Detailed Description
-----------------
Purpose: Among patients with a diagnosis of osteoarthritis and who are undergoing total knee arthroplasty: To identify variations in the patient experience with primary knee replacement surgery by measuring clinical outcomes, health status, and patient satisfaction; and To explore the factors contributing to good/poor clinical and patient outcomes, such as surgical factors, health system factors, socioeconomic demographic factors and psychological factors.
Official Title
-----------------
Why Are so Many Patients Dissatisfied With Knee Replacement Surgery? Exploring Variations of the Patient Experience
Conditions
-----------------
Total Knee Arthroplasty
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults 19 and older Primary or secondary diagnosis of osteoarthritis or inflammatory arthritis Scheduled to undergo primary TKA Living in British Columbia Capable of providing informed consent Exclusion Criteria: Not having been diagnosed with osteoarthritis Inability to complete the study questionnaires Adults undergoing arthroplasty revision surgery Adults undergoing bilateral knee replacements Adults undergoing unicompartmental knee replacements Adults whose knee replacement is due to post-traumatic deformity Contacts and Locations
Ages Eligible for Study
-----------------
Minimum Age: 19 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 |
| --- | --- | --- |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Total knee arthroplasty
|
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NCT01933893
|
Follicular Versus Luteal Pipelle in Repeated Implantation Failure Patients
|
Pipelle was found to increase pregnancy and implantation rates in women undergoing IVF treatment in general, and in particular in repeated implantation failure (RIF). However, there is virtually no data regarding the optimal timing for the pipelle.~The current study aims to compare between follicular and luteal pipelle on pregnancy rate in RIF patients.
| null |
Repeated Implantation Failure
|
Inclusion Criteria:~Women diagnosed with RIF who are going to start a new IVF treatment~Exclusion Criteria:~Known hydrosalpinx body mass index (BMI) >29 kg/m2 or <18 kg/m2 Low ovarian response
|
18 Years
|
40 Years
|
Female
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy rate | | April, 2014 |
|
Pipelle, luteal, follicular, implantation
|
Follicular Versus Luteal Pipelle in Repeated Implantation Failure Patients
Study Overview
=================
Brief Summary
-----------------
Pipelle was found to increase pregnancy and implantation rates in women undergoing IVF treatment in general, and in particular in repeated implantation failure (RIF). However, there is virtually no data regarding the optimal timing for the pipelle. The current study aims to compare between follicular and luteal pipelle on pregnancy rate in RIF patients.
Conditions
-----------------
Repeated Implantation Failure
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women diagnosed with RIF who are going to start a new IVF treatment Exclusion Criteria: Known hydrosalpinx body mass index (BMI) >29 kg/m2 or <18 kg/m2 Low ovarian response
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years
Sexes Eligible for Study
-----------------
Female
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 |
| --- | --- | --- |
| Pregnancy rate | | April, 2014 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pipelle, luteal, follicular, implantation
|
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NCT02398799
|
Supporting Dyads Affected by Heart Failure
|
The aim of this randomized controlled trial was to evaluate the effects of an integrated dyad care program with education and psychosocial support to patients with chronic heart failure and their partners during a post-discharge period after acute deterioration of heart failure.~Methods: One hundred fifty five patient-caregiver dyads has been randomized to usual care or a psycho-education intervention delivered in three modules through nurse-led face-to-face counseling, computer-based education and other written teaching materials to assist dyads develop problem-solving skills. Follow-up assessments has been completed after 3, 12 and 24 months to assess perceived control, perceived health, depressive symptoms, self-care, knowledge, caregiver burden and health care utilization.
|
Heart failure is a serious condition with a poor prognosis. It is the leading cause of hospitalization and readmissions for worsening heart failure remains high. Treatment aims to reduce symptoms and morbidity and to improve quality of life and survival. Counseling and education is an important part of treatment, but despite the fact that most patients receive education, many are not able to adequately engage in self-care activities. Non-adherence to self-care recommendations is high which may be a contributing factor for worsening heart failure and to the high number of readmissions.~Having support of a partner is important for patients with heart failure. Supportive others have the potential to improve self-care outcomes and increase adherence to treatment. At the same time, it should be acknowledged that the disease can also affect the partners negatively. However, emotional reactions of burden and stress decrease when partner's experiences control over the heart disease.~Despite the fact that heart failure has a number of negative consequences for patients and the partners, research addressing self-care barriers from a family perspective is rare, and until now contemporary care has remained patient focused. Previous studies have indicated the importance of partner support but have not found the appropriate methods for involving and encourage partners. Therefore, studies focusing on the heart failure patient-partner dyad are needed, but to date, most studies have only evaluated short term effects of intervention programs, while long term effects might be of equally importance. The aim of this randomized controlled study was to evaluate the effects of an integrated dyad care program with education and psychosocial support to patients with chronic heart failure and their partners during a post-discharge period after acute deterioration of heart failure.~Methods: One hundred fifty five patient-caregiver dyads has been randomized to usual care (n = 71) or a psycho-education intervention (n = 84) delivered in three modules through nurse-led face-to-face counseling, computer-based education and other written teaching materials to assist dyads develop problem-solving skills. Follow-up assessments has been completed after 3, 12 and 24 months to assess perceived control, perceived health, depressive symptoms, self-care, knowledge, caregiver burden and health care utilization.
|
Supporting Dyads Affected by Heart Failure - A Randomised Controlled Study Evaluating a Psychoeducational Intervention
|
Heart Failure
|
* Behavioral: Psychoeducational support
|
Inclusion Criteria:~The inclusion criteria were to be a dyad consisting of a patient diagnosed with heart failure based on the European Society of Cardiology guidelines,~New York Heart Association (NYHA) class II-IV,~with a partner living in the same household as the patient,~recently discharged from hospital (i.e. 2-3 weeks) following a heart failure acute exacerbation.~Exclusion Criteria:~Exclusion criteria for the dyads were dementia, or other severe psychiatric illnesses,~drug abuse,~difficulties in understanding or reading the Swedish language,~undergoing cardiac surgery including cardiac transplant or~participating in other studies.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perceived control measure by Control Attitude Scale | Perceived control in patients and partners | 3 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life measure by SF-36 | Quality of life in patients and partners | 3, 12 and 24 months |
| Self care measured by European Self-care Behaviour Scale | Self care in patients | 3, 12 and 24 months |
| Caregiverburden measured by Caregiverburden Scale | Caregiverburden in partners | 3, 12 and 24 months |
|
Heart Failure, Heart Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control<br>The dyads in the control group received care as usual including traditional care in hospital and outpatient education and support. The care is mainly focused on the patient's needs. The partner is not systematically involved in the follow-up focusing on education and psychosocial support. | |
| Experimental: Psycho edcuactional support<br>The intervention psychoeducational support to the patient-partner dyads was delivered in 3 sessions through nurse-led face-to-face counseling, a computer-based CD-ROM program and other written teaching materials. All sessions lasted at least 60 minutes and were conducted in the dyads' homes or in the heart failure clinic. The first session 2 weeks after discharge and the two remaining sessions 6- and 12-weeks following discharge. Each session included education on heart failure and development of problem- solving skills to assist the dyads in recognizing and modifying factors that contribute to psychological and emotional distress. The intervention focused on changing thoughts and behaviors and implementing strategies for self-care. | Behavioral: Psychoeducational support<br>* The intervention was based on a conceptual model from Stuifbergen. The model has sprung from Pender's model of health promotion and Bandura's self-efficacy theory. Cognitive-behavioral strategies were chosen to assist dyads in recognizing and modifying factors that contribute to physical and emotional distress by changing thoughts and behaviors and assisting dyads in solving problems related to implementing strategies for self-care.~Shared care is a dyadic process based on the assumption that each participant affects and is affected by the other. Shared goals and a shared commitment provide the essential building blocks of the dyad relationship. The dyad structure presents an opportunity for healthcare professionals to integrate a collaborative patient-partner centered effort.<br>|
|
Supporting Dyads Affected by Heart Failure
Study Overview
=================
Brief Summary
-----------------
The aim of this randomized controlled trial was to evaluate the effects of an integrated dyad care program with education and psychosocial support to patients with chronic heart failure and their partners during a post-discharge period after acute deterioration of heart failure. Methods: One hundred fifty five patient-caregiver dyads has been randomized to usual care or a psycho-education intervention delivered in three modules through nurse-led face-to-face counseling, computer-based education and other written teaching materials to assist dyads develop problem-solving skills. Follow-up assessments has been completed after 3, 12 and 24 months to assess perceived control, perceived health, depressive symptoms, self-care, knowledge, caregiver burden and health care utilization.
Detailed Description
-----------------
Heart failure is a serious condition with a poor prognosis. It is the leading cause of hospitalization and readmissions for worsening heart failure remains high. Treatment aims to reduce symptoms and morbidity and to improve quality of life and survival. Counseling and education is an important part of treatment, but despite the fact that most patients receive education, many are not able to adequately engage in self-care activities. Non-adherence to self-care recommendations is high which may be a contributing factor for worsening heart failure and to the high number of readmissions. Having support of a partner is important for patients with heart failure. Supportive others have the potential to improve self-care outcomes and increase adherence to treatment. At the same time, it should be acknowledged that the disease can also affect the partners negatively. However, emotional reactions of burden and stress decrease when partner's experiences control over the heart disease. Despite the fact that heart failure has a number of negative consequences for patients and the partners, research addressing self-care barriers from a family perspective is rare, and until now contemporary care has remained patient focused. Previous studies have indicated the importance of partner support but have not found the appropriate methods for involving and encourage partners. Therefore, studies focusing on the heart failure patient-partner dyad are needed, but to date, most studies have only evaluated short term effects of intervention programs, while long term effects might be of equally importance. The aim of this randomized controlled study was to evaluate the effects of an integrated dyad care program with education and psychosocial support to patients with chronic heart failure and their partners during a post-discharge period after acute deterioration of heart failure. Methods: One hundred fifty five patient-caregiver dyads has been randomized to usual care (n = 71) or a psycho-education intervention (n = 84) delivered in three modules through nurse-led face-to-face counseling, computer-based education and other written teaching materials to assist dyads develop problem-solving skills. Follow-up assessments has been completed after 3, 12 and 24 months to assess perceived control, perceived health, depressive symptoms, self-care, knowledge, caregiver burden and health care utilization.
Official Title
-----------------
Supporting Dyads Affected by Heart Failure - A Randomised Controlled Study Evaluating a Psychoeducational Intervention
Conditions
-----------------
Heart Failure
Intervention / Treatment
-----------------
* Behavioral: Psychoeducational support
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The inclusion criteria were to be a dyad consisting of a patient diagnosed with heart failure based on the European Society of Cardiology guidelines, New York Heart Association (NYHA) class II-IV, with a partner living in the same household as the patient, recently discharged from hospital (i.e. 2-3 weeks) following a heart failure acute exacerbation. Exclusion Criteria: Exclusion criteria for the dyads were dementia, or other severe psychiatric illnesses, drug abuse, difficulties in understanding or reading the Swedish language, undergoing cardiac surgery including cardiac transplant or participating in other studies.
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control<br>The dyads in the control group received care as usual including traditional care in hospital and outpatient education and support. The care is mainly focused on the patient's needs. The partner is not systematically involved in the follow-up focusing on education and psychosocial support. | |
| Experimental: Psycho edcuactional support<br>The intervention psychoeducational support to the patient-partner dyads was delivered in 3 sessions through nurse-led face-to-face counseling, a computer-based CD-ROM program and other written teaching materials. All sessions lasted at least 60 minutes and were conducted in the dyads' homes or in the heart failure clinic. The first session 2 weeks after discharge and the two remaining sessions 6- and 12-weeks following discharge. Each session included education on heart failure and development of problem- solving skills to assist the dyads in recognizing and modifying factors that contribute to psychological and emotional distress. The intervention focused on changing thoughts and behaviors and implementing strategies for self-care. | Behavioral: Psychoeducational support<br>* The intervention was based on a conceptual model from Stuifbergen. The model has sprung from Pender's model of health promotion and Bandura's self-efficacy theory. Cognitive-behavioral strategies were chosen to assist dyads in recognizing and modifying factors that contribute to physical and emotional distress by changing thoughts and behaviors and assisting dyads in solving problems related to implementing strategies for self-care. Shared care is a dyadic process based on the assumption that each participant affects and is affected by the other. Shared goals and a shared commitment provide the essential building blocks of the dyad relationship. The dyad structure presents an opportunity for healthcare professionals to integrate a collaborative patient-partner centered effort.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perceived control measure by Control Attitude Scale | Perceived control in patients and partners | 3 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life measure by SF-36 | Quality of life in patients and partners | 3, 12 and 24 months |
| Self care measured by European Self-care Behaviour Scale | Self care in patients | 3, 12 and 24 months |
| Caregiverburden measured by Caregiverburden Scale | Caregiverburden in partners | 3, 12 and 24 months |
|
|
NCT02874235
|
Music Therapy and Treatment as Usual
|
This study compares music therapy with verbal psychotherapy (treatment as usual) in an outpatient psychiatric clinic for traumatized refugees. Based on positive results from a pilot study, the randomized clinical trial has a non-inferiority design to detect whether music therapy is not less effective than verbal therapy carried out by psychologists and can serve as a complementary treatment modality (n=70).~The participants are adult Arabic, English or Danish speaking refugees suffering from posttraumatic stress disorder (PTSD). The patients are referred to outpatient treatment by their medical doctor. Data collection takes place in three locations of the clinic in Region Zealand, Denmark. The music therapy method used is Guided Imagery and Music (GIM).~Primary outcome is pre, post and 6 months follow-up measures of HTQ (Harvard Trauma Questionaire) and two measures of PTSD-8 during treatment. Secondary outcomes are pre, post and 6 months follow-up measures of Quality of Life Questionnaire (WHO-5), Dissociation Symptom Scale (DSS), Somatoform Dissociation Questionaire (SDQ-20), Revised Adult Attachment Scale (RAAS) and physiological measures (salivary oxytocin, betaendorphin and Substance P).
|
Subjects are randomized to 16 sessions of trauma modified GIM or 16 sessions of verbal psychotherapy (standard treatment).~N (70) is based on a power calculation using HTQ measures from similar refugee studies, with an estimated effect size in the range 0.6-0.8.~Sampling All baseline measures are scored during interview with a therapist before randomization. The primary post and follow-up measures (HTQ-R) are scored during interviews conducted by external psychologists blinded to the treatment group. The secondary post and follow-up measures are self-report questionnaires scored by the patients with the help of an educated translator who is blinded with regards to the treatment group.~0.5 ml salivary samples are collected in plastic tubes and stored at -20 degrees C.~The concentration of tree hormones (oxytocin, betaendorphin, substance P) are analyzed in a multiplex solution.~Intervention~The intervention is a phased trauma-oriented modification (tmGIM) of the Bonny Method of Guided Imagery and Music (GIM), where music listening and spontaneous imagery in an altered state of consciousness is used within a psychotherapeutic session to promote inner transformation and growth. The method was adapted by certain constraints:~Using only a limited selection of music with musical parameters, that fully support the trauma-oriented therapeutic goals and do not provoke flashbacks.~Using short music listening periods (2-10 minutes). Listening in an upright position. Inclusion of music from Middle-Eastern cultures. Inclusion of psychoeducation and introductory mindfulness based exercises such as mindful breathing and body awareness. Initial focus on inner resources such as positive memories, imagining a safe place and the use of the music breathing technics.
|
Music Therapy Versus Treatment as Usual: A Randomized Non-inferiority Study With Traumatized Refugees Diagnosed With PTSD
|
Stress Disorders, Post-Traumatic
|
* Behavioral: Receptive music therapy
* Behavioral: Psychological treatment
|
Inclusion Criteria:~Diagnostic Statistical Manual of Mental Disorders (DSM-5): Posttraumatic Stress Disorder Reaction: 309.81~Refugee status: Inhabitant in Denmark~International Classification of Diseases (ICD-10): F43.1: PTSD or~International Classification of Diseases (ICD-10): F62.0 Enduring personality change after catastrophic experience~Referred from a general practitioner or other unit of psychiatry~Exclusion Criteria:~International Classification of Diseases (ICD-10): F20-29 Schizophrenia or schizophrenia like diagnoses~Active Substance Abuse~Major Depression in connection with psychoses or suicidal risk
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HTQ-R | DSM IV PTSD symptoms part (first 16 items) of section 4 of HTQ. the Harvard Trauma Questionnaire is a 4 point Likert scale. Scored during an interview with an external psychologist blinded to the treatment group. Measured at baseline, post-treatment and at 6 months follow up. | 6 months |
| Change in PTSD-8 | DSM IV PTSD symptoms (8 of the first 16 items) of section 4 of HTQ. The Harvard Trauma Questionnaire is a Likert 4 point scale. PTSD is scored by the patient two times during treatment before session 4 and 12. This measure is also a part of the HTQ-R (Outcome 1) | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in WHO-5 | WHO-5 Quality of Life Scale, self-report questionnaire. Measured at baseline, post-treatment and at 6 months follow up. | 6 months |
| Change in RAAS | Revised Adult Attachment Scale. Attachment in close relationship self-report questionnaire. Measured at baseline, post-treatment and at 6 months follow up. | 6 months |
| Change in DSS | Dissociation Symptom Scale, self-report questionnaire. Measured at baseline, post-treatment and at 6 months follow up. | 6 months |
| Change in SDQ-20 | Somatoform Dissociation Questionnaire, self-report questionnaire. Measured at baseline, post-treatment and at 6 months follow up. | 6 months |
| Change in Oxytocin | Oxytocin collected in saliva. Measured at baseline, post-treatment and at 6 months follow up and. pre- and post session in the third or fourth session and second or third last session. | 6 months |
| Change in Beta-endorphin | Beta-endorphin collected in saliva. Measured at baseline, post-treatment and at 6 months follow up and pre- and post session in the third or fourth session and second or third last session. | 6 months |
| Change in Substance P | Substance P collected in saliva. Measured at baseline, post-treatment and at 6 months follow up and pre- and post session in the third or fourth session and second or third last session. | 6 months |
|
Stress Disorders, Post-Traumatic, Stress Disorders, Traumatic, Trauma and Stressor Related Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Music therapy treatment<br>35 patients receiving each 16 sessions of Receptive music therapy | Behavioral: Receptive music therapy<br>* 16 sessions of a length of one hour comprising of receptive music psychotherapy with 5 - 15 minutes of music listening included<br>* Other names: Modified Guided Imagery and Music;|
| Active Comparator: Standard treatment<br>35 patients receiving each 16 sessions of Psychological treatment | Behavioral: Psychological treatment<br>* 16 sessions of a length of one hour comprising of verbal based psychotherapy based on principles from Narrative Exposure Therapy or Cognitive Behavioral Therapies<br>|
|
Music Therapy and Treatment as Usual
Study Overview
=================
Brief Summary
-----------------
This study compares music therapy with verbal psychotherapy (treatment as usual) in an outpatient psychiatric clinic for traumatized refugees. Based on positive results from a pilot study, the randomized clinical trial has a non-inferiority design to detect whether music therapy is not less effective than verbal therapy carried out by psychologists and can serve as a complementary treatment modality (n=70). The participants are adult Arabic, English or Danish speaking refugees suffering from posttraumatic stress disorder (PTSD). The patients are referred to outpatient treatment by their medical doctor. Data collection takes place in three locations of the clinic in Region Zealand, Denmark. The music therapy method used is Guided Imagery and Music (GIM). Primary outcome is pre, post and 6 months follow-up measures of HTQ (Harvard Trauma Questionaire) and two measures of PTSD-8 during treatment. Secondary outcomes are pre, post and 6 months follow-up measures of Quality of Life Questionnaire (WHO-5), Dissociation Symptom Scale (DSS), Somatoform Dissociation Questionaire (SDQ-20), Revised Adult Attachment Scale (RAAS) and physiological measures (salivary oxytocin, betaendorphin and Substance P).
Detailed Description
-----------------
Subjects are randomized to 16 sessions of trauma modified GIM or 16 sessions of verbal psychotherapy (standard treatment). N (70) is based on a power calculation using HTQ measures from similar refugee studies, with an estimated effect size in the range 0.6-0.8. Sampling All baseline measures are scored during interview with a therapist before randomization. The primary post and follow-up measures (HTQ-R) are scored during interviews conducted by external psychologists blinded to the treatment group. The secondary post and follow-up measures are self-report questionnaires scored by the patients with the help of an educated translator who is blinded with regards to the treatment group. 0.5 ml salivary samples are collected in plastic tubes and stored at -20 degrees C. The concentration of tree hormones (oxytocin, betaendorphin, substance P) are analyzed in a multiplex solution. Intervention The intervention is a phased trauma-oriented modification (tmGIM) of the Bonny Method of Guided Imagery and Music (GIM), where music listening and spontaneous imagery in an altered state of consciousness is used within a psychotherapeutic session to promote inner transformation and growth. The method was adapted by certain constraints: Using only a limited selection of music with musical parameters, that fully support the trauma-oriented therapeutic goals and do not provoke flashbacks. Using short music listening periods (2-10 minutes). Listening in an upright position. Inclusion of music from Middle-Eastern cultures. Inclusion of psychoeducation and introductory mindfulness based exercises such as mindful breathing and body awareness. Initial focus on inner resources such as positive memories, imagining a safe place and the use of the music breathing technics.
Official Title
-----------------
Music Therapy Versus Treatment as Usual: A Randomized Non-inferiority Study With Traumatized Refugees Diagnosed With PTSD
Conditions
-----------------
Stress Disorders, Post-Traumatic
Intervention / Treatment
-----------------
* Behavioral: Receptive music therapy
* Behavioral: Psychological treatment
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnostic Statistical Manual of Mental Disorders (DSM-5): Posttraumatic Stress Disorder Reaction: 309.81 Refugee status: Inhabitant in Denmark International Classification of Diseases (ICD-10): F43.1: PTSD or International Classification of Diseases (ICD-10): F62.0 Enduring personality change after catastrophic experience Referred from a general practitioner or other unit of psychiatry Exclusion Criteria: International Classification of Diseases (ICD-10): F20-29 Schizophrenia or schizophrenia like diagnoses Active Substance Abuse Major Depression in connection with psychoses or suicidal risk
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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Music therapy treatment<br>35 patients receiving each 16 sessions of Receptive music therapy | Behavioral: Receptive music therapy<br>* 16 sessions of a length of one hour comprising of receptive music psychotherapy with 5 - 15 minutes of music listening included<br>* Other names: Modified Guided Imagery and Music;|
| Active Comparator: Standard treatment<br>35 patients receiving each 16 sessions of Psychological treatment | Behavioral: Psychological treatment<br>* 16 sessions of a length of one hour comprising of verbal based psychotherapy based on principles from Narrative Exposure Therapy or Cognitive Behavioral Therapies<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HTQ-R | DSM IV PTSD symptoms part (first 16 items) of section 4 of HTQ. the Harvard Trauma Questionnaire is a 4 point Likert scale. Scored during an interview with an external psychologist blinded to the treatment group. Measured at baseline, post-treatment and at 6 months follow up. | 6 months |
| Change in PTSD-8 | DSM IV PTSD symptoms (8 of the first 16 items) of section 4 of HTQ. The Harvard Trauma Questionnaire is a Likert 4 point scale. PTSD is scored by the patient two times during treatment before session 4 and 12. This measure is also a part of the HTQ-R (Outcome 1) | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in WHO-5 | WHO-5 Quality of Life Scale, self-report questionnaire. Measured at baseline, post-treatment and at 6 months follow up. | 6 months |
| Change in RAAS | Revised Adult Attachment Scale. Attachment in close relationship self-report questionnaire. Measured at baseline, post-treatment and at 6 months follow up. | 6 months |
| Change in DSS | Dissociation Symptom Scale, self-report questionnaire. Measured at baseline, post-treatment and at 6 months follow up. | 6 months |
| Change in SDQ-20 | Somatoform Dissociation Questionnaire, self-report questionnaire. Measured at baseline, post-treatment and at 6 months follow up. | 6 months |
| Change in Oxytocin | Oxytocin collected in saliva. Measured at baseline, post-treatment and at 6 months follow up and. pre- and post session in the third or fourth session and second or third last session. | 6 months |
| Change in Beta-endorphin | Beta-endorphin collected in saliva. Measured at baseline, post-treatment and at 6 months follow up and pre- and post session in the third or fourth session and second or third last session. | 6 months |
| Change in Substance P | Substance P collected in saliva. Measured at baseline, post-treatment and at 6 months follow up and pre- and post session in the third or fourth session and second or third last session. | 6 months |
|
|
NCT02400554
|
Yappalli - The Road to Choctaw Health
|
This is an obesity and alcohol, tobacco, and other drug (ATOD) use risk prevention and health leadership program. This project will include 150 at-risk adult Native women across 5 communities (30 women from each community) in the Choctaw Nation of Oklahoma. The intervention targets individual behavioral change relative to ATOD and obesity prevention and simultaneously provides behavioral skills for health promotion leadership.~Investigators will conduct a longitudinal study using a cluster randomized stepped-wedge design to evaluate the intervention impact on ATOD and obesity prevention primary aims of: (1) substance use harm reduction and ATOD use and intentions to use; and (2) reduction in weight/body mass index (BMI) and increase in leisure-time physical activity/physical activity (LTPA/PA) and healthful food habits. Specifically, investigators will ask participants to participate in up to eight group sessions (based on a curriculum drawing on cultural teachings around health and behavioral change); attend up to three Motivational Interviewing individual sessions (to identify individual behavioral change goals); attend a two-day overnight culture and Trail prep camp; participate in camping and walking for up to 10 days on the Trail; and attend up to six post-walk meetings (to develop community health events). All five communities will also be asked to complete a baseline health assessment as well as three follow up assessments over the course of the year. Additionally, communities 2-5 will participate in three pre-intervention health assessments. This intervention integrates components of motivational interviewing, information-motivation-behavior, and a leadership development framework for adults. It targets individual behavioral change relative to ATOD and obesity prevention and simultaneously provides behavioral skills for health promotion leadership within their respective communities.The project addresses a critical public health issue among a group experiencing considerable health disparities and strengthens the research infrastructure in partnership with the Tribe. If efficacious, it has the potential for widespread dissemination and could be generalizable to other chronic co-occurring mental health and physical health conditions.
|
Study Design:~Investigators will conduct a 5-community longitudinal study using a cluster randomized stepped-wedge design to evaluate the intervention impact on alcohol, tobacco, and other drug (ATOD) and obesity prevention primary aims of: (1) substance use harm reduction, overall ATOD use and intentions to use; and (2) weight/body mass index (BMI) change as well as the effect on leisure-time physical activity/physical activity (LTPA/PA), and healthful food habits among adult Choctaw women at risk for obesity and ATOD. The cluster randomized stepped-wedge design is a type of cross-over study in which clusters of women from each community cross over to the intervention arm at randomly assigned time points (one time per year, per community).~Sequence and Timing of Study Procedures:~Randomization: Investigators have created five regional communities and within each community a convenience sample will be drawn. Each site has been randomly assigned to start the intervention at a given year. Randomization occurs only to determine the year each community enters the study. Community 1 will begin the intervention immediately; communities 2-5 will complete three health assessments prior to beginning the intervention. These will occur at the same time of post-walk assessments for the community currently in the intervention (i.e. community 2 does health assessments in the same months community 1 does post-walk assessments and then begins the intervention in Year 2.)~Recruitment and Screening of Participants:~Recruitment strategies:~Referrals from staff from Choctaw Nation of Oklahoma (CNO) project staff, staff at Choctaw Nation Health Services Authority (CNHSA), Community Advisory Council members, health providers, and general community members. They will provide potential participants with a flyer and encourage women to call if interested.~The following strategies will be used as necessary: posting flyers in community health clinics, stores, community centers, and other locations identified by our community advisors; and posting flyers in the tribal newspaper, other local news outlets, and on a study Facebook page.~Recruitment materials will invite American Indian/Alaska Native women who are interested in participating in the research study to call a dedicated, toll-free phone number or the project number at Choctaw Nation.~Screening:~Participants can opt for a phone or in-person screen using the same script.~CNO study staff will answer and return phone calls and conduct the screens. Indigenous Wellness Research Institute (IWRI) staff will conduct eligibility screens on the phone as needed.~Women screened out will be given a community resource list. Phone screeners will offer to mail or email the list.~If a person is eligible, but declines to participate, they will be given a brief one-item exit question regarding general reason for non-participation.~Eligible women who agree to participate will be asked to schedule their baseline assessment.~Participants will receive reminders by email, text or phone 2 days before, the day before, and the day of any meetings, assessments, or events.~Consent and Baseline Assessment:~The baseline assessment consists of a brief physical health assessment and a computer-assisted behavioral health survey administered by study staff. The physical health assessment is a non-invasive procedure that involves the measurement of BMI (with portable digital weight scale and height measure) and blood pressure. The computer-assisted behavioral health survey will ask a series of questions and take under 90 minutes to complete.~After consent is obtained, CNO study staff will set up the study laptop and headphones that the participant will use to enter their responses to the questionnaire. The variable matrix includes instructions, prompts, response scales, and references for all measures used for each behavioral health assessment.~Group Sessions/Yappalli Curriculum (Months 1-3) Participants will attend up to eight group sessions. The curriculum for these sessions includes: learning about Choctaw history, traditions,and cultural systems as well as women's roles (e.g., Treaty of Dancing Rabbit Creek); participating in cultural activities (e.g., stickball or social dances); developing traditionally-based materials (e.g., walking sticks); and using cultural metaphors for behavioral changes (e.g., 4 pillars of wellness-mind, body, spirit, emotion)). Experiential, outdoor activities are incorporated to promote group cohesion, improve relational worldviews, and connectedness to nature and the environment. Examples include activities on an outdoor ropes course maintained and managed by CNHSA or increasing LTPA/PA by walking or gardening.~Motivational Interviewing Individual Sessions (Months 1-3) In up to three sessions, participants will identify personal change goals on the main outcome variables as well as community leadership goals. These sessions will target four areas: increasing physical activity or movement; reducing or eliminating junk snack foods, sweets, and sugared soft drinks; decreasing addiction and or potential to misuse tobacco, alcohol or other substances and food; and increasing community leadership skills.~Culture Camp (Month 2) In this two-day, overnight camp participants will practice camping and being outdoors (e.g., setting up tents, trying out new shoes and equipment, etc.) and begin to strengthen group cohesion prior to embarking on the Trail. It is also designed to synthesize goals and cultural values discussed in the group and individual sessions.~Trail of Tears Walk (Month 3) Participants will gather at a location in Oklahoma before driving to a starting point at the Mississippi/Arkansas border then follow one of the routes of the Choctaw Trail of Tears through Arkansas and back into Oklahoma. They will walk on average 8-10 miles per day and travel by van for a portion of the trail to a different campsite each day. At the end of the trip, the walkers will have walked approximately 60-80 miles over the 260 mile route. On the last night of the Trail, participants will make a vow to conduct a community-wide event (based on personal and leadership goals and experience on the Trail) within nine months. Note: a support van will travel along with walkers so that they could walk as many minutes or miles they feel comfortable doing (e.g., from 10 mins. Less than a quarter mile to 10 miles).~Post-Walk assessments (Months 3-12) Three follow-up health assessments will occur: one immediately post-walk in Month 3, one in Month 9, and one in Month 12. These behavioral health assessments will be collected in the same manner and include a similar set of measures as the baseline assessment. The physical health assessments will also be conducted in the same manner as the baseline assessment.~Post-Walk Group Meetings (Months 3-12) Participants will attend up to six group meetings to plan community leadership events (investigators provide a small budget for the women to create a community event such as a community food garden). Specific meetings include: at three months post-walk a digital storytelling training to create a story related to ATOD and obesity prevention and their personal experiences; and at six months post-walk an individual MI booster session to revise their personal vows/goals and community leadership goals.~Final Community Event (Month 12) Participants will share digital stories and/or community event experiences and undergo a naming ceremony as they transition to health leaders within their communities. They will be given the option to become a member of one of seven Choctaw health promotion societies on which the intervention is based to continue their health promotion leadership efforts after their participation in the project ends.
|
Yappalli - The Road to Choctaw Health
|
Obesity, Substance Abuse
|
* Behavioral: Yappalli
|
Inclusion Criteria:~Self-identify as women~Be enrolled in the Choctaw Nation of Oklahoma~Reside in the designated county~Be 18 years of age or older~Have tried any tobacco, alcohol, or drugs OR ever felt out of control with any food in past 5 years~Be able to walk unassisted for at least 10 minutes~Exclusion Criteria:~Women who are actively using opioids (i.e., heroin) methamphetamines and/or abusing prescription drugs not prescribed to them (e.g., Dilaudid, Oxycontin) or alcohol dependent (5+ bottles/glasses of alcohol a day).~Women who exhibit serious psychiatric symptoms determined by CNO trained staff.~Women who have been suicidal in past 3 months, are currently pregnant, or are denied medical approval.
|
18 Years
| null |
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Food Habits as assessed by the Yale Food Addiction Scale | Yale Food Addiction Scale - continuous measure items | Post-Walk (month 3) and Post Intervention (month 12) |
| Weight Change | Investigators will assess weight change for each individual | Post-Walk (month 3) and Post Intervention (month 12) |
| Changes in Physical Activity assessed using items from the California Health Interview Survey | Investigators will assess changes in physical activity and leisure time activity in participants using items from the California Health Interview Survey | Post-Walk (month 3) and Post Intervention (month 12) |
| Change in Alcohol Use as assessed by the Alcohol Use Disorders Identification Test. | Assess changes in alcohol use (frequency, amount, consequences and context) using the Alcohol Use Disorders Identification Test. | Post-Walk (month 3) and Post Intervention (month 12) |
| Change in Other Substance Use as assessed by the Phen-X toolkit | Phen-X toolkit for 30-Day Use (for items that are applicable) | Post-Walk (month 3) and Post Intervention (month 12) |
|
Indian, North American, Oklahoma, Female, health promotion
|
Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Wait List Control<br>Participants wait one year before receiving the intervention. Three assessments are taken over this period: Month 3, Month 9, and Month 12. | |
| Experimental: Yappalli<br>Yappalli: Participants attend a 12-month behavioral intervention. | Behavioral: Yappalli<br>* Month 1-3: Up to 8 group sessions on Choctaw history, traditions, cultural systems, & women's roles. Up to 3 individual Motivational Interviewing (MI) sessions to identify community leadership & personal change goals on the main outcome.~Month 2: Overnight Culture Camp to strengthen group cohesion & synthesize goals.~Month 3: Walk for a week on the Choctaw Trail of Tears, upon completion make a commitment to conduct a community-wide event based on personal & leadership goals & experience on the Trail.~Months 3-12: Up to 6 group meetings to plan community leadership events related to ATOD & obesity prevention. Includes: digital storytelling training to create a story related to ATOD & obesity prevention & an individual MI booster session to revise their personal & community leadership goals.~Month 12: Share digital stories & community event experiences & undergo a ceremony to transition to health leaders within their communities.<br>|
|
Yappalli - The Road to Choctaw Health
Study Overview
=================
Brief Summary
-----------------
This is an obesity and alcohol, tobacco, and other drug (ATOD) use risk prevention and health leadership program. This project will include 150 at-risk adult Native women across 5 communities (30 women from each community) in the Choctaw Nation of Oklahoma. The intervention targets individual behavioral change relative to ATOD and obesity prevention and simultaneously provides behavioral skills for health promotion leadership. Investigators will conduct a longitudinal study using a cluster randomized stepped-wedge design to evaluate the intervention impact on ATOD and obesity prevention primary aims of: (1) substance use harm reduction and ATOD use and intentions to use; and (2) reduction in weight/body mass index (BMI) and increase in leisure-time physical activity/physical activity (LTPA/PA) and healthful food habits. Specifically, investigators will ask participants to participate in up to eight group sessions (based on a curriculum drawing on cultural teachings around health and behavioral change); attend up to three Motivational Interviewing individual sessions (to identify individual behavioral change goals); attend a two-day overnight culture and Trail prep camp; participate in camping and walking for up to 10 days on the Trail; and attend up to six post-walk meetings (to develop community health events). All five communities will also be asked to complete a baseline health assessment as well as three follow up assessments over the course of the year. Additionally, communities 2-5 will participate in three pre-intervention health assessments. This intervention integrates components of motivational interviewing, information-motivation-behavior, and a leadership development framework for adults. It targets individual behavioral change relative to ATOD and obesity prevention and simultaneously provides behavioral skills for health promotion leadership within their respective communities.The project addresses a critical public health issue among a group experiencing considerable health disparities and strengthens the research infrastructure in partnership with the Tribe. If efficacious, it has the potential for widespread dissemination and could be generalizable to other chronic co-occurring mental health and physical health conditions.
Detailed Description
-----------------
Study Design: Investigators will conduct a 5-community longitudinal study using a cluster randomized stepped-wedge design to evaluate the intervention impact on alcohol, tobacco, and other drug (ATOD) and obesity prevention primary aims of: (1) substance use harm reduction, overall ATOD use and intentions to use; and (2) weight/body mass index (BMI) change as well as the effect on leisure-time physical activity/physical activity (LTPA/PA), and healthful food habits among adult Choctaw women at risk for obesity and ATOD. The cluster randomized stepped-wedge design is a type of cross-over study in which clusters of women from each community cross over to the intervention arm at randomly assigned time points (one time per year, per community). Sequence and Timing of Study Procedures: Randomization: Investigators have created five regional communities and within each community a convenience sample will be drawn. Each site has been randomly assigned to start the intervention at a given year. Randomization occurs only to determine the year each community enters the study. Community 1 will begin the intervention immediately; communities 2-5 will complete three health assessments prior to beginning the intervention. These will occur at the same time of post-walk assessments for the community currently in the intervention (i.e. community 2 does health assessments in the same months community 1 does post-walk assessments and then begins the intervention in Year 2.) Recruitment and Screening of Participants: Recruitment strategies: Referrals from staff from Choctaw Nation of Oklahoma (CNO) project staff, staff at Choctaw Nation Health Services Authority (CNHSA), Community Advisory Council members, health providers, and general community members. They will provide potential participants with a flyer and encourage women to call if interested. The following strategies will be used as necessary: posting flyers in community health clinics, stores, community centers, and other locations identified by our community advisors; and posting flyers in the tribal newspaper, other local news outlets, and on a study Facebook page. Recruitment materials will invite American Indian/Alaska Native women who are interested in participating in the research study to call a dedicated, toll-free phone number or the project number at Choctaw Nation. Screening: Participants can opt for a phone or in-person screen using the same script. CNO study staff will answer and return phone calls and conduct the screens. Indigenous Wellness Research Institute (IWRI) staff will conduct eligibility screens on the phone as needed. Women screened out will be given a community resource list. Phone screeners will offer to mail or email the list. If a person is eligible, but declines to participate, they will be given a brief one-item exit question regarding general reason for non-participation. Eligible women who agree to participate will be asked to schedule their baseline assessment. Participants will receive reminders by email, text or phone 2 days before, the day before, and the day of any meetings, assessments, or events. Consent and Baseline Assessment: The baseline assessment consists of a brief physical health assessment and a computer-assisted behavioral health survey administered by study staff. The physical health assessment is a non-invasive procedure that involves the measurement of BMI (with portable digital weight scale and height measure) and blood pressure. The computer-assisted behavioral health survey will ask a series of questions and take under 90 minutes to complete. After consent is obtained, CNO study staff will set up the study laptop and headphones that the participant will use to enter their responses to the questionnaire. The variable matrix includes instructions, prompts, response scales, and references for all measures used for each behavioral health assessment. Group Sessions/Yappalli Curriculum (Months 1-3) Participants will attend up to eight group sessions. The curriculum for these sessions includes: learning about Choctaw history, traditions,and cultural systems as well as women's roles (e.g., Treaty of Dancing Rabbit Creek); participating in cultural activities (e.g., stickball or social dances); developing traditionally-based materials (e.g., walking sticks); and using cultural metaphors for behavioral changes (e.g., 4 pillars of wellness-mind, body, spirit, emotion)). Experiential, outdoor activities are incorporated to promote group cohesion, improve relational worldviews, and connectedness to nature and the environment. Examples include activities on an outdoor ropes course maintained and managed by CNHSA or increasing LTPA/PA by walking or gardening. Motivational Interviewing Individual Sessions (Months 1-3) In up to three sessions, participants will identify personal change goals on the main outcome variables as well as community leadership goals. These sessions will target four areas: increasing physical activity or movement; reducing or eliminating junk snack foods, sweets, and sugared soft drinks; decreasing addiction and or potential to misuse tobacco, alcohol or other substances and food; and increasing community leadership skills. Culture Camp (Month 2) In this two-day, overnight camp participants will practice camping and being outdoors (e.g., setting up tents, trying out new shoes and equipment, etc.) and begin to strengthen group cohesion prior to embarking on the Trail. It is also designed to synthesize goals and cultural values discussed in the group and individual sessions. Trail of Tears Walk (Month 3) Participants will gather at a location in Oklahoma before driving to a starting point at the Mississippi/Arkansas border then follow one of the routes of the Choctaw Trail of Tears through Arkansas and back into Oklahoma. They will walk on average 8-10 miles per day and travel by van for a portion of the trail to a different campsite each day. At the end of the trip, the walkers will have walked approximately 60-80 miles over the 260 mile route. On the last night of the Trail, participants will make a vow to conduct a community-wide event (based on personal and leadership goals and experience on the Trail) within nine months. Note: a support van will travel along with walkers so that they could walk as many minutes or miles they feel comfortable doing (e.g., from 10 mins. Less than a quarter mile to 10 miles). Post-Walk assessments (Months 3-12) Three follow-up health assessments will occur: one immediately post-walk in Month 3, one in Month 9, and one in Month 12. These behavioral health assessments will be collected in the same manner and include a similar set of measures as the baseline assessment. The physical health assessments will also be conducted in the same manner as the baseline assessment. Post-Walk Group Meetings (Months 3-12) Participants will attend up to six group meetings to plan community leadership events (investigators provide a small budget for the women to create a community event such as a community food garden). Specific meetings include: at three months post-walk a digital storytelling training to create a story related to ATOD and obesity prevention and their personal experiences; and at six months post-walk an individual MI booster session to revise their personal vows/goals and community leadership goals. Final Community Event (Month 12) Participants will share digital stories and/or community event experiences and undergo a naming ceremony as they transition to health leaders within their communities. They will be given the option to become a member of one of seven Choctaw health promotion societies on which the intervention is based to continue their health promotion leadership efforts after their participation in the project ends.
Official Title
-----------------
Yappalli - The Road to Choctaw Health
Conditions
-----------------
Obesity, Substance Abuse
Intervention / Treatment
-----------------
* Behavioral: Yappalli
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Self-identify as women Be enrolled in the Choctaw Nation of Oklahoma Reside in the designated county Be 18 years of age or older Have tried any tobacco, alcohol, or drugs OR ever felt out of control with any food in past 5 years Be able to walk unassisted for at least 10 minutes Exclusion Criteria: Women who are actively using opioids (i.e., heroin) methamphetamines and/or abusing prescription drugs not prescribed to them (e.g., Dilaudid, Oxycontin) or alcohol dependent (5+ bottles/glasses of alcohol a day). Women who exhibit serious psychiatric symptoms determined by CNO trained staff. Women who have been suicidal in past 3 months, are currently pregnant, or are denied medical approval.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Sexes Eligible for Study
-----------------
Female
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 |
| --- | --- |
| No Intervention: Wait List Control<br>Participants wait one year before receiving the intervention. Three assessments are taken over this period: Month 3, Month 9, and Month 12. | |
| Experimental: Yappalli<br>Yappalli: Participants attend a 12-month behavioral intervention. | Behavioral: Yappalli<br>* Month 1-3: Up to 8 group sessions on Choctaw history, traditions, cultural systems, & women's roles. Up to 3 individual Motivational Interviewing (MI) sessions to identify community leadership & personal change goals on the main outcome. Month 2: Overnight Culture Camp to strengthen group cohesion & synthesize goals. Month 3: Walk for a week on the Choctaw Trail of Tears, upon completion make a commitment to conduct a community-wide event based on personal & leadership goals & experience on the Trail. Months 3-12: Up to 6 group meetings to plan community leadership events related to ATOD & obesity prevention. Includes: digital storytelling training to create a story related to ATOD & obesity prevention & an individual MI booster session to revise their personal & community leadership goals. Month 12: Share digital stories & community event experiences & undergo a ceremony to transition to health leaders within their communities.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Food Habits as assessed by the Yale Food Addiction Scale | Yale Food Addiction Scale - continuous measure items | Post-Walk (month 3) and Post Intervention (month 12) |
| Weight Change | Investigators will assess weight change for each individual | Post-Walk (month 3) and Post Intervention (month 12) |
| Changes in Physical Activity assessed using items from the California Health Interview Survey | Investigators will assess changes in physical activity and leisure time activity in participants using items from the California Health Interview Survey | Post-Walk (month 3) and Post Intervention (month 12) |
| Change in Alcohol Use as assessed by the Alcohol Use Disorders Identification Test. | Assess changes in alcohol use (frequency, amount, consequences and context) using the Alcohol Use Disorders Identification Test. | Post-Walk (month 3) and Post Intervention (month 12) |
| Change in Other Substance Use as assessed by the Phen-X toolkit | Phen-X toolkit for 30-Day Use (for items that are applicable) | Post-Walk (month 3) and Post Intervention (month 12) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Indian, North American, Oklahoma, Female, health promotion
|
|
NCT00235027
|
Improving Safety By Computerizing Outpatient Prescribing
|
Patient safety is at the forefront of critical issues in health care. Medications are the single most frequent cause of adverse events, and in the inpatient setting adverse drug events (ADEs) are common, expensive, injurious to patients, and often preventable. Relatively little, however, is known about the frequency of ADEs in the ambulatory setting, how to monitor for outpatient ADEs, or on the impact of prevention strategies such as computerization of prescribing supplemented by decision-support.
|
Specific Aim 1: Increase routine identification of outpatient adverse drug events (ADEs) through development of a computerized ADE detection monitor.~Specific Aim 2: Use basic computerized outpatient prescribing to reduce preventable ADEs in a diverse array of outpatient settings.~Specific Aim 3: Use advanced decision-support within computerized prescribing to reduce the frequency of preventable ADEs, medication errors, and potential ADEs.
|
Improving Safety By Computerizing Outpatient Prescribing
|
Impact of Electronic Prescribing on Medication Safety
|
* Other: Adverse Drug Event Monitoring
|
Inclusion Criteria: At Brigham & Women's Hospital, clinics utilizing the electronic medical record will be included. At Regenstrief, any clinic that has access to their electronic medical record will be utilized.~For the impact of basic decision support, clinics were not randomized~For impact of advanced decision support, clinics were randomized to receive the intervention~Exclusion Criteria:~Clinics not using electronic medical records
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preventable Adverse drug events | Data were electronically collected each time a physician entered a prescription that triggered an alert related to medication safety. | 8/5/2004 - 1/5/2005 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total adverse drug events, medication errors | | 1/15/2001 - 5/15/2001 |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adverse Drug Event Monitoring<br>In this intervention arm, clinicians received medication safety alerts when they prescribed medications in the electronic medical record. | Other: Adverse Drug Event Monitoring<br>* The intervention in this study is the presentation of medication safety alerts in the electronic medical record to improve patient outcomes and safety.<br>|
| No Intervention: Care as Usual<br>In this arm, clinicians did not receive the medication safety alerts. | |
|
Improving Safety By Computerizing Outpatient Prescribing
Study Overview
=================
Brief Summary
-----------------
Patient safety is at the forefront of critical issues in health care. Medications are the single most frequent cause of adverse events, and in the inpatient setting adverse drug events (ADEs) are common, expensive, injurious to patients, and often preventable. Relatively little, however, is known about the frequency of ADEs in the ambulatory setting, how to monitor for outpatient ADEs, or on the impact of prevention strategies such as computerization of prescribing supplemented by decision-support.
Detailed Description
-----------------
Specific Aim 1: Increase routine identification of outpatient adverse drug events (ADEs) through development of a computerized ADE detection monitor. Specific Aim 2: Use basic computerized outpatient prescribing to reduce preventable ADEs in a diverse array of outpatient settings. Specific Aim 3: Use advanced decision-support within computerized prescribing to reduce the frequency of preventable ADEs, medication errors, and potential ADEs.
Official Title
-----------------
Improving Safety By Computerizing Outpatient Prescribing
Conditions
-----------------
Impact of Electronic Prescribing on Medication Safety
Intervention / Treatment
-----------------
* Other: Adverse Drug Event Monitoring
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: At Brigham & Women's Hospital, clinics utilizing the electronic medical record will be included. At Regenstrief, any clinic that has access to their electronic medical record will be utilized. For the impact of basic decision support, clinics were not randomized For impact of advanced decision support, clinics were randomized to receive the intervention Exclusion Criteria: Clinics not using electronic medical records
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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adverse Drug Event Monitoring<br>In this intervention arm, clinicians received medication safety alerts when they prescribed medications in the electronic medical record. | Other: Adverse Drug Event Monitoring<br>* The intervention in this study is the presentation of medication safety alerts in the electronic medical record to improve patient outcomes and safety.<br>|
| No Intervention: Care as Usual<br>In this arm, clinicians did not receive the medication safety alerts. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preventable Adverse drug events | Data were electronically collected each time a physician entered a prescription that triggered an alert related to medication safety. | 8/5/2004 - 1/5/2005 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total adverse drug events, medication errors | | 1/15/2001 - 5/15/2001 |
|
||
NCT04296643
|
Medical Masks vs N95 Respirators for COVID-19
|
A randomized controlled trial in which health care workers will be randomized to either medical masks or N95 respirators when providing care to patients with COVID-19.
|
A randomized controlled trial in which health care workers will be randomized to either medical masks or N95 respirators when providing medical care to patients with COVID-19. This multi-centre randomized controlled trial will assess whether medical masks are non-inferior to N95 respirators when health care workers provide care involving non-aerosol generating procedures. Health care workers will be randomized to either use of a medical mask or to a fit-tested N95 respirator when providing care for patients with febrile respiratory illness. Health care workers randomly assigned to the N95 respirator group will be instructed to use a fit-tested National Institute for Occupational Safety and Health-approved N95 respirator when providing routine care to patients with COVID-19 or suspected COVID-19. Participants will use the type of device they were allocated to, either a medical mask or an N95 respirator, for 10 weeks, however, health care workers can also use the N95 respirator at any time based on a point-of-care risk assessment. Universal masking is the policy implemented at each study site. Extended and re-use of N95 respirators will be permitted if the local situation requires it. The primary outcome is laboratory confirmed RT-PCR COVID-19 among participants.~A nasopharyngeal swab will be obtained if any one of the following symptoms or signs is present: fever (≥38 C), cough, or shortness of breath, or if 2 of the following are present: fatigue, myalgia, headache, dizziness, expectoration, sore throat, diarrhea, nausea, vomiting, abdominal pain, runny nose, altered taste or smell, conjunctivitis, or painful swallowing.~Participants that receive a COVID-19 vaccine after enrollment with efficacy of > 50% for the circulating strain will continue to be followed until 2 weeks after the first dose of the vaccine. All other participants will be followed for 10 weeks.~Self-reporting of hand hygiene and the use of external monitors, where feasible, will be used to collect basic hand hygiene data.~The sample size is 1,010 participants. This will allow 90% power at an alpha (one sided) of 0.05 and to account for participants who may not have completed 10 weeks because of COVID-19 mRNA vaccination.~Changes made to the protocol prior to May 4, 2020, which was prior to the start of enrollment:~Eligibility criteria expanded from nurses who provide direct patient care to health care workers that provide direct patient care.~Allowed extended and re-use of N95 respirators if the local situation required it.~Added self-reporting of hand hygiene and the use of external monitors if feasible.~Reduced the duration of follow up from 12 weeks to 10 weeks~Changes made on or after May 4, 2020:~Expanded the criteria for the requirement of swabs to detect COVID-19 by adding runny nose, altered taste or smell, and conjunctivitis and also asked for a swab for fever, cough, or shortness of breath alone OR for two of the previously listed symptoms or signs (May 19, 2020).~Added previously known COVID infection as an exclusion (October, 30, 2020).~Added receipt of a COVID-19 vaccine with efficacy of > 50% as an exclusion (October 30, 2020).~Allowed those participants that received a COVID-19 vaccine after enrollment with efficacy of > 50% for the circulating strain to continue to be followed until 2 weeks after the first dose of the vaccine (December 17, 2020).~Increased the sample size to 1,010 participants to allow 90% power at an alpha (one sided) of 0.05 and to account for participants who may not have completed 10 weeks because of COVID-19 mRNA vaccination (July 26, 2021).~Added wording to capture implementation since May 4th, 2020, Where the policy of the healthcare setting has been universal use of a facemask, that is wearing a facemask at all times when in the hospital, then the facemask participants were randomized to will be used. (December 27, 2021)
|
Medical Masks Versus N95 Respirators to Prevent 2019 Novel Coronavirus Disease (COVID-19) in Healthcare Workers: A Randomized Trial
|
N95, Coronavirus, Medical Mask
|
* Device: Medical Mask
* Device: N95 respirator
|
Inclusion Criteria:~Health care workers who provide direct care to patients with suspected or confirmed COVID-19 in specialized COVID-19 units and in emergency departments, medical units, pediatric units, and long-term care facilities~Health care workers are required to spend 60% or more of their time doing clinical work when enrolled.~Exclusion Criteria:~Unable to pass or do not have a valid fit test within the past 24 months~One or more high-risk comorbidities for COVID-19 (hypertension, cardiac disease, pulmonary disease, chronic kidney disease, diabetes, chronic liver disease, actively treated cancer, or immunosuppression due to illness or medications)~Previous laboratory confirmed clinical diagnosis of COVID-19 at the time of~Received 1 or more doses of a COVID-19 vaccine with greater than 50% efficacy for the circulating strain (for example, mRNA or vector-based COVID-19 vaccine against the original SARS-CoV-2 strain).~working in intensive care units.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: pragmatic, randomized, open-label, multicentre, noninferiority trial.
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RT-PCR confirmed COVID-19 infection | Number of participants with RT-PCR confirmed COVID-19 infection | 10 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute respiratory illness | Number of participants with acute respiratory illness | 10 weeks |
| Absenteeism | Number of participants with absenteeism | 10 weeks |
| Lower respiratory infection | Number of participants with lower respiratory infection | 10 weeks |
| Pneumonia | Number of participants with pneumonia | 10 weeks |
| ICU admission | Number of participants with ICU admission | 10 weeks |
| Mechanical ventilation | Number of participants needing mechanical ventilation | 10 weeks |
| Death | Number of participants that died | 10 weeks |
|
Coronavirus Infections, Coronaviridae Infections, Nidovirales Infections, RNA Virus Infections, Virus Diseases, Infections
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medical Mask<br>Medical Mask worn when providing care to patient with febrile respiratory illness | Device: Medical Mask<br>* Medical Mask (known also as Surgical Mask)<br>|
| Active Comparator: N95 respirator<br>N95 respirator worn when providing care to patient with febrile respiratory illness | Device: N95 respirator<br>* N95 respirator<br>|
|
Medical Masks vs N95 Respirators for COVID-19
Study Overview
=================
Brief Summary
-----------------
A randomized controlled trial in which health care workers will be randomized to either medical masks or N95 respirators when providing care to patients with COVID-19.
Detailed Description
-----------------
A randomized controlled trial in which health care workers will be randomized to either medical masks or N95 respirators when providing medical care to patients with COVID-19. This multi-centre randomized controlled trial will assess whether medical masks are non-inferior to N95 respirators when health care workers provide care involving non-aerosol generating procedures. Health care workers will be randomized to either use of a medical mask or to a fit-tested N95 respirator when providing care for patients with febrile respiratory illness. Health care workers randomly assigned to the N95 respirator group will be instructed to use a fit-tested National Institute for Occupational Safety and Health-approved N95 respirator when providing routine care to patients with COVID-19 or suspected COVID-19. Participants will use the type of device they were allocated to, either a medical mask or an N95 respirator, for 10 weeks, however, health care workers can also use the N95 respirator at any time based on a point-of-care risk assessment. Universal masking is the policy implemented at each study site. Extended and re-use of N95 respirators will be permitted if the local situation requires it. The primary outcome is laboratory confirmed RT-PCR COVID-19 among participants. A nasopharyngeal swab will be obtained if any one of the following symptoms or signs is present: fever (≥38 C), cough, or shortness of breath, or if 2 of the following are present: fatigue, myalgia, headache, dizziness, expectoration, sore throat, diarrhea, nausea, vomiting, abdominal pain, runny nose, altered taste or smell, conjunctivitis, or painful swallowing. Participants that receive a COVID-19 vaccine after enrollment with efficacy of > 50% for the circulating strain will continue to be followed until 2 weeks after the first dose of the vaccine. All other participants will be followed for 10 weeks. Self-reporting of hand hygiene and the use of external monitors, where feasible, will be used to collect basic hand hygiene data. The sample size is 1,010 participants. This will allow 90% power at an alpha (one sided) of 0.05 and to account for participants who may not have completed 10 weeks because of COVID-19 mRNA vaccination. Changes made to the protocol prior to May 4, 2020, which was prior to the start of enrollment: Eligibility criteria expanded from nurses who provide direct patient care to health care workers that provide direct patient care. Allowed extended and re-use of N95 respirators if the local situation required it. Added self-reporting of hand hygiene and the use of external monitors if feasible. Reduced the duration of follow up from 12 weeks to 10 weeks Changes made on or after May 4, 2020: Expanded the criteria for the requirement of swabs to detect COVID-19 by adding runny nose, altered taste or smell, and conjunctivitis and also asked for a swab for fever, cough, or shortness of breath alone OR for two of the previously listed symptoms or signs (May 19, 2020). Added previously known COVID infection as an exclusion (October, 30, 2020). Added receipt of a COVID-19 vaccine with efficacy of > 50% as an exclusion (October 30, 2020). Allowed those participants that received a COVID-19 vaccine after enrollment with efficacy of > 50% for the circulating strain to continue to be followed until 2 weeks after the first dose of the vaccine (December 17, 2020). Increased the sample size to 1,010 participants to allow 90% power at an alpha (one sided) of 0.05 and to account for participants who may not have completed 10 weeks because of COVID-19 mRNA vaccination (July 26, 2021). Added wording to capture implementation since May 4th, 2020, Where the policy of the healthcare setting has been universal use of a facemask, that is wearing a facemask at all times when in the hospital, then the facemask participants were randomized to will be used. (December 27, 2021)
Official Title
-----------------
Medical Masks Versus N95 Respirators to Prevent 2019 Novel Coronavirus Disease (COVID-19) in Healthcare Workers: A Randomized Trial
Conditions
-----------------
N95, Coronavirus, Medical Mask
Intervention / Treatment
-----------------
* Device: Medical Mask
* Device: N95 respirator
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Health care workers who provide direct care to patients with suspected or confirmed COVID-19 in specialized COVID-19 units and in emergency departments, medical units, pediatric units, and long-term care facilities Health care workers are required to spend 60% or more of their time doing clinical work when enrolled. Exclusion Criteria: Unable to pass or do not have a valid fit test within the past 24 months One or more high-risk comorbidities for COVID-19 (hypertension, cardiac disease, pulmonary disease, chronic kidney disease, diabetes, chronic liver disease, actively treated cancer, or immunosuppression due to illness or medications) Previous laboratory confirmed clinical diagnosis of COVID-19 at the time of Received 1 or more doses of a COVID-19 vaccine with greater than 50% efficacy for the circulating strain (for example, mRNA or vector-based COVID-19 vaccine against the original SARS-CoV-2 strain). working in intensive care units.
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
Interventional Model Description: pragmatic, randomized, open-label, multicentre, noninferiority trial.
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medical Mask<br>Medical Mask worn when providing care to patient with febrile respiratory illness | Device: Medical Mask<br>* Medical Mask (known also as Surgical Mask)<br>|
| Active Comparator: N95 respirator<br>N95 respirator worn when providing care to patient with febrile respiratory illness | Device: N95 respirator<br>* N95 respirator<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RT-PCR confirmed COVID-19 infection | Number of participants with RT-PCR confirmed COVID-19 infection | 10 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute respiratory illness | Number of participants with acute respiratory illness | 10 weeks |
| Absenteeism | Number of participants with absenteeism | 10 weeks |
| Lower respiratory infection | Number of participants with lower respiratory infection | 10 weeks |
| Pneumonia | Number of participants with pneumonia | 10 weeks |
| ICU admission | Number of participants with ICU admission | 10 weeks |
| Mechanical ventilation | Number of participants needing mechanical ventilation | 10 weeks |
| Death | Number of participants that died | 10 weeks |
|
|
NCT00274105
|
SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients
|
The aim of this trial is to evaluate the efficacy and safety of telmisartan 80 mg administered once daily in patients with documented coronary artery disease (CAD) and a probably cardiovascular risk profile concerning the amelioration of structural alterations and endothelial function.~The primary objective of this trial is to evaluate the efficacy in particular with regard to the percentage change of atheroma volume in the femoral artery.The secondary objective is to evaluate the change in the plaque size- assessed by intravascular ultrasound, the increase in Flow Dependent Dilation provoked by intraarterial infusion of three increasing concentrations of Acetylcholine, and the change in seated systolic blood pressure.~Endothelial dysfunction is a primary event in atherogenesis and all known cardiovascular risk factors have been associated with endothelial dysfunction before atherosclerotic vascular disease manifests itself clinically. Pivotal to endothelial dysfunction is a disturbance in the function of endothelium-derived nitric oxide (NO). Recently, it could be shown that acute and chronic angiotensin-1 receptor antagonism reversed endothelial dysfunction in atherosclerosis. In experimental atherosclerosis, AT1 receptor blockade appears to have protective effects. Respective potential mechanisms include the prevention of endothelial injury, the augmentation of NO activity, the inhibition of lipid peroxidation and an antiproliferative effect. These findings together with the most recent data that losartan improves endothelial function and NO activity suggest that AT1 receptor antagonism may also be antiatherogenic in patients with atherosclerosis. Angiotensin II influences smooth muscle cell migration, hyperplasia, and hypertrophy. Angiotensin II also enhances production of local superoxide anion, which will inactivate nitric oxide. Inhibition of these reactions by the AT1-Blocker telmisartan may therefore interfere with atherosclerotic plaque formation.
|
Methodology:~2:1 randomised, double-blind and placebo-controlled parallel-group design~Planned/actual number of subjects:~Enrolled: 30/33, randomised: 30/22, completed: 30/15~Duration of treatment:~9 months: telmisartan (80 mg) or Placebo (80 mg)~Study Hypothesis:~The trial is designed as a group comparison of telmisartan 80 mg and placebo, where the treatment groups are randomised in 2:1 relation, to investigate the efficacy of telmisartan on structural alterations and endothelial dysfunction as measured as the percentage change from baseline after 36 weeks of treatment of the atheroma volume in the femoral artery using IVUS .~Secondary endpoints are the changes from baseline in the flow dependent dilatation after a acetylcholine challenge which follows a nitro-glycerin bolus, the change of the total atheroma volume, the percentage atheroma volume measured by intravascular ultrasound (IVUS) and the infalmmatory parameters MCP-1, CRP, ox LDL antibodies and sPLA2 activity and amount.~In an analysis of covariance using baseline as covariate all endpoints will be investigated. If the assumptions of normal distribution are not fulfilled, nonparametric methods will be applied (Wilcoxon-Mann-Whitney test).~Comparison(s):~Placebo 80 mg
|
A Double Blind, 2:1 Randomised Monocentre Study to Investigate the Efficacy and Safety of Telmisartan (80 mg qd) Concerning the Amelioration of Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients (SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients)
|
Hypertension, Coronary Arteriosclerosis
|
* Drug: telmisartan
* Drug: Placebo
|
Inclusion criteria:~> 35 years of age~History of coronary artery disease (CAD)~Ability to provide written informed consent~Exclusion criteria:~Pre-menopausal women (last menstruation < 1 year prior to start of the screening visit) who:~are not surgically sterile; and/or~are nursing~are of child-bearing potential and are NOT practising acceptable means of birth control, do NOT plan to continue using this method throughout the study and do NOT agree to submit to periodic pregnancy testing during participation in studies of > 3-months duration. Acceptable methods of birth control include oral, implantable or injectable contraceptives~Diastolic blood pressure > 110 mmHg or systolic blood pressure > 180 mmHg at any visit during the study (run-in or randomised period)~Hepatic and/or renal dysfunction as defined by the following laboratory parameters:~SGPT(ALT) or SGOT(AST) > than 2 times the upper limit of normal range~Serum creatinine > 2.3 mg/dL~Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients post-renal transplant or with only one kidney~Clinically relevant hypokalaemia or hyperkalaemia~Uncorrected volume depletion~Uncorrected sodium depletion~Primary aldosteronism~Hereditary fructose intolerance~Biliary obstructive disorders~Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin II receptor antagonists~History of drug or alcohol dependency within 6 months~Chronic administration of any medications known to affect blood pressure, except medication allowed by the protocol~Any investigational therapy within one month of signing the informed consent form~Known hypersensitivity to any component of the formulation~Any other clinical condition which, in the opinion of the principal investigator, would not allow safe completion of the protocol and safe administration of telmisartan~Stroke within the last 6 months~Myocardial infarction within the last 30 days~Cardiac surgery within the last 3 months~Hyperthyroidosis~Hemodynamically relevant valvular disease~Restrictive hypertrophic cardiomyopathy~Unstable angina pectoris~CAD with the indication of bypass surgery.
|
36 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of intima/media ratio in the femoral artery measured by intravascular ultrasound (IVUS) | | after 39 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plaque size in the femoral artery measured by IVUS | | after 39 weeks |
| Increase in FDD (Flow dependent dilation) stimulated by intra-arterial infusion of Acetylcholine (ACH) | | after 39 weeks |
| Change in serum inflammatory markers (CRP, MCP-1, oxLDL antibodies, and VCAM) | | after 39 weeks |
| Change in seated blood pressure (BP) at trough | | after 39 weeks |
|
Telmisartan, Antihypertensive Agents, Angiotensin II Type 1 Receptor Blockers, Angiotensin Receptor Antagonists, Molecular Mechanisms of Pharmacological Action
|
| Intervention/Treatment |
| --- |
|Drug: telmisartan|nan|
|Drug: Placebo|nan|
|
SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients
Study Overview
=================
Brief Summary
-----------------
The aim of this trial is to evaluate the efficacy and safety of telmisartan 80 mg administered once daily in patients with documented coronary artery disease (CAD) and a probably cardiovascular risk profile concerning the amelioration of structural alterations and endothelial function. The primary objective of this trial is to evaluate the efficacy in particular with regard to the percentage change of atheroma volume in the femoral artery.The secondary objective is to evaluate the change in the plaque size- assessed by intravascular ultrasound, the increase in Flow Dependent Dilation provoked by intraarterial infusion of three increasing concentrations of Acetylcholine, and the change in seated systolic blood pressure. Endothelial dysfunction is a primary event in atherogenesis and all known cardiovascular risk factors have been associated with endothelial dysfunction before atherosclerotic vascular disease manifests itself clinically. Pivotal to endothelial dysfunction is a disturbance in the function of endothelium-derived nitric oxide (NO). Recently, it could be shown that acute and chronic angiotensin-1 receptor antagonism reversed endothelial dysfunction in atherosclerosis. In experimental atherosclerosis, AT1 receptor blockade appears to have protective effects. Respective potential mechanisms include the prevention of endothelial injury, the augmentation of NO activity, the inhibition of lipid peroxidation and an antiproliferative effect. These findings together with the most recent data that losartan improves endothelial function and NO activity suggest that AT1 receptor antagonism may also be antiatherogenic in patients with atherosclerosis. Angiotensin II influences smooth muscle cell migration, hyperplasia, and hypertrophy. Angiotensin II also enhances production of local superoxide anion, which will inactivate nitric oxide. Inhibition of these reactions by the AT1-Blocker telmisartan may therefore interfere with atherosclerotic plaque formation.
Detailed Description
-----------------
Methodology: 2:1 randomised, double-blind and placebo-controlled parallel-group design Planned/actual number of subjects: Enrolled: 30/33, randomised: 30/22, completed: 30/15 Duration of treatment: 9 months: telmisartan (80 mg) or Placebo (80 mg) Study Hypothesis: The trial is designed as a group comparison of telmisartan 80 mg and placebo, where the treatment groups are randomised in 2:1 relation, to investigate the efficacy of telmisartan on structural alterations and endothelial dysfunction as measured as the percentage change from baseline after 36 weeks of treatment of the atheroma volume in the femoral artery using IVUS . Secondary endpoints are the changes from baseline in the flow dependent dilatation after a acetylcholine challenge which follows a nitro-glycerin bolus, the change of the total atheroma volume, the percentage atheroma volume measured by intravascular ultrasound (IVUS) and the infalmmatory parameters MCP-1, CRP, ox LDL antibodies and sPLA2 activity and amount. In an analysis of covariance using baseline as covariate all endpoints will be investigated. If the assumptions of normal distribution are not fulfilled, nonparametric methods will be applied (Wilcoxon-Mann-Whitney test). Comparison(s): Placebo 80 mg
Official Title
-----------------
A Double Blind, 2:1 Randomised Monocentre Study to Investigate the Efficacy and Safety of Telmisartan (80 mg qd) Concerning the Amelioration of Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients (SAFE-CRP: Structural Alterations and Function of Endothelium in Cardiovascular Risk Patients)
Conditions
-----------------
Hypertension, Coronary Arteriosclerosis
Intervention / Treatment
-----------------
* Drug: telmisartan
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: > 35 years of age History of coronary artery disease (CAD) Ability to provide written informed consent Exclusion criteria: Pre-menopausal women (last menstruation < 1 year prior to start of the screening visit) who: are not surgically sterile; and/or are nursing are of child-bearing potential and are NOT practising acceptable means of birth control, do NOT plan to continue using this method throughout the study and do NOT agree to submit to periodic pregnancy testing during participation in studies of > 3-months duration. Acceptable methods of birth control include oral, implantable or injectable contraceptives Diastolic blood pressure > 110 mmHg or systolic blood pressure > 180 mmHg at any visit during the study (run-in or randomised period) Hepatic and/or renal dysfunction as defined by the following laboratory parameters: SGPT(ALT) or SGOT(AST) > than 2 times the upper limit of normal range Serum creatinine > 2.3 mg/dL Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, patients post-renal transplant or with only one kidney Clinically relevant hypokalaemia or hyperkalaemia Uncorrected volume depletion Uncorrected sodium depletion Primary aldosteronism Hereditary fructose intolerance Biliary obstructive disorders Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin II receptor antagonists History of drug or alcohol dependency within 6 months Chronic administration of any medications known to affect blood pressure, except medication allowed by the protocol Any investigational therapy within one month of signing the informed consent form Known hypersensitivity to any component of the formulation Any other clinical condition which, in the opinion of the principal investigator, would not allow safe completion of the protocol and safe administration of telmisartan Stroke within the last 6 months Myocardial infarction within the last 30 days Cardiac surgery within the last 3 months Hyperthyroidosis Hemodynamically relevant valvular disease Restrictive hypertrophic cardiomyopathy Unstable angina pectoris CAD with the indication of bypass surgery.
Ages Eligible for Study
-----------------
Minimum Age: 36 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
| Intervention/Treatment |
| --- |
|Drug: telmisartan|nan|
|Drug: Placebo|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of intima/media ratio in the femoral artery measured by intravascular ultrasound (IVUS) | | after 39 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plaque size in the femoral artery measured by IVUS | | after 39 weeks |
| Increase in FDD (Flow dependent dilation) stimulated by intra-arterial infusion of Acetylcholine (ACH) | | after 39 weeks |
| Change in serum inflammatory markers (CRP, MCP-1, oxLDL antibodies, and VCAM) | | after 39 weeks |
| Change in seated blood pressure (BP) at trough | | after 39 weeks |
|
|
NCT05401890
|
Association Between Serum Ferritin Level and Severity of Liver Disease and Development of HCC in Cirrhotic Patients
|
Association between serum ferritin level and severity of liver disease and development of HCC in cirrhotic patients .
|
th leading cause of cancer mortality worldwide, with an estimated 841,000 (9.3 cases per 100,000 person-years) and 782,000 deaths (8.5 deaths per 100,000 person-years) in 2018.(Bray F et al., 2018) In Egypt, it represents the fourth common cancer and the leading cause of mortality- and morbidity-related cancer .(Akinyemiju T, et al.T 2017) Many hospital based studies reported increasing the incidence of HCC The reason for increased incidence could be attributed to improvement in screening programs and diagnostic tools, increasing the survival rate of cirrhotic patients that increases the chance of developing HCC . (Ibrahim AS, et al 2014) Because the early stage disease is usually asymptomatic, approximate half of patients are diagnosed at an advanced stage. Many biomarkers, such as α-fetoprotein (AFP) have already been used to screen for HCC and choose the best treatment on an individual status. However, these biomarkers are not sufficient to predict prognosis accurately. (Kabbach G, 2015) Ferritin, as a soluble iron-storage protein, participates in iron metabolism and accumulation, which directly damage DNA and proteins by generating reactive species and cause apoptosis through activation of the caspase cascade and hyperoxidation of fatty chains(Miyanishi K et al., 2019). Additionally, it is believed to be responsible for enhanced production of collagen and liver fibrosis . (Wang W et al., 2010) Elevated serum ferritin is frequently observed among patients with liver injury, regardless of etiology. (Wong K, Adams PC, 2006) However, whether ferritin is associated with incident liver cancer remains unclear. On one hand, previous clinical and epidemiologic studies show that serum ferritin may be correlated with liver cancer risk. For example, a recent meta-analysis including nine studies showed that higher serum ferritin was associated with 1.5-fold increases in risk of liver cancer. (Tran KT et al., 2019) On the other hand, the serum ferritin levels were associated with liver cancer among HCV+ men but not women in a Japanese cohort study. (Uchino K et al 2016 ) Moreover, no study has evaluated association between serum ferritin levels and the severity of hepatic decompensation in cirrhotic patients. Therefore, we will carry out a case-control study in Al Rajhy Liver Hospital, Assiut University, to examine the association between serum ferritin concentration and the incidence of HCC and severity of hepatic impairment in subjects with liver cirrhosis.
|
Association Between Serum Ferritin Level and Severity of Liver Disease and Development of HCC in Cirrhotic Patients.
|
HCC
|
Inclusion Criteria:~Patients with liver cirrhosis of both sexes with and without HCC regardless of the aetiology of chronic liver disease~Exclusion Criteria:~Patients less than 18 years Previously treated HCC patients with no evidence of recurrence or residual activity Subjects who had received blood transfusions or iron supplements during the previous 3 months.~Other conditions associated with elevated serum ferritin e.g., malignancy other than HCC, iron overload syndromes, autoimmune disorders, chronic excess alcohol consumption and acute and chronic infections.~Patients who will refuse to give a written consent, will be excluded from our study
|
18 Years
|
75 Years
|
All
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between serum ferritin level and severity of liver disease and development of HCC in cirrhotic patients . | The relation between serum ferritin level and severity of liver disease and development of HCC in cirrhotic patients | One year |
|
Liver Diseases, Digestive System Diseases
|
Association Between Serum Ferritin Level and Severity of Liver Disease and Development of HCC in Cirrhotic Patients
Study Overview
=================
Brief Summary
-----------------
Association between serum ferritin level and severity of liver disease and development of HCC in cirrhotic patients .
Detailed Description
-----------------
th leading cause of cancer mortality worldwide, with an estimated 841,000 (9.3 cases per 100,000 person-years) and 782,000 deaths (8.5 deaths per 100,000 person-years) in 2018.(Bray F et al., 2018) In Egypt, it represents the fourth common cancer and the leading cause of mortality- and morbidity-related cancer .(Akinyemiju T, et al.T 2017) Many hospital based studies reported increasing the incidence of HCC The reason for increased incidence could be attributed to improvement in screening programs and diagnostic tools, increasing the survival rate of cirrhotic patients that increases the chance of developing HCC . (Ibrahim AS, et al 2014) Because the early stage disease is usually asymptomatic, approximate half of patients are diagnosed at an advanced stage. Many biomarkers, such as α-fetoprotein (AFP) have already been used to screen for HCC and choose the best treatment on an individual status. However, these biomarkers are not sufficient to predict prognosis accurately. (Kabbach G, 2015) Ferritin, as a soluble iron-storage protein, participates in iron metabolism and accumulation, which directly damage DNA and proteins by generating reactive species and cause apoptosis through activation of the caspase cascade and hyperoxidation of fatty chains(Miyanishi K et al., 2019). Additionally, it is believed to be responsible for enhanced production of collagen and liver fibrosis . (Wang W et al., 2010) Elevated serum ferritin is frequently observed among patients with liver injury, regardless of etiology. (Wong K, Adams PC, 2006) However, whether ferritin is associated with incident liver cancer remains unclear. On one hand, previous clinical and epidemiologic studies show that serum ferritin may be correlated with liver cancer risk. For example, a recent meta-analysis including nine studies showed that higher serum ferritin was associated with 1.5-fold increases in risk of liver cancer. (Tran KT et al., 2019) On the other hand, the serum ferritin levels were associated with liver cancer among HCV+ men but not women in a Japanese cohort study. (Uchino K et al 2016 ) Moreover, no study has evaluated association between serum ferritin levels and the severity of hepatic decompensation in cirrhotic patients. Therefore, we will carry out a case-control study in Al Rajhy Liver Hospital, Assiut University, to examine the association between serum ferritin concentration and the incidence of HCC and severity of hepatic impairment in subjects with liver cirrhosis.
Official Title
-----------------
Association Between Serum Ferritin Level and Severity of Liver Disease and Development of HCC in Cirrhotic Patients.
Conditions
-----------------
HCC
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with liver cirrhosis of both sexes with and without HCC regardless of the aetiology of chronic liver disease Exclusion Criteria: Patients less than 18 years Previously treated HCC patients with no evidence of recurrence or residual activity Subjects who had received blood transfusions or iron supplements during the previous 3 months. Other conditions associated with elevated serum ferritin e.g., malignancy other than HCC, iron overload syndromes, autoimmune disorders, chronic excess alcohol consumption and acute and chronic infections. Patients who will refuse to give a written consent, will be excluded from our study
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years
Sexes Eligible for Study
-----------------
All
Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between serum ferritin level and severity of liver disease and development of HCC in cirrhotic patients . | The relation between serum ferritin level and severity of liver disease and development of HCC in cirrhotic patients | One year |
|
|||||
NCT05524376
|
Regulatory Network and Diagnostic Value of Key Autophagy-related Genes in Sepsis
|
Autophagy plays an important role in the occurrence and development of sepsis. This study aims to explore and verify the key autophagy-related genes in sepsis, then construct their regulatory networks and evaluate their potential diagnostic value, so as to provide new ideas for the diagnosis and treatment of sepsis.
|
(1) Sepsis-related datasets GSE65682,GSE134347 and GSE134358 were downloaded from GEO database, and DEmRNA,DElncRNA and DEmiRNA were obtained by differential analysis. (2) Autophagy related genes (ARGs) were obtained from Human Autophagy Database, and ARGs in GSE65682 and GSE134347 were extracted. DEARGs were obtained by differential analysis, and GO and KEGG enrichment analysis were performed. (3) Sepsis-related genes were obtained by WGCNA analysis, and key DEARGs in sepsis were obtained by intersection with DEARGs, and then transcription factors and ceRNA regulatory network were analyzed. (4) Immune infiltration analysis was used to evaluate the distribution of immune cells in the blood of patients with sepsis, and its correlation with key DEARGs was further analyzed. (5) The diagnostic functions of key DEARGs were analyzed. (6) Peripheral blood samples from sepsis patients and healthy controls were collected and verified by RT-qPCR.
|
Regulatory Network and Diagnostic Value of Key Autophagy-related Genes in Sepsis
|
Sepsis, Autophagy
|
* Other: no intervention
|
Inclusion Criteria:1) over 18 years old; 2) Meeting the diagnostic criteria of Sepsis 3.0; 3) Hospital stay longer than 24 hours.~Exclusion Criteria:1) Malignant tumor; 2) Autoimmune diseases; 3) Use of immunosuppressants in the past two weeks; 4) Readmission or transfer from another ICU due to the same disease.
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic Value of Key Autophagy-related Genes in Sepsis | The diagnostic functions of key DEARGs (Differential Autophagy-related Genes) were analyzed | October 2022 |
| Regulatory Network of Key Autophagy-related Genes in Sepsis | Key DEARGs in sepsis were analyzed for transcription factors and ceRNA regulatory network | October 2022 |
| Verified Key Autophagy-related Genes in Sepsis by RT-qPCR. | Peripheral blood samples from sepsis patients and healthy controls were collected and verified by RT-qPCR. | December 2022 |
|
sepsis, autophagy
|
Sepsis, Toxemia, Infections, Systemic Inflammatory Response Syndrome, Inflammation, Pathologic Processes
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| sepsis group<br> | Other: no intervention<br>* no intervention<br>|
| control group<br> | Other: no intervention<br>* no intervention<br>|
|
Regulatory Network and Diagnostic Value of Key Autophagy-related Genes in Sepsis
Study Overview
=================
Brief Summary
-----------------
Autophagy plays an important role in the occurrence and development of sepsis. This study aims to explore and verify the key autophagy-related genes in sepsis, then construct their regulatory networks and evaluate their potential diagnostic value, so as to provide new ideas for the diagnosis and treatment of sepsis.
Detailed Description
-----------------
(1) Sepsis-related datasets GSE65682,GSE134347 and GSE134358 were downloaded from GEO database, and DEmRNA,DElncRNA and DEmiRNA were obtained by differential analysis. (2) Autophagy related genes (ARGs) were obtained from Human Autophagy Database, and ARGs in GSE65682 and GSE134347 were extracted. DEARGs were obtained by differential analysis, and GO and KEGG enrichment analysis were performed. (3) Sepsis-related genes were obtained by WGCNA analysis, and key DEARGs in sepsis were obtained by intersection with DEARGs, and then transcription factors and ceRNA regulatory network were analyzed. (4) Immune infiltration analysis was used to evaluate the distribution of immune cells in the blood of patients with sepsis, and its correlation with key DEARGs was further analyzed. (5) The diagnostic functions of key DEARGs were analyzed. (6) Peripheral blood samples from sepsis patients and healthy controls were collected and verified by RT-qPCR.
Official Title
-----------------
Regulatory Network and Diagnostic Value of Key Autophagy-related Genes in Sepsis
Conditions
-----------------
Sepsis, Autophagy
Intervention / Treatment
-----------------
* Other: no intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria:1) over 18 years old; 2) Meeting the diagnostic criteria of Sepsis 3.0; 3) Hospital stay longer than 24 hours. Exclusion Criteria:1) Malignant tumor; 2) Autoimmune diseases; 3) Use of immunosuppressants in the past two weeks; 4) Readmission or transfer from another ICU due to the same disease.
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| sepsis group<br> | Other: no intervention<br>* no intervention<br>|
| control group<br> | Other: no intervention<br>* no intervention<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic Value of Key Autophagy-related Genes in Sepsis | The diagnostic functions of key DEARGs (Differential Autophagy-related Genes) were analyzed | October 2022 |
| Regulatory Network of Key Autophagy-related Genes in Sepsis | Key DEARGs in sepsis were analyzed for transcription factors and ceRNA regulatory network | October 2022 |
| Verified Key Autophagy-related Genes in Sepsis by RT-qPCR. | Peripheral blood samples from sepsis patients and healthy controls were collected and verified by RT-qPCR. | December 2022 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sepsis, autophagy
|
||
NCT02534129
|
Topical Use of Difinsa53™ to Prevent Radiation Dermatitis
|
Phase II trial of the silibin containing cream, Difinsa53 to determine efficacy in delaying, ameliorating, or preventing radiation dermatitis in patients with breast cancer undergoing whole breast radiation.
|
The proposed study seeks to evaluate the efficacy of DIFINISA53™, a safe silibin-based skin cream, on preventing radiation dermatitis (RD) when compared to an over the counter ointment, Aquaphor, in women undergoing radiation therapy for breast cancer following lumpectomy or mastectomy surgery. Presently there is no known fully effective topical protectant from RD and there is no consensus among radiation oncologists on how best to treat RD. This study seeks to identify a more effective option for patients receiving radiation therapy. Each participant will apply the DIFINISA53™ cream to one area of the treated skin and Aquaphor to another area of treated skin. Skin reactions will be evaluated using medical professional assessment, participant assessment, and photographic assessment by a third party.
|
Topical Use of a Silibin-based Cream, Difinsa53™, to Prevent Radiation Dermatitis in Patients With Breast Cancer: A Prospective Study
|
Radiodermatitis
|
* Drug: Difinsa53
* Drug: Aquaphor
|
Inclusion Criteria:~Female patients 18 years and older~Pathologic diagnosis of breast cancer requiring radiation therapy to whole breast~Able to apply lotion to treatment area at least twice daily during radiation course~All surgical sites healed~No evidence of infection~No history of sensitivity to any component in Aquaphor or Difensa53~Exclusion Criteria:~Prior history of radiation therapy (RT) to that site~Known dermatologic conditions affecting skin in radiation port~Concurrent chemotherapy~Skin infection in radiation port~History of sensitivity to Aquaphor or Difensa53 component
| null | null |
Female
|
No
|
Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiation Dermatitis as Determined by Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria | A blinded observer will quantify degree of dermatitis assigning each half of the radiation field a score from 0 to 4. 0 represents no dermatitis and 4 is severe dermatitis using the RTOG scoring criteria. | 8 weeks |
|
dermatitis, breast cancer, radiation
|
Petrolatum, Emollients, Dermatologic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>Radiation field is divided into two sections, one treated with Difinsa53 and the other with Aquaphor | Drug: Difinsa53<br>* Difinsa53 cream is applied to one half of radiation field<br>* Other names: Dimethicone;Drug: Aquaphor<br>* Aquaphor is applied to one half of radiation field<br>* Other names: petrolatum;|
|
Topical Use of Difinsa53™ to Prevent Radiation Dermatitis
Study Overview
=================
Brief Summary
-----------------
Phase II trial of the silibin containing cream, Difinsa53 to determine efficacy in delaying, ameliorating, or preventing radiation dermatitis in patients with breast cancer undergoing whole breast radiation.
Detailed Description
-----------------
The proposed study seeks to evaluate the efficacy of DIFINISA53™, a safe silibin-based skin cream, on preventing radiation dermatitis (RD) when compared to an over the counter ointment, Aquaphor, in women undergoing radiation therapy for breast cancer following lumpectomy or mastectomy surgery. Presently there is no known fully effective topical protectant from RD and there is no consensus among radiation oncologists on how best to treat RD. This study seeks to identify a more effective option for patients receiving radiation therapy. Each participant will apply the DIFINISA53™ cream to one area of the treated skin and Aquaphor to another area of treated skin. Skin reactions will be evaluated using medical professional assessment, participant assessment, and photographic assessment by a third party.
Official Title
-----------------
Topical Use of a Silibin-based Cream, Difinsa53™, to Prevent Radiation Dermatitis in Patients With Breast Cancer: A Prospective Study
Conditions
-----------------
Radiodermatitis
Intervention / Treatment
-----------------
* Drug: Difinsa53
* Drug: Aquaphor
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female patients 18 years and older Pathologic diagnosis of breast cancer requiring radiation therapy to whole breast Able to apply lotion to treatment area at least twice daily during radiation course All surgical sites healed No evidence of infection No history of sensitivity to any component in Aquaphor or Difensa53 Exclusion Criteria: Prior history of radiation therapy (RT) to that site Known dermatologic conditions affecting skin in radiation port Concurrent chemotherapy Skin infection in radiation port History of sensitivity to Aquaphor or Difensa53 component
Sexes Eligible for Study
-----------------
Female
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>Radiation field is divided into two sections, one treated with Difinsa53 and the other with Aquaphor | Drug: Difinsa53<br>* Difinsa53 cream is applied to one half of radiation field<br>* Other names: Dimethicone;Drug: Aquaphor<br>* Aquaphor is applied to one half of radiation field<br>* Other names: petrolatum;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiation Dermatitis as Determined by Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria | A blinded observer will quantify degree of dermatitis assigning each half of the radiation field a score from 0 to 4. 0 represents no dermatitis and 4 is severe dermatitis using the RTOG scoring criteria. | 8 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
dermatitis, breast cancer, radiation
|
|
NCT04799353
|
Study to Evaluate the Safety and How the Body Handles a Single Dose of Subcutaneous (SC) and Intravenous (IV) Budigalimab in Adult Participants Living With Human Immunodeficiency Virus (HIV)
|
This study will evaluate how safe Budigalimab is and how it moves within the body in adult participants with HIV-1 infection.~Budigalimab is an investigational drug being evaluated for the treatment of Human Immunodeficiency Virus. Study participants will be assigned to one of the 4 treatment groups and will receive a single dose of Budigalimab or placebo subcutaneous (SC) and intravenous (IV). Around 32 participants 18-65 years of age living with Human Immunodeficiency Virus will be enrolled in the study in approximately 9 sites worldwide.~Each participant will receive single dose of SC and IV Budigalimab and/or Placebo on day 1 and will be followed for 24 weeks.~Participants will attend weekly to every two and every four weeks visits during the study at a hospital. The effect of the treatment will be checked by medical assessments, blood tests and checking for side effects. There may be higher treatment burden for participants in this trial.
|
A Randomized, Double-Blind, Placebo-controlled Single-Dose Phase 1b Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous and Intravenous Administration of Budigalimab in Adult People Living With HIV-1 (PLWH)
|
Human Immunodeficiency Virus (HIV)
|
* Drug: Budigalimab
* Drug: Placebo
* Drug: Budigalimab
* Drug: Placebo
|
Inclusion Criteria:~Condition of generally good health, body mass index ≥ 18.0 to < 35.0 kg/m2.~Laboratory values must meet acceptable criteria.~Human Immunodeficiency Virus (HIV-1) infected on antiretroviral therapy (ART) for at least 12 months prior to screening and on current ART regimen for at least 8 weeks prior to screening.~CD4 cell count ≥ 450 cells/μL at Screening and during the 12 months prior to Screening.~Plasma HIV-1 RNA below the lower limit of quantification at Screening and at least 6 months prior to Screening.~Participants agreeing to use an effective barrier method of protection (male and/or female condom) during sexual activity from Study Day 1 through last study visit for the purposes of prevention of HIV transmission.~Exclusion Criteria:~Participants with signs/symptoms associated with SARS-CoV-2 infection OR Current SARS-CoV-2 infection by any viral nucleic acid test completed within 7 days prior to the Day 1 dose.~Participants having history or ongoing diagnosis of acquired immunodeficiency syndrome (AIDS)-defining illness.~Participants having history of or active immunodeficiency (other than HIV).~Participants having active autoimmune disease or history of autoimmune disease that has required systemic treatment.~Prior therapy/exposure to budigalimab or any other immune checkpoint inhibitor [e.g., anti-programmed cell death protein 1(PD-1), anti-PD-L1, anti-PD-L2, anti-CTLA4].~Participants having clinically significant medical disorders that might expose the subjects to undue risk of harm, confound study outcomes, or prevent the subject from completing the study.~Participants having active or suspected malignancy or history of malignancy (other than basal cell skin cancer or cervical carcinoma in situ) in the past 5 years.~Participants with history of or active tuberculosis (TB) at screening.~Participants having known psychiatric or substance abuse disorders that would interfere with adherence to study requirements.~Participants who have received immunomodulatory or immunosuppressive (including IV/orally administered [PO] steroids at any dose, but excluding steroids that are inhaled, topical or via local injection) therapy within 24 weeks prior to the first dose of study drug.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Study Drug-Related Grade 3 or Higher Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of the study drug as either having a reasonable possibility or no reasonable possibility. AEs are given a grade from 1-5 with Grade 3 being severe but not life-threatening and requiring hospitalization, Grade 4 being life-threatening requiring immediate intervention and Grade 5 being death related to an AE. | Up to approximately 24 weeks |
| Number of Participants With Study Drug-Related Immune-Related Adverse Events (IRAE) | Assessed using the American Society of Clinical Oncology (ASCO) IRAE management guidelines [which utilizes the National Institutes of Health (NIH) Common Terminology Criteria for Adverse Events (CTCAE) grading scale] but modified, as applicable, according to the NIH Division of AIDS (DAIDS) (v2.1) AE grading scale. | Up to approximately 24 weeks |
| Maximum Serum Concentration (Cmax) | Maximum Serum Concentration (Cmax) of Budigalimab. | Up to approximately 24 weeks |
| Time to Maximum Observed Plasma Concentration (Tmax) | Time to Maximum Observed Plasma Concentration (Tmax) of Budigalimab. | Up to approximately 24 weeks |
| Area Under the Plasma Concentration-time Curve (AUC) of Budigalimab in Plasma | Area Under the Plasma Concentration-time Curve (AUC). | Up to approximately 24 weeks |
| Terminal Phase Elimination Half-life (t1/2) of Budigalimab in Plasma | Terminal phase elimination half-life (t1/2) | Up to approximately 24 weeks. |
|
Human Immunodeficiency Virus (HIV), Budigalimab, ABBV-181
|
Acquired Immunodeficiency Syndrome, HIV Infections, Immunologic Deficiency Syndromes, Immune System Diseases, Blood-Borne Infections, Communicable Diseases, Infections, Sexually Transmitted Diseases, Viral, Sexually Transmitted Diseases, Lentivirus Infections, Retroviridae Infections, RNA Virus Infections, Virus Diseases, Slow Virus Diseases, Genital Diseases, Urogenital Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Placebo SC + Placebo IV<br>Participants will receive Subcutaneous (SC) Placebo, followed by Intravenous (IV) Placebo. | Drug: Placebo<br>* Subcutaneous (SC)<br>Drug: Placebo<br>* Intravenous (IV)<br>|
| Experimental: Group 2: Budigalimab (SC) + Placebo IV<br>Participants will receive Subcutaneous (SC) Budigalimab, followed by Intravenous (IV) Placebo. | Drug: Budigalimab<br>* Subcutaneous (SC)<br>* Other names: ABBV-181;Drug: Placebo<br>* Intravenous (IV)<br>|
| Experimental: Group 3: Budigalimab SC + Placebo IV<br>Participants will receive Subcutaneous (SC) Budigalimab, followed by Intravenous (IV) Placebo. | Drug: Budigalimab<br>* Subcutaneous (SC)<br>* Other names: ABBV-181;Drug: Placebo<br>* Intravenous (IV)<br>|
| Experimental: Group 4: Placebo SC + Budigalimab IV<br>Participants will receive Subcutaneous (SC) Placebo, followed by IV Budigalimab. | Drug: Placebo<br>* Subcutaneous (SC)<br>Drug: Budigalimab<br>* Intravenous (IV)<br>* Other names: ABBV-181;|
|
Study to Evaluate the Safety and How the Body Handles a Single Dose of Subcutaneous (SC) and Intravenous (IV) Budigalimab in Adult Participants Living With Human Immunodeficiency Virus (HIV)
Study Overview
=================
Brief Summary
-----------------
This study will evaluate how safe Budigalimab is and how it moves within the body in adult participants with HIV-1 infection. Budigalimab is an investigational drug being evaluated for the treatment of Human Immunodeficiency Virus. Study participants will be assigned to one of the 4 treatment groups and will receive a single dose of Budigalimab or placebo subcutaneous (SC) and intravenous (IV). Around 32 participants 18-65 years of age living with Human Immunodeficiency Virus will be enrolled in the study in approximately 9 sites worldwide. Each participant will receive single dose of SC and IV Budigalimab and/or Placebo on day 1 and will be followed for 24 weeks. Participants will attend weekly to every two and every four weeks visits during the study at a hospital. The effect of the treatment will be checked by medical assessments, blood tests and checking for side effects. There may be higher treatment burden for participants in this trial.
Official Title
-----------------
A Randomized, Double-Blind, Placebo-controlled Single-Dose Phase 1b Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous and Intravenous Administration of Budigalimab in Adult People Living With HIV-1 (PLWH)
Conditions
-----------------
Human Immunodeficiency Virus (HIV)
Intervention / Treatment
-----------------
* Drug: Budigalimab
* Drug: Placebo
* Drug: Budigalimab
* Drug: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Condition of generally good health, body mass index ≥ 18.0 to < 35.0 kg/m2. Laboratory values must meet acceptable criteria. Human Immunodeficiency Virus (HIV-1) infected on antiretroviral therapy (ART) for at least 12 months prior to screening and on current ART regimen for at least 8 weeks prior to screening. CD4 cell count ≥ 450 cells/μL at Screening and during the 12 months prior to Screening. Plasma HIV-1 RNA below the lower limit of quantification at Screening and at least 6 months prior to Screening. Participants agreeing to use an effective barrier method of protection (male and/or female condom) during sexual activity from Study Day 1 through last study visit for the purposes of prevention of HIV transmission. Exclusion Criteria: Participants with signs/symptoms associated with SARS-CoV-2 infection OR Current SARS-CoV-2 infection by any viral nucleic acid test completed within 7 days prior to the Day 1 dose. Participants having history or ongoing diagnosis of acquired immunodeficiency syndrome (AIDS)-defining illness. Participants having history of or active immunodeficiency (other than HIV). Participants having active autoimmune disease or history of autoimmune disease that has required systemic treatment. Prior therapy/exposure to budigalimab or any other immune checkpoint inhibitor [e.g., anti-programmed cell death protein 1(PD-1), anti-PD-L1, anti-PD-L2, anti-CTLA4]. Participants having clinically significant medical disorders that might expose the subjects to undue risk of harm, confound study outcomes, or prevent the subject from completing the study. Participants having active or suspected malignancy or history of malignancy (other than basal cell skin cancer or cervical carcinoma in situ) in the past 5 years. Participants with history of or active tuberculosis (TB) at screening. Participants having known psychiatric or substance abuse disorders that would interfere with adherence to study requirements. Participants who have received immunomodulatory or immunosuppressive (including IV/orally administered [PO] steroids at any dose, but excluding steroids that are inhaled, topical or via local injection) therapy within 24 weeks prior to the first dose of study drug.
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: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Placebo SC + Placebo IV<br>Participants will receive Subcutaneous (SC) Placebo, followed by Intravenous (IV) Placebo. | Drug: Placebo<br>* Subcutaneous (SC)<br>Drug: Placebo<br>* Intravenous (IV)<br>|
| Experimental: Group 2: Budigalimab (SC) + Placebo IV<br>Participants will receive Subcutaneous (SC) Budigalimab, followed by Intravenous (IV) Placebo. | Drug: Budigalimab<br>* Subcutaneous (SC)<br>* Other names: ABBV-181;Drug: Placebo<br>* Intravenous (IV)<br>|
| Experimental: Group 3: Budigalimab SC + Placebo IV<br>Participants will receive Subcutaneous (SC) Budigalimab, followed by Intravenous (IV) Placebo. | Drug: Budigalimab<br>* Subcutaneous (SC)<br>* Other names: ABBV-181;Drug: Placebo<br>* Intravenous (IV)<br>|
| Experimental: Group 4: Placebo SC + Budigalimab IV<br>Participants will receive Subcutaneous (SC) Placebo, followed by IV Budigalimab. | Drug: Placebo<br>* Subcutaneous (SC)<br>Drug: Budigalimab<br>* Intravenous (IV)<br>* Other names: ABBV-181;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Study Drug-Related Grade 3 or Higher Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of the study drug as either having a reasonable possibility or no reasonable possibility. AEs are given a grade from 1-5 with Grade 3 being severe but not life-threatening and requiring hospitalization, Grade 4 being life-threatening requiring immediate intervention and Grade 5 being death related to an AE. | Up to approximately 24 weeks |
| Number of Participants With Study Drug-Related Immune-Related Adverse Events (IRAE) | Assessed using the American Society of Clinical Oncology (ASCO) IRAE management guidelines [which utilizes the National Institutes of Health (NIH) Common Terminology Criteria for Adverse Events (CTCAE) grading scale] but modified, as applicable, according to the NIH Division of AIDS (DAIDS) (v2.1) AE grading scale. | Up to approximately 24 weeks |
| Maximum Serum Concentration (Cmax) | Maximum Serum Concentration (Cmax) of Budigalimab. | Up to approximately 24 weeks |
| Time to Maximum Observed Plasma Concentration (Tmax) | Time to Maximum Observed Plasma Concentration (Tmax) of Budigalimab. | Up to approximately 24 weeks |
| Area Under the Plasma Concentration-time Curve (AUC) of Budigalimab in Plasma | Area Under the Plasma Concentration-time Curve (AUC). | Up to approximately 24 weeks |
| Terminal Phase Elimination Half-life (t1/2) of Budigalimab in Plasma | Terminal phase elimination half-life (t1/2) | Up to approximately 24 weeks. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Human Immunodeficiency Virus (HIV), Budigalimab, ABBV-181
|
||
NCT01866891
|
Effects of Physical Activity on the Microcirculation in Hemodialysis Patients
|
Chronic kidney disease (CKD) is associated with high level of peripheral arterial disease (PAD). This could lead wounds, infections then amputations or deaths by impairment of the peripheral cutaneous perfusion. Medical therapies are presently unable to cure, but only slow down these disorders. Impact of exercise and lower extremity PAD rehabilitation is decreased by the significant inactivity of the chronic hemodialysis patients. Recently, many studies have shown several various favorable effects of the perdialytic physical activity. There is currently no data about effects of the perdialytic activity on the lower extremity perfusion. The aim of this clinical study is to show the impact of three months perdialytic cycling on the microcirculation, in chronic hemodialysis patients. Primary outcome will be the increase of cutaneous perfusion, assessed by measuring transcutaneous oxygen pressure (tcPO2) on about twenty patients.
|
Effects of Regular Perdialytic Physical Activity on the Peripheral Microcirculation in Chronic Hemodialysis Patients
|
Hemodialysis Patients
|
* Other: Three months of regular perdialytic physical activity (cycling)
|
Inclusion Criteria:~Patients performing chronic hemodialysis for more than 3 months~Adult aged > or = 18 years old~Information letter delivered to subjects~Written free informed consent~Clinically stable patients~Voluntary patients to perform 30 minutes cycling per dialysis session~Social French Security Affiliated subjects~Exclusion Criteria:~Subjects without inclusion criteria~Pregnant women~Subjects protected by the law~Physical impossibility to achieve exercise~Medical contraindication to perform physical exercise
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase of cutaneous lower extremity perfusion. | | TcPO2 will be performed at the inclusion and just after the end of the three month study period |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular assessment : Doppler and Index of systolic blood pressure | | At the inclusion and after the end of the three month study period |
| Related quality of life | | at the inclusion and after the end of the three month study period |
| Appetite (score) | | at the inclusion and after the end of the three month study period |
| Daily activity (Seven days pedometers) | | at the inclusion and after the end of the three month study period |
| Protein intake (n-PCR) | | at the inclusion and after the end of the three month study period |
| nutritional biological status (creatinin, albumin and transthyretin protein level) | | at the inclusion and after the end of the three month study period |
| strength (handgrip test) | | at the inclusion and after the end of the three month study period |
|
hemodialysis, microcirculation, physical perdialytic activity, cycling
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm<br> | Other: Three months of regular perdialytic physical activity (cycling)<br>* Cycling, in lying position, at a rate of thirty minutes per dialysis session (three a week), regardless of performance<br>|
|
Effects of Physical Activity on the Microcirculation in Hemodialysis Patients
Study Overview
=================
Brief Summary
-----------------
Chronic kidney disease (CKD) is associated with high level of peripheral arterial disease (PAD). This could lead wounds, infections then amputations or deaths by impairment of the peripheral cutaneous perfusion. Medical therapies are presently unable to cure, but only slow down these disorders. Impact of exercise and lower extremity PAD rehabilitation is decreased by the significant inactivity of the chronic hemodialysis patients. Recently, many studies have shown several various favorable effects of the perdialytic physical activity. There is currently no data about effects of the perdialytic activity on the lower extremity perfusion. The aim of this clinical study is to show the impact of three months perdialytic cycling on the microcirculation, in chronic hemodialysis patients. Primary outcome will be the increase of cutaneous perfusion, assessed by measuring transcutaneous oxygen pressure (tcPO2) on about twenty patients.
Official Title
-----------------
Effects of Regular Perdialytic Physical Activity on the Peripheral Microcirculation in Chronic Hemodialysis Patients
Conditions
-----------------
Hemodialysis Patients
Intervention / Treatment
-----------------
* Other: Three months of regular perdialytic physical activity (cycling)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients performing chronic hemodialysis for more than 3 months Adult aged > or = 18 years old Information letter delivered to subjects Written free informed consent Clinically stable patients Voluntary patients to perform 30 minutes cycling per dialysis session Social French Security Affiliated subjects Exclusion Criteria: Subjects without inclusion criteria Pregnant women Subjects protected by the law Physical impossibility to achieve exercise Medical contraindication to perform physical exercise
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: single arm<br> | Other: Three months of regular perdialytic physical activity (cycling)<br>* Cycling, in lying position, at a rate of thirty minutes per dialysis session (three a week), regardless of performance<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase of cutaneous lower extremity perfusion. | | TcPO2 will be performed at the inclusion and just after the end of the three month study period |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular assessment : Doppler and Index of systolic blood pressure | | At the inclusion and after the end of the three month study period |
| Related quality of life | | at the inclusion and after the end of the three month study period |
| Appetite (score) | | at the inclusion and after the end of the three month study period |
| Daily activity (Seven days pedometers) | | at the inclusion and after the end of the three month study period |
| Protein intake (n-PCR) | | at the inclusion and after the end of the three month study period |
| nutritional biological status (creatinin, albumin and transthyretin protein level) | | at the inclusion and after the end of the three month study period |
| strength (handgrip test) | | at the inclusion and after the end of the three month study period |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hemodialysis, microcirculation, physical perdialytic activity, cycling
|
||
NCT05150379
|
Influence of the Dominance of the Shoulder Stabilized by the Open Latarjet Procedure on the Functional Recovery of the Shoulder at 4.5 Months Postoperatively.
|
The aim of this study is to quantify the functional deficits as a function of the dominance of the shoulder stabilized by the open procedure of Latarjet at 4.5 months postoperatively compared to healthy controls.
|
Influence of the Dominance of the Shoulder Stabilized by the Open Latarjet Procedure on the Functional Recovery of the Shoulder at 4.5 Months Postoperatively: Patients Operated on the Dominant Side vs. Patients Operated on the Non-dominant Side vs. Healthy Controls
|
Latarjet, Shoulder Injuries
|
* Other: Different exercises with their shoulders
* Behavioral: SI-RSI questionnaire
|
Patients from two studies : Reproducibility of functional tests of the shoulder for the return to sport of patients operated on anterior instability of the shoulder CPP n ° 2018-A03013-52 and Validation of the S-STARTS composite score to assess the functions of the shoulder and the patient's ability to return to sport after stabilization of the shoulder by the Latarjet procedure (VAL-S-STARTS) MR3016020520~healthy volunteers from two studies : Reproducibility of functional tests of the shoulder for the return to sport of patients operated on anterior instability of the shoulder CPP n ° 2018-A03013-52 and Risk factors for shoulder dislocation in rugby players. Predictive validity of the S-STARTS composite score MR4612110620~Inclusion criteria:~Patients: o patient between 15 and 45 years old~Occurrence of the injury requiring surgery during a sports activity~Reduced shoulder instability by the open Latarjet procedure~Surgery performed by surgeons from the Santy Orthopedic Center (Lyon)~Inclusion by decision of the surgeon during the visit 4 months postoperatively~Healthy volunteers :~volunteer between 15 and 45 years old~Practice a regular sporting activity~Both groups:~Patient having signed an informed consent~Subject affiliated or beneficiary of a social security scheme~Exclusion Criteria:~Patient group:~Contraindication of the surgeon~Have another pathology in the upper limbs~Present a constitutional hyperlaxity~Have stiffness or recurrence of dislocation of the shoulder post-surgery~Healthy volunteers :~Medical history of upper limb pain / injury within the past 12 months~Medical history of orthopedic surgery on the upper limbs~Both groups:~Protected subject: adult under guardianship, curatorship or other legal protection, deprived of liberty by judicial or administrative decision
|
15 Years
|
45 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| S-STARTS composite score for each participant | Score between 0 and 21:~0: total functional disability~21: full functional ability | 1 hour |
|
Shoulder Injuries, Wounds and Injuries
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Dominant side shoulder surgery patients<br> | Other: Different exercises with their shoulders<br>* Y Balance Test~Shoulder rotator muscle isometric maximum strength~One handed medicine ball throw~Modified Closed Kinetic Chain Upper Extremity Stability Test<br>Behavioral: SI-RSI questionnaire<br>* French version of Shoulder Instability Return-to-Sport after Injury<br>|
| Patients operated on the shoulder on the non-dominant side<br> | Other: Different exercises with their shoulders<br>* Y Balance Test~Shoulder rotator muscle isometric maximum strength~One handed medicine ball throw~Modified Closed Kinetic Chain Upper Extremity Stability Test<br>Behavioral: SI-RSI questionnaire<br>* French version of Shoulder Instability Return-to-Sport after Injury<br>|
| Healthy volunteers<br> | Other: Different exercises with their shoulders<br>* Y Balance Test~Shoulder rotator muscle isometric maximum strength~One handed medicine ball throw~Modified Closed Kinetic Chain Upper Extremity Stability Test<br>Behavioral: SI-RSI questionnaire<br>* French version of Shoulder Instability Return-to-Sport after Injury<br>|
|
Influence of the Dominance of the Shoulder Stabilized by the Open Latarjet Procedure on the Functional Recovery of the Shoulder at 4.5 Months Postoperatively.
Study Overview
=================
Brief Summary
-----------------
The aim of this study is to quantify the functional deficits as a function of the dominance of the shoulder stabilized by the open procedure of Latarjet at 4.5 months postoperatively compared to healthy controls.
Official Title
-----------------
Influence of the Dominance of the Shoulder Stabilized by the Open Latarjet Procedure on the Functional Recovery of the Shoulder at 4.5 Months Postoperatively: Patients Operated on the Dominant Side vs. Patients Operated on the Non-dominant Side vs. Healthy Controls
Conditions
-----------------
Latarjet, Shoulder Injuries
Intervention / Treatment
-----------------
* Other: Different exercises with their shoulders
* Behavioral: SI-RSI questionnaire
Participation Criteria
=================
Eligibility Criteria
-----------------
Patients from two studies : Reproducibility of functional tests of the shoulder for the return to sport of patients operated on anterior instability of the shoulder CPP n ° 2018-A03013-52 and Validation of the S-STARTS composite score to assess the functions of the shoulder and the patient's ability to return to sport after stabilization of the shoulder by the Latarjet procedure (VAL-S-STARTS) MR3016020520 healthy volunteers from two studies : Reproducibility of functional tests of the shoulder for the return to sport of patients operated on anterior instability of the shoulder CPP n ° 2018-A03013-52 and Risk factors for shoulder dislocation in rugby players. Predictive validity of the S-STARTS composite score MR4612110620 Inclusion criteria: Patients: o patient between 15 and 45 years old Occurrence of the injury requiring surgery during a sports activity Reduced shoulder instability by the open Latarjet procedure Surgery performed by surgeons from the Santy Orthopedic Center (Lyon) Inclusion by decision of the surgeon during the visit 4 months postoperatively Healthy volunteers : volunteer between 15 and 45 years old Practice a regular sporting activity Both groups: Patient having signed an informed consent Subject affiliated or beneficiary of a social security scheme Exclusion Criteria: Patient group: Contraindication of the surgeon Have another pathology in the upper limbs Present a constitutional hyperlaxity Have stiffness or recurrence of dislocation of the shoulder post-surgery Healthy volunteers : Medical history of upper limb pain / injury within the past 12 months Medical history of orthopedic surgery on the upper limbs Both groups: Protected subject: adult under guardianship, curatorship or other legal protection, deprived of liberty by judicial or administrative decision
Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 45 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 |
| --- | --- |
| Dominant side shoulder surgery patients<br> | Other: Different exercises with their shoulders<br>* Y Balance Test Shoulder rotator muscle isometric maximum strength One handed medicine ball throw Modified Closed Kinetic Chain Upper Extremity Stability Test<br>Behavioral: SI-RSI questionnaire<br>* French version of Shoulder Instability Return-to-Sport after Injury<br>|
| Patients operated on the shoulder on the non-dominant side<br> | Other: Different exercises with their shoulders<br>* Y Balance Test Shoulder rotator muscle isometric maximum strength One handed medicine ball throw Modified Closed Kinetic Chain Upper Extremity Stability Test<br>Behavioral: SI-RSI questionnaire<br>* French version of Shoulder Instability Return-to-Sport after Injury<br>|
| Healthy volunteers<br> | Other: Different exercises with their shoulders<br>* Y Balance Test Shoulder rotator muscle isometric maximum strength One handed medicine ball throw Modified Closed Kinetic Chain Upper Extremity Stability Test<br>Behavioral: SI-RSI questionnaire<br>* French version of Shoulder Instability Return-to-Sport after Injury<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| S-STARTS composite score for each participant | Score between 0 and 21: 0: total functional disability 21: full functional ability | 1 hour |
|
||||
NCT03476746
|
Dermatopharmacokinetic Trial of LEO 90100 Foam
|
This is a phase 1, single centre trial in Japanese healthy male subjects comparing the amount of active ingredients of LEO 90100 foam and Dovobet® ointment in the stratum corneum.
|
Dermatopharmacokinetic Trial of LEO 90100 Foam
|
Healthy
|
* Drug: LEO 90100 foam
* Drug: Dovobet® ointment
|
Inclusion Criteria:~Healthy Japanese male subjects, aged 20 to 40 years inclusive~Exclusion Criteria:~Body Mass Index outside the range 18-25 kg/m²~Use of any medication (systemic or topical) within 2 weeks of Day 1.
|
20 Years
|
40 Years
|
Male
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: A single application of LEO 90100 foam and Dovobet® ointment will be applied to multiple test sites on the innerside of both arms of trial subjects. The trial consists of 2 parts. The first part, (pilot part) will evaluate the pharmacokinetic profile of LEO 90100 foam and Dovobet® ointment by measuring the amount of each of the active ingredients in the stratum corneum and determine conditions for the second part of the trial. The second part (pivotal part) will compare the amount of each of the active ingredients at steady state or close-to-steady state between LEO 90100 foam and Dovobet® ointment. The sample size and the number of application sites in the pivotal part will be determined based on the results of the pilot part.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount of each of the 2 active ingredients, calcipotriol and betamethasone dipropionate, in the stratum corneum obtained by means of tape stripping after application of LEO 90100 foam and Dovobet® ointment. | Amount (nanogram) of calcipotriol and betamethasone dipropionate in the stratum corneum will be compared between the two formulations by selected time points using an ANOVA model with treatment/formulation as systematic effect. | 2, 4, 6, 8, 12 and 24 hr after drug application. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety data - number of adverse events | Number of adverse events | up to 15 Days after drug application |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 90100 foam<br>LEO 90100 foam (containing calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g).~Pilot part: 6 single applications of LEO 90100 foam on Day 1 (for 12 sites in total).~Pivotal part: To be decided based on the result of the pilot part | Drug: LEO 90100 foam<br>* A foam formulation of the active comparator Dovobet® ointment<br>|
| Active Comparator: Dovobet® ointment<br>Pilot part: 6 single applications of Dovobet® ointment on Day 1 (for 12 sites in total).~Pivotal part: To be decided based on the result of the pilot part | Drug: Dovobet® ointment<br>* Ointment formulation containing same active ingredients as LEO 90100 foam<br>|
|
Dermatopharmacokinetic Trial of LEO 90100 Foam
Study Overview
=================
Brief Summary
-----------------
This is a phase 1, single centre trial in Japanese healthy male subjects comparing the amount of active ingredients of LEO 90100 foam and Dovobet® ointment in the stratum corneum.
Official Title
-----------------
Dermatopharmacokinetic Trial of LEO 90100 Foam
Conditions
-----------------
Healthy
Intervention / Treatment
-----------------
* Drug: LEO 90100 foam
* Drug: Dovobet® ointment
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Japanese male subjects, aged 20 to 40 years inclusive Exclusion Criteria: Body Mass Index outside the range 18-25 kg/m² Use of any medication (systemic or topical) within 2 weeks of Day 1.
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 40 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: A single application of LEO 90100 foam and Dovobet® ointment will be applied to multiple test sites on the innerside of both arms of trial subjects. The trial consists of 2 parts. The first part, (pilot part) will evaluate the pharmacokinetic profile of LEO 90100 foam and Dovobet® ointment by measuring the amount of each of the active ingredients in the stratum corneum and determine conditions for the second part of the trial. The second part (pivotal part) will compare the amount of each of the active ingredients at steady state or close-to-steady state between LEO 90100 foam and Dovobet® ointment. The sample size and the number of application sites in the pivotal part will be determined based on the results of the pilot part.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LEO 90100 foam<br>LEO 90100 foam (containing calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g). Pilot part: 6 single applications of LEO 90100 foam on Day 1 (for 12 sites in total). Pivotal part: To be decided based on the result of the pilot part | Drug: LEO 90100 foam<br>* A foam formulation of the active comparator Dovobet® ointment<br>|
| Active Comparator: Dovobet® ointment<br>Pilot part: 6 single applications of Dovobet® ointment on Day 1 (for 12 sites in total). Pivotal part: To be decided based on the result of the pilot part | Drug: Dovobet® ointment<br>* Ointment formulation containing same active ingredients as LEO 90100 foam<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount of each of the 2 active ingredients, calcipotriol and betamethasone dipropionate, in the stratum corneum obtained by means of tape stripping after application of LEO 90100 foam and Dovobet® ointment. | Amount (nanogram) of calcipotriol and betamethasone dipropionate in the stratum corneum will be compared between the two formulations by selected time points using an ANOVA model with treatment/formulation as systematic effect. | 2, 4, 6, 8, 12 and 24 hr after drug application. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety data - number of adverse events | Number of adverse events | up to 15 Days after drug application |
|
|||
NCT02314923
|
Placebo Controlled, Dose Response, Safety and Immunogenicity Study of Vesicular Stomatitis Virus (VSV) Ebola Vaccine in Healthy Adults (V920-004)
|
Ebola virus has infected and killed people, mostly in Africa. In 2014, the Ebola virus has affected several thousand people. There is no approved effective way to treat or prevent Ebola. Researchers are trying to develop a vaccine for it. This is a study of the anti-Ebola vaccine BPSC-1001 to see if it is safe and to see how it affects people's immune system.
|
Between 1994 and the present, there have been many Ebola viruses (EBOV) outbreaks affecting mostly central Africa. However, the 2014 West African outbreak significantly exceeds all previous outbreaks in geographic range, number of individuals affected and in disruption of typical activities of civil society.~This is a Phase 1 safety and tolerability study to evaluate a novel vaccine to Ebola using a live replicating vesicular stomatitis virus (VSV) replacing the gene encoding the G envelope glycoprotein with the gene encoding the envelope glycoprotein from the Zaire strain of Ebola (VSVΔG-ZEBOV also known as V920 and BPSC-1001).
|
A Phase 1 Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Dose-Response Study to Evaluate the Safety and Immunogenicity of the BPSC-1001 (VSVΔG-ZEBOV) Ebola Virus Vaccine Candidate in Healthy Adult Subjects
|
Ebola Virus
|
* Biological: V920 Vaccine
* Other: Placebo
|
Inclusion Criteria:~Healthy adult male or non-pregnant, non-lactating adult female, ages 18 to 60 (inclusive) at the time of screening~Have provided written informed consent prior to screening procedures~Free of clinically significant health problems, as determined by pertinent medical history, physical examination and clinical judgment of the investigator.~Available, able, and willing to participate for all study visits and procedures.~Males and females who are willing to practice abstinence from sexual intercourse with the opposite sex, or willing to use effective methods of contraception, from at least 30 days prior to vaccination until study end.~Be willing to minimize blood and body fluid exposure of others for 7 days after vaccination by:~Using effective barrier prophylaxis, such as latex condoms, during penetrative sexual intercourse~Avoiding the sharing of needles, razors, or toothbrushes~Avoiding open-mouth kissing~Resides in the geographic area of a clinical study site for 1 year after vaccination without risk of deployment outside the U.S.~Exclusion Criteria:~History of prior infection with a filovirus or prior participation in a filovirus vaccine trial~History of prior infection with VSV or receipt of a VSV vectored vaccine~Has been involved in the care in any capacity of a patient with Ebola virus infection within the previous 21 days~Is a healthcare worker who has direct contact with patients (nurse, physician, dentist, emergency medical technician, dental hygienist)~Has a house-hold contact (HHC) who is immunodeficient, on immunosuppressive medications, human immunodeficiency virus (HIV)-positive, pregnant, has an unstable medical condition~Has an HHC, or is a childcare worker who has direct contact with children, 5 years of age or younger~Direct hands-on job preparing food in the food industry~History of employment in an industry involved in contact with ruminant animals, veterinary sciences, or other potential exposure to VSV~History of employment or activity which involves potential contact with filoviruses~History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions~Known allergy to the components of the BPSC1001 vaccine product~Receipt of investigational product up to 30 days prior to randomization or ongoing participation in another clinical trial~Receipt of licensed non-live vaccines within 14 days of planned study immunization (30 days for live vaccines)~Ability to observe possible local reactions at the eligible injections sites (deltoid region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art~Acute or chronic, clinically significant psychiatric, hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, and/or laboratory screening test. This would include a known hemoglobinopathy or coagulation abnormality.~Any baseline laboratory screening test which in the opinion of the investigator, is considered clinically significant~Any serologic evidence of hepatitis B or C infection~Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV-1, HIV-2 infection, cytotoxic therapy in the previous 5 years, and/or diabetes~Any chronic or active neurologic disorder, including migraines, seizures, and epilepsy, excluding a single febrile seizure as a child~Have a known history of Guillain-Barré Syndrome~Have an active malignancy or history of metastatic or hematologic malignancy~Suspected or known alcohol and/or illicit drug abuse within the past 5 years~Moderate or severe illness and/or fever >100.4°F within 1 week prior to vaccination (can be rescheduled)~Pregnant or lactating female, or female who intends to become pregnant during the study period~Administration of IgGs and/or any blood products within the 120 days preceding study entry or planned administration during the study period~History of blood donation within 60 days of enrollment or plans to donate within the study period~Administration of chronic (defined as more than 14 days) immunosuppressants or other immune modifying drugs within 6 months of study entry~For corticosteroids, this includes prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day~Intranasal, topical, and intra-articular steroids are allowed~Unwilling to allow storage and use of blood for future vaccine research~28. Research staff or the immediate family of research staff directly involved with the clinical study.~29. Unwilling to undergo diagnostic evaluation of joint signs and symptoms, which may include arthrocentesis if clinically indicated based on presence of effusion and if the procedure is acceptable to the subject at the time (Cohort 2 only) 30. Unwilling to undergo diagnostic evaluation of skin rash, to include punch biopsy if clinically indicated and if the procedure is acceptable to the subject at the time (Cohort 2 only) 31. Research staff or the immediate family of research staff directly involved in the clinical study 32. Any other significant finding that in the opinion of the investigator would increase the risk of the individual having an adverse outcome from participating in this study 33. Elective surgery or hospitalization planned during the period of study participation 34. Has traveled to an area where the World Health Organization has declared as an Ebola outbreak zone 35. History of chronic inflammatory disease (e.g., rheumatoid arthritis, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Crohn's disease, ulcerative colitis, and gout), symptomatic osteoarthritis, or any other autoimmune or autoinflammatory disorder
|
18 Years
|
60 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study comprised two separate cohorts. Cohort 1 consisted of the 4 lower V920 dose groups (3x10^3 pfu, 3x10^4 pfu, 3x10^5 pfu, and 3x10^6 pfu). Cohort 2 consisted of the 3 higher V920 dose groups (9x10^6 pfu, 2x10^7 pfu, 1x10^8 pfu) plus a bridging group that received vaccine at the highest dose evaluated in Cohort 1 (i.e. 3x10^6 pfu). Both Cohorts 1 and 2 had a placebo group.
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With One or More Solicited Injection-site Adverse Events by Severity | An AE can be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Injection-site AEs prompted on the Vaccination Report Card (VRC) were erythema, pain, tenderness and swelling. AEs were assessed for severity by the investigator according to a toxicity grading scale based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening. The percentage of participants that experienced at least 1 solicited injection-site AE was summarized by grade. | Up to 14 days postvaccination |
| Percentage of Participants With One or More Solicited Systemic Adverse Events by Severity | An AE can be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Systemic AEs included subjective and objective fever, shivering/chills, sweats, myalgia, arthralgia, joint swelling, joint tenderness, fatigue, headache, gastrointestinal symptoms (nausea, vomiting, abdominal pain, and diarrhea), mucosal lesion, and skin lesion (including any blisters). AEs were assessed for severity by the investigator as follows: Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening. The percentage of participants that experienced at least one systemic AE was summarized by grade. | Up to 14 days postvaccination |
| Percentage of Participants With One or More Unsolicited Vaccine-related Adverse Event by Severity | An AE can be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Unsolicited vaccine-related AEs were those events not specifically listed as either an injection-site (local) or systemic in the VRC and were reported as at least possibly related to the study vaccine or placebo. The AEs were further assessed for severity by the investigator as follows: Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening. The percentage of participants that experienced at least one unsolicited vaccine-related AE was summarized by grade.. | Up to 56 days postvaccination |
| Percentage of Participants With One or More Serious Adverse Event (SAE) by Severity | An adverse event is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An SAE is an AE that results in death, is life-threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event. SAEs were assessed for severity by the investigator as follows: Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening; 5=Fatal. The percentage of participants that experienced at least 1 SAE was summarized by grade. | Up to 360 days postvaccination |
| Geometric Mean Titers (GMTs) of Zaire Ebola Virus- (ZEBOV)-Specific Immunoglobulin-G (IgG) Antibody | Blood was drawn on Day 28 to assess the GMTs of ZEBOV-specific IgG antibodies as determined by Enzyme-linked immunosorbent assay (ELISA). | 28 days postvaccination |
| Optimum Dose for General Use Prophylaxis With V920 | The optimum dose for general use prophylaxis with V920 was determined following the review of all immunogenicity and safety data. | Day 360 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Copies of Vector Ribonucleic Acid (RNA) for Participants With a V920 Polymerase Chain Reaction (PCR) Result ≥ Lower Limit of Quantification (LLOQ) | Participants had blood, assessed for evidence of V920 via polymerase chain reaction (PCR). Mean copies of RNA was reported for all participants who had reading ≥ the LLOQ (62.5 copies/mL) | Days 1, 2, 3, 4, 7, 14 and 28 post-vaccination |
| Percentage of Participants With Seroconversion for ZEBOV-specific IgG | Blood was drawn on Days 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days to assess the GMTs via ELISA. Seroconversion was defined as a post-vaccination titer ≥ 200 ELISA Units/mL that was also at least a 4-fold increase in titer compared to baseline. | 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days postvaccination |
| Percentage of Participants With Seroconversion for ZEBOV Neutralizing Antibodies | Blood was drawn on Days 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days to assess the GMTs of Zaire ebolavirus neutralizing antibodies as determined plaque reduction neutralization titer (reciprocal of the dilution that resulted in a 60% decrease in plaques) (PRNT60). | 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days postvaccination |
|
Hemorrhagic Fever, Ebola, Virus Diseases, Infections, Hemorrhagic Fevers, Viral, RNA Virus Infections, Filoviridae Infections, Mononegavirales Infections
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3x10^3 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^3 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 3x10^4 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^4 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 3x10^5 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^5 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 3x10^6 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^6 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 9x10^6 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 9x10^6 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 2x10^7 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 2x10^7 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 1x10^8 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 1x10^8 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Placebo Comparator: Placebo Cohort 1<br>Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0. | Other: Placebo<br>* 0.9% Saline<br>|
| Experimental: 3x10^6 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^3 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Placebo Comparator: Placebo Cohort 2<br>Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0. | Other: Placebo<br>* 0.9% Saline<br>|
|
Placebo Controlled, Dose Response, Safety and Immunogenicity Study of Vesicular Stomatitis Virus (VSV) Ebola Vaccine in Healthy Adults (V920-004)
Study Overview
=================
Brief Summary
-----------------
Ebola virus has infected and killed people, mostly in Africa. In 2014, the Ebola virus has affected several thousand people. There is no approved effective way to treat or prevent Ebola. Researchers are trying to develop a vaccine for it. This is a study of the anti-Ebola vaccine BPSC-1001 to see if it is safe and to see how it affects people's immune system.
Detailed Description
-----------------
Between 1994 and the present, there have been many Ebola viruses (EBOV) outbreaks affecting mostly central Africa. However, the 2014 West African outbreak significantly exceeds all previous outbreaks in geographic range, number of individuals affected and in disruption of typical activities of civil society. This is a Phase 1 safety and tolerability study to evaluate a novel vaccine to Ebola using a live replicating vesicular stomatitis virus (VSV) replacing the gene encoding the G envelope glycoprotein with the gene encoding the envelope glycoprotein from the Zaire strain of Ebola (VSVΔG-ZEBOV also known as V920 and BPSC-1001).
Official Title
-----------------
A Phase 1 Randomized, Multi-Center, Double-Blind, Placebo-Controlled, Dose-Response Study to Evaluate the Safety and Immunogenicity of the BPSC-1001 (VSVΔG-ZEBOV) Ebola Virus Vaccine Candidate in Healthy Adult Subjects
Conditions
-----------------
Ebola Virus
Intervention / Treatment
-----------------
* Biological: V920 Vaccine
* Other: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adult male or non-pregnant, non-lactating adult female, ages 18 to 60 (inclusive) at the time of screening Have provided written informed consent prior to screening procedures Free of clinically significant health problems, as determined by pertinent medical history, physical examination and clinical judgment of the investigator. Available, able, and willing to participate for all study visits and procedures. Males and females who are willing to practice abstinence from sexual intercourse with the opposite sex, or willing to use effective methods of contraception, from at least 30 days prior to vaccination until study end. Be willing to minimize blood and body fluid exposure of others for 7 days after vaccination by: Using effective barrier prophylaxis, such as latex condoms, during penetrative sexual intercourse Avoiding the sharing of needles, razors, or toothbrushes Avoiding open-mouth kissing Resides in the geographic area of a clinical study site for 1 year after vaccination without risk of deployment outside the U.S. Exclusion Criteria: History of prior infection with a filovirus or prior participation in a filovirus vaccine trial History of prior infection with VSV or receipt of a VSV vectored vaccine Has been involved in the care in any capacity of a patient with Ebola virus infection within the previous 21 days Is a healthcare worker who has direct contact with patients (nurse, physician, dentist, emergency medical technician, dental hygienist) Has a house-hold contact (HHC) who is immunodeficient, on immunosuppressive medications, human immunodeficiency virus (HIV)-positive, pregnant, has an unstable medical condition Has an HHC, or is a childcare worker who has direct contact with children, 5 years of age or younger Direct hands-on job preparing food in the food industry History of employment in an industry involved in contact with ruminant animals, veterinary sciences, or other potential exposure to VSV History of employment or activity which involves potential contact with filoviruses History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions Known allergy to the components of the BPSC1001 vaccine product Receipt of investigational product up to 30 days prior to randomization or ongoing participation in another clinical trial Receipt of licensed non-live vaccines within 14 days of planned study immunization (30 days for live vaccines) Ability to observe possible local reactions at the eligible injections sites (deltoid region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art Acute or chronic, clinically significant psychiatric, hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, and/or laboratory screening test. This would include a known hemoglobinopathy or coagulation abnormality. Any baseline laboratory screening test which in the opinion of the investigator, is considered clinically significant Any serologic evidence of hepatitis B or C infection Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV-1, HIV-2 infection, cytotoxic therapy in the previous 5 years, and/or diabetes Any chronic or active neurologic disorder, including migraines, seizures, and epilepsy, excluding a single febrile seizure as a child Have a known history of Guillain-Barré Syndrome Have an active malignancy or history of metastatic or hematologic malignancy Suspected or known alcohol and/or illicit drug abuse within the past 5 years Moderate or severe illness and/or fever >100.4°F within 1 week prior to vaccination (can be rescheduled) Pregnant or lactating female, or female who intends to become pregnant during the study period Administration of IgGs and/or any blood products within the 120 days preceding study entry or planned administration during the study period History of blood donation within 60 days of enrollment or plans to donate within the study period Administration of chronic (defined as more than 14 days) immunosuppressants or other immune modifying drugs within 6 months of study entry For corticosteroids, this includes prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day Intranasal, topical, and intra-articular steroids are allowed Unwilling to allow storage and use of blood for future vaccine research 28. Research staff or the immediate family of research staff directly involved with the clinical study. 29. Unwilling to undergo diagnostic evaluation of joint signs and symptoms, which may include arthrocentesis if clinically indicated based on presence of effusion and if the procedure is acceptable to the subject at the time (Cohort 2 only) 30. Unwilling to undergo diagnostic evaluation of skin rash, to include punch biopsy if clinically indicated and if the procedure is acceptable to the subject at the time (Cohort 2 only) 31. Research staff or the immediate family of research staff directly involved in the clinical study 32. Any other significant finding that in the opinion of the investigator would increase the risk of the individual having an adverse outcome from participating in this study 33. Elective surgery or hospitalization planned during the period of study participation 34. Has traveled to an area where the World Health Organization has declared as an Ebola outbreak zone 35. History of chronic inflammatory disease (e.g., rheumatoid arthritis, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Crohn's disease, ulcerative colitis, and gout), symptomatic osteoarthritis, or any other autoimmune or autoinflammatory disorder
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
Interventional Model Description: The study comprised two separate cohorts. Cohort 1 consisted of the 4 lower V920 dose groups (3x10^3 pfu, 3x10^4 pfu, 3x10^5 pfu, and 3x10^6 pfu). Cohort 2 consisted of the 3 higher V920 dose groups (9x10^6 pfu, 2x10^7 pfu, 1x10^8 pfu) plus a bridging group that received vaccine at the highest dose evaluated in Cohort 1 (i.e. 3x10^6 pfu). Both Cohorts 1 and 2 had a placebo group.
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3x10^3 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^3 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 3x10^4 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^4 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 3x10^5 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^5 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 3x10^6 pfu Vaccine Cohort 1<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^6 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 9x10^6 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 9x10^6 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 2x10^7 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 2x10^7 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Experimental: 1x10^8 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 1x10^8 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Placebo Comparator: Placebo Cohort 1<br>Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0. | Other: Placebo<br>* 0.9% Saline<br>|
| Experimental: 3x10^6 pfu Vaccine Cohort 2<br>Participants will receive a 1-mL intramuscular injection of V920 3x10^3 pfu in the deltoid on Day 0. | Biological: V920 Vaccine<br>* Vesicular Stomatitis Virus (VSV)-based vaccine 1-mL injection containing 3x10^3, 3x10^4, 3x10^5, 3x10^6, 9x10^6, 2x10^7, or 1x10^8 pfu.<br>* Other names: BPSC-1001;|
| Placebo Comparator: Placebo Cohort 2<br>Participants will receive a 1-mL intramuscular injection of placebo in the deltoid on Day 0. | Other: Placebo<br>* 0.9% Saline<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With One or More Solicited Injection-site Adverse Events by Severity | An AE can be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Injection-site AEs prompted on the Vaccination Report Card (VRC) were erythema, pain, tenderness and swelling. AEs were assessed for severity by the investigator according to a toxicity grading scale based on the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening. The percentage of participants that experienced at least 1 solicited injection-site AE was summarized by grade. | Up to 14 days postvaccination |
| Percentage of Participants With One or More Solicited Systemic Adverse Events by Severity | An AE can be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Systemic AEs included subjective and objective fever, shivering/chills, sweats, myalgia, arthralgia, joint swelling, joint tenderness, fatigue, headache, gastrointestinal symptoms (nausea, vomiting, abdominal pain, and diarrhea), mucosal lesion, and skin lesion (including any blisters). AEs were assessed for severity by the investigator as follows: Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening. The percentage of participants that experienced at least one systemic AE was summarized by grade. | Up to 14 days postvaccination |
| Percentage of Participants With One or More Unsolicited Vaccine-related Adverse Event by Severity | An AE can be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the study vaccine or protocol-specified procedure is also an adverse event. Unsolicited vaccine-related AEs were those events not specifically listed as either an injection-site (local) or systemic in the VRC and were reported as at least possibly related to the study vaccine or placebo. The AEs were further assessed for severity by the investigator as follows: Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening. The percentage of participants that experienced at least one unsolicited vaccine-related AE was summarized by grade.. | Up to 56 days postvaccination |
| Percentage of Participants With One or More Serious Adverse Event (SAE) by Severity | An adverse event is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An SAE is an AE that results in death, is life-threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event. SAEs were assessed for severity by the investigator as follows: Grade 1=Mild; Grade 2=Moderate; Grade 3=Severe; Grade 4=Potentially life-threatening; 5=Fatal. The percentage of participants that experienced at least 1 SAE was summarized by grade. | Up to 360 days postvaccination |
| Geometric Mean Titers (GMTs) of Zaire Ebola Virus- (ZEBOV)-Specific Immunoglobulin-G (IgG) Antibody | Blood was drawn on Day 28 to assess the GMTs of ZEBOV-specific IgG antibodies as determined by Enzyme-linked immunosorbent assay (ELISA). | 28 days postvaccination |
| Optimum Dose for General Use Prophylaxis With V920 | The optimum dose for general use prophylaxis with V920 was determined following the review of all immunogenicity and safety data. | Day 360 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Copies of Vector Ribonucleic Acid (RNA) for Participants With a V920 Polymerase Chain Reaction (PCR) Result ≥ Lower Limit of Quantification (LLOQ) | Participants had blood, assessed for evidence of V920 via polymerase chain reaction (PCR). Mean copies of RNA was reported for all participants who had reading ≥ the LLOQ (62.5 copies/mL) | Days 1, 2, 3, 4, 7, 14 and 28 post-vaccination |
| Percentage of Participants With Seroconversion for ZEBOV-specific IgG | Blood was drawn on Days 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days to assess the GMTs via ELISA. Seroconversion was defined as a post-vaccination titer ≥ 200 ELISA Units/mL that was also at least a 4-fold increase in titer compared to baseline. | 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days postvaccination |
| Percentage of Participants With Seroconversion for ZEBOV Neutralizing Antibodies | Blood was drawn on Days 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days to assess the GMTs of Zaire ebolavirus neutralizing antibodies as determined plaque reduction neutralization titer (reciprocal of the dilution that resulted in a 60% decrease in plaques) (PRNT60). | 7, 14, 28, 56, 84 (Cohort 1 only), 180, and 360 days postvaccination |
|
|
NCT03254602
|
Intense Therapeutic Ultrasound for the Treatment of Chronic Plantar Fasciitis
|
A clinical trial evaluating the effectiveness, safety and patient tolerance for the use of Intense Therapeutic Ultrasound (ITU) for chronic, Plantar Fasciitis musculoskeletal tissue pain reduction began in August 2016 and was completed in April 2017. The clinical setting: University Foot and Ankle Institute, Santa Monica, California, USA; Single-Blinded, pivotal study for chronic plantar fasciitis.
|
Intense Therapeutic Ultrasound (ITU) is an established ultrasound based therapy in which sound waves are concentrated and focused into selected musculoskeletal tissue, to produce selective thermal coagulative changes over a small controlled area while leaving the surrounding tissue unaffected. These coagulative changes are known to begin the body's tissue response cascade and promote collagen generation in the targeted anatomy resulting in pain reduction.
|
Intense Therapeutic Ultrasound for the Treatment of Chronic Plantar Fasciitis Musculoskeletal Pain Reduction
|
Plantar Fasciitis, Chronic
|
* Device: Intense Therapeutic Ultrasound Treatment
|
Inclusion Criteria:~Chronic Pain (>90 days) from previously diagnosed Plantar Fasciitis, where Standard of Care regimens failed to relief pain in the affected anatomy.~No History of surgery to the affected anatomy.~No alternative treatment procedures within the last 90 days.~Age: 18 - 85, depending on the study.~Unilateral Pain~Willingness to complete treatment and post treatment regimen as described.~Patients who have provided written and verbal informed consent.~Exclusion Criteria:~Patients currently enrolled in any other non-conservative, device, or Investigational New Drug clinical trial, or who have participated in a clinical study involving the Plantar Fascia, thirty days prior to study initiation;~Patients who have participated in any other clinical study involving an investigational product 30 days prior to enrollment that, in the opinion of the Principal Investigator, could affect the outcome of this study;~Patients who have received previous treatment in the symptomatic limb (not including conservative treatment);~At the Principal Investigator's discretion, any patient that should be excluded based on their current condition or medical history.
|
18 Years
|
85 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Reported Pain Via the Universal Visual Analog Scale: Pass Criteria = at Least 25% Pain Reduction | Patient Reported Pain Reduction meeting or exceeding 25% using the Universal Visual Analog Scale. The Universal Visual Analog Scale is a 10 Point pain scale, where 0 = No Pain, 1 = slight Pain and 10 = the patient's worst imaginable pain. Ratings of 2 to 9 describe pain increases of 10%/Rating. For this measure a reduction of 25% on the Universal Visual Analog Scale is considered meeting the Pain Reduction Criteria. Lower Scale numbers compared to reported baseline ratings equates to pain reduction. | At 12 weeks after the first treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ultrasound Changes | Diagnostic Ultrasound Changes: Hypoechoic Lesion Volume Reduction following 2 Intense Therapeutic Ultrasound Treatments | At 12 Weeks after the first treatment |
| Percentage of Change of Pain and Hypoechoic Lesion Volume Compared to Baseline | Compare percentage of Mean changes in pain via the Patient Reported Universal Visual Analog Scale compared to Mean Patient Reported Baseline Pain Scores and percentage of Mean change of Plantar Fascia Hypoechoic Lesion Volume compared to mean baseline Hypoechoic lesion volume following two Intense Therapeutic Ultrasound Treatments, using Diagnostic Ultrasound Images. For Plantar Fascia Hypoechoic Lesion Volume, each lesion volume was calculated using: (4/3) π x R1 x R2 x R3, where r = Radius of each measurement: Lesion Length(1), width(2) and depth(3) | At 12 Weeks after the first treatment |
|
Fasciitis, Fasciitis, Plantar, Musculoskeletal Diseases, Foot Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intense Therapeutic Ultrasound Treatment<br>Intense Therapeutic Ultrasound treatment applied along the length and width of the proximal Plantar Fascia. 1000 - 5 Joule pulses were applied twice, four weeks apart. | Device: Intense Therapeutic Ultrasound Treatment<br> <br> * Other names: Actisound;|
|
Intense Therapeutic Ultrasound for the Treatment of Chronic Plantar Fasciitis
Study Overview
=================
Brief Summary
-----------------
A clinical trial evaluating the effectiveness, safety and patient tolerance for the use of Intense Therapeutic Ultrasound (ITU) for chronic, Plantar Fasciitis musculoskeletal tissue pain reduction began in August 2016 and was completed in April 2017. The clinical setting: University Foot and Ankle Institute, Santa Monica, California, USA; Single-Blinded, pivotal study for chronic plantar fasciitis.
Detailed Description
-----------------
Intense Therapeutic Ultrasound (ITU) is an established ultrasound based therapy in which sound waves are concentrated and focused into selected musculoskeletal tissue, to produce selective thermal coagulative changes over a small controlled area while leaving the surrounding tissue unaffected. These coagulative changes are known to begin the body's tissue response cascade and promote collagen generation in the targeted anatomy resulting in pain reduction.
Official Title
-----------------
Intense Therapeutic Ultrasound for the Treatment of Chronic Plantar Fasciitis Musculoskeletal Pain Reduction
Conditions
-----------------
Plantar Fasciitis, Chronic
Intervention / Treatment
-----------------
* Device: Intense Therapeutic Ultrasound Treatment
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chronic Pain (>90 days) from previously diagnosed Plantar Fasciitis, where Standard of Care regimens failed to relief pain in the affected anatomy. No History of surgery to the affected anatomy. No alternative treatment procedures within the last 90 days. Age: 18 - 85, depending on the study. Unilateral Pain Willingness to complete treatment and post treatment regimen as described. Patients who have provided written and verbal informed consent. Exclusion Criteria: Patients currently enrolled in any other non-conservative, device, or Investigational New Drug clinical trial, or who have participated in a clinical study involving the Plantar Fascia, thirty days prior to study initiation; Patients who have participated in any other clinical study involving an investigational product 30 days prior to enrollment that, in the opinion of the Principal Investigator, could affect the outcome of this study; Patients who have received previous treatment in the symptomatic limb (not including conservative treatment); At the Principal Investigator's discretion, any patient that should be excluded based on their current condition or medical history.
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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intense Therapeutic Ultrasound Treatment<br>Intense Therapeutic Ultrasound treatment applied along the length and width of the proximal Plantar Fascia. 1000 - 5 Joule pulses were applied twice, four weeks apart. | Device: Intense Therapeutic Ultrasound Treatment<br> <br> * Other names: Actisound;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Reported Pain Via the Universal Visual Analog Scale: Pass Criteria = at Least 25% Pain Reduction | Patient Reported Pain Reduction meeting or exceeding 25% using the Universal Visual Analog Scale. The Universal Visual Analog Scale is a 10 Point pain scale, where 0 = No Pain, 1 = slight Pain and 10 = the patient's worst imaginable pain. Ratings of 2 to 9 describe pain increases of 10%/Rating. For this measure a reduction of 25% on the Universal Visual Analog Scale is considered meeting the Pain Reduction Criteria. Lower Scale numbers compared to reported baseline ratings equates to pain reduction. | At 12 weeks after the first treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ultrasound Changes | Diagnostic Ultrasound Changes: Hypoechoic Lesion Volume Reduction following 2 Intense Therapeutic Ultrasound Treatments | At 12 Weeks after the first treatment |
| Percentage of Change of Pain and Hypoechoic Lesion Volume Compared to Baseline | Compare percentage of Mean changes in pain via the Patient Reported Universal Visual Analog Scale compared to Mean Patient Reported Baseline Pain Scores and percentage of Mean change of Plantar Fascia Hypoechoic Lesion Volume compared to mean baseline Hypoechoic lesion volume following two Intense Therapeutic Ultrasound Treatments, using Diagnostic Ultrasound Images. For Plantar Fascia Hypoechoic Lesion Volume, each lesion volume was calculated using: (4/3) π x R1 x R2 x R3, where r = Radius of each measurement: Lesion Length(1), width(2) and depth(3) | At 12 Weeks after the first treatment |
|
|
NCT04886908
|
Comparative Retrospective Analysis of Skin Tumors of the Eyelids and Face in 2 Brussels University Hospitals Over 5 Years in Dermatology or Ophthalmology
|
Skin cancers are the most common of all cancers. Their incidence has increased sharply over the decades.This increase in incidence partly reflects an aging population and behavioral patterns such as repeated exposure to the sun. Indeed, exposure to UV rays is the predominant factor involved in the pathogenesis of these tumors, hence the fact that they mainly develop in photo-exposed regions such as the cephalic extremity.~The objective of this study is to provide an epidemiological analysis of tumors in the populations of both CHU Brugmann and St Pierre hospitals.
|
Comparative Retrospective Analysis of Skin Tumors of the Eyelids and Face in 2 Brussels University Hospitals Over 5 Years in Dermatology or Ophthalmology
|
Skin Cancer
|
* Other: Data extraction from medical files
|
Inclusion Criteria:~Final diagnosis confirmed by pathological analysis, epidemiological and clinical information available from patients.~Exclusion Criteria:~Patients who have expressed a refusal to access their medical file or incomplete data will not be taken into account.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Age | Age of the patient at the time of diagnose | 5 minutes |
| Sex | Sex of the patient | 5 minutes |
| Name of the department in which the patient is followed | Ophthalmology-CHU Brugmann hospital or Dermatology-CHU Brugmann hospital or Ophthalmology- CHU St Pierre Hospital or Dermatology-CHU St Pierre Hospital | 5 minutes |
| Tumor anatomical location | Eyelids are distributed in their different regions: internal cantus and external cantus, upper eyelid and lower eyelid. Same for the face: ears, zygomatic, forehead, temples, cheeks, nose, upper lip, lower lip, chin, nasolabial fold, preauricular area, retroauricular area, brow bone. | 5 minutes |
| Tumor size | Tumor size in millimeters | 5 minutes |
| Laterality | Laterality: left, right, median | 5 minutes |
| Multiple or single tumor | Multiple or single tumor | 5 minutes |
| Primitive tumor or recidive | Primitive tumor or recidive | 5 minutes |
| Risk factor: phototype | Phototype 1 to 6 on the Fitzpatrick scale. The Fitzpatrick scale is a numerical classification schema for human skin color. Type 1 is pale skin that always burns, never tans and type 6 is deeply pigmented dark brown to darkest brown skin that never burns. | 5 minutes |
| Risk factor: immunosuppression (yes/no) | Pathogenic or iatrogenic, history of malignant skin tumors other than melanoma, personal or family history of melanoma | 5 minutes |
| Risk factor: keratosis | Actinic keratosis of the face | 5 minutes |
| Risk factor: solar exposition (yes/no) | Lived in a sunny European country> 1 year, lived in a sunny country outside Europe> 1 year, sunbed use> 1 session, history of solar erythema during childhood. | 5 minutes |
| Diagnosis | Time between the appearance of the tumor and the first consultation | 5 minutes |
| Locoregional extension report (yes/no) | Locoregional extension report (yes/no) | 5 minutes |
| Histological diagnosis of the tumor | Histological diagnosis of the tumor | 5 minutes |
| Healthy or invaded margins | Healthy or invaded margins | 5 minutes |
| Superficial or infiltrating tumor | Superficial or infiltrating tumor | 5 minutes |
| Diagnostic method | Diagnostic method: curettage, punch, biopsy, flattening | 5 minutes |
| Surgical management method | Biopsy resection, plasty, graft, second-line healing, enucleation, additional treatment: radiotherapy, immunotherapy, liquid nitrogen | 5 minutes |
|
Skin Neoplasms, Eyelid Neoplasms, Neoplasms by Site, Neoplasms, Skin Diseases, Facial Neoplasms, Head and Neck Neoplasms, Eye Neoplasms, Eye Diseases, Eyelid Diseases
|
| Intervention/Treatment |
| --- |
|Other: Data extraction from medical files|Data extraction from medical files|
|
Comparative Retrospective Analysis of Skin Tumors of the Eyelids and Face in 2 Brussels University Hospitals Over 5 Years in Dermatology or Ophthalmology
Study Overview
=================
Brief Summary
-----------------
Skin cancers are the most common of all cancers. Their incidence has increased sharply over the decades.This increase in incidence partly reflects an aging population and behavioral patterns such as repeated exposure to the sun. Indeed, exposure to UV rays is the predominant factor involved in the pathogenesis of these tumors, hence the fact that they mainly develop in photo-exposed regions such as the cephalic extremity. The objective of this study is to provide an epidemiological analysis of tumors in the populations of both CHU Brugmann and St Pierre hospitals.
Official Title
-----------------
Comparative Retrospective Analysis of Skin Tumors of the Eyelids and Face in 2 Brussels University Hospitals Over 5 Years in Dermatology or Ophthalmology
Conditions
-----------------
Skin Cancer
Intervention / Treatment
-----------------
* Other: Data extraction from medical files
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Final diagnosis confirmed by pathological analysis, epidemiological and clinical information available from patients. Exclusion Criteria: Patients who have expressed a refusal to access their medical file or incomplete data will not be taken into account.
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: Data extraction from medical files|Data extraction from medical files|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Age | Age of the patient at the time of diagnose | 5 minutes |
| Sex | Sex of the patient | 5 minutes |
| Name of the department in which the patient is followed | Ophthalmology-CHU Brugmann hospital or Dermatology-CHU Brugmann hospital or Ophthalmology- CHU St Pierre Hospital or Dermatology-CHU St Pierre Hospital | 5 minutes |
| Tumor anatomical location | Eyelids are distributed in their different regions: internal cantus and external cantus, upper eyelid and lower eyelid. Same for the face: ears, zygomatic, forehead, temples, cheeks, nose, upper lip, lower lip, chin, nasolabial fold, preauricular area, retroauricular area, brow bone. | 5 minutes |
| Tumor size | Tumor size in millimeters | 5 minutes |
| Laterality | Laterality: left, right, median | 5 minutes |
| Multiple or single tumor | Multiple or single tumor | 5 minutes |
| Primitive tumor or recidive | Primitive tumor or recidive | 5 minutes |
| Risk factor: phototype | Phototype 1 to 6 on the Fitzpatrick scale. The Fitzpatrick scale is a numerical classification schema for human skin color. Type 1 is pale skin that always burns, never tans and type 6 is deeply pigmented dark brown to darkest brown skin that never burns. | 5 minutes |
| Risk factor: immunosuppression (yes/no) | Pathogenic or iatrogenic, history of malignant skin tumors other than melanoma, personal or family history of melanoma | 5 minutes |
| Risk factor: keratosis | Actinic keratosis of the face | 5 minutes |
| Risk factor: solar exposition (yes/no) | Lived in a sunny European country> 1 year, lived in a sunny country outside Europe> 1 year, sunbed use> 1 session, history of solar erythema during childhood. | 5 minutes |
| Diagnosis | Time between the appearance of the tumor and the first consultation | 5 minutes |
| Locoregional extension report (yes/no) | Locoregional extension report (yes/no) | 5 minutes |
| Histological diagnosis of the tumor | Histological diagnosis of the tumor | 5 minutes |
| Healthy or invaded margins | Healthy or invaded margins | 5 minutes |
| Superficial or infiltrating tumor | Superficial or infiltrating tumor | 5 minutes |
| Diagnostic method | Diagnostic method: curettage, punch, biopsy, flattening | 5 minutes |
| Surgical management method | Biopsy resection, plasty, graft, second-line healing, enucleation, additional treatment: radiotherapy, immunotherapy, liquid nitrogen | 5 minutes |
|
||||
NCT03829397
|
To Investigate the Correlation of Stroke Patients and Demoralized
|
This study aim to clarify the participants's mental state with Demoralization Scale- Mandarin Version(DS-MV). Based on clinical observations and literature review, investigators assume participants's DS-MV score high correlation with PHQ-9 score.
|
The Chinese version of Demoralization Scale-Mandarin Version (DS-MV) was used to assess the mental state of patients with stroke after debridement. The statistical analysis test of correlation is carried out, and the reliability and validity test and the norm establishment of the Chinese version are further tested. Convenient sampling will be performed at a single medical facility. The planned implementation period is 2019/01/01 ~ 2019/12/31, and the location of the case is the rehabilitation ward and outpatient clinic of Taoyuan Hospital. The diagnosis must be: intensive stroke or hemorrhagic brain within three years. In the case of a 20- to 100-year-old clinical patient with stroke, the subject should explain the content of the case, and the subject will complete the test consent form after informed consent, and then begin the evaluation process of the self-assessment questionnaire. The assessment procedure is preceded by a clinical psychologist conducting with MMSE test to determine the cognitive function. When the patient's consciousness is blurred, the simple intelligent state test (MMSE) score less than 24 points, aphasia can not be effectively communicated, the diagnosis of mental illness or mental disorder has been recorded on the medical record, or the patient or family member is unwilling to sign the informed consent form. If the above situation is met, subjects will be excluded. The self-assessment questionnaire will obtain the scores of the subjects in the Chinese version of the Demoralization Scale-Mandarin Version (DS-MV) and the Patient Health Questionnaire (PHQ-9). Statistical analysis, as well as the Chinese version of the loss of the scale of the reliability and validity of the test and the establishment of clinical norm scores.
|
To Investigate the Correlation of Stroke Patients and Demoralized
|
Post-stroke Depression
|
* Diagnostic Test: Questionnaire
|
Inclusion Criteria:~Inpatient and outpatient of rehabilitation department in Taoyuan General Hospital, patients diagnosis : who have an infarct stroke or hemorrhagic stroke within three years.~Exclusion Criteria:~Conscious state confusion, the MMSE score less than 24.~Unable to understand information, speech disorders, dementia, aphasia.~The diagnosis of mental illness or mental disorder has been recorded on the medical history.~The patient or family unwilling to sign an informed consent.
|
20 Years
|
100 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| demoralization Scale-Mandarin Version (DS-MV) total score | When participants was included, investigators get on one-time assessment use the demoralization Scale-Mandarin Version (DS-MV). The demoralization Scale-Mandarin Version (DS-MV) minimum score are 0, and maximum score are 96, cut-off point are 30. No subscale. | through study completion, an average of 1 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| demoralization Scale-Mandarin Version (DS-MV) total score split-half reliability | Divide the demoralization Scale-Mandarin Version (DS-MV) into half, and then test the items of the previous half (item 1-12) and the second half (item 13-24) of the questionnaire. Then the two half questionnaire scores were test of correlation coefficient.Then If the degree of correlation is high, the reliability is very high. | through study completion, an average of 1 year |
| Patient Health Questionnaire (PHQ-9) total score | When participants was included, investigators get on one-time assessment use the Patient Health Questionnaire (PHQ-9) .Patient Health Questionnaire (PHQ-9) minimum score are 0, and maximum score are 27. No subscale. | through study completion, an average of 1 year |
| demoralization Scale-Mandarin Version (DS-MV) total score criterion-related validity | Correlation test between demoralization Scale-Mandarin Version (DS-MV) total score and Patient Health Questionnaire(PHQ-9) total score. | through study completion, an average of 1 year |
|
Demoralization Scale-Mandarin Version, Demoralization syndrome
|
Nervous System Diseases, Stroke, Brain Diseases, Central Nervous System Diseases, Cerebrovascular Disorders, Vascular Diseases, Cardiovascular Diseases
|
| Intervention/Treatment |
| --- |
|Diagnostic Test: Questionnaire|Questionnaire|
|
To Investigate the Correlation of Stroke Patients and Demoralized
Study Overview
=================
Brief Summary
-----------------
This study aim to clarify the participants's mental state with Demoralization Scale- Mandarin Version(DS-MV). Based on clinical observations and literature review, investigators assume participants's DS-MV score high correlation with PHQ-9 score.
Detailed Description
-----------------
The Chinese version of Demoralization Scale-Mandarin Version (DS-MV) was used to assess the mental state of patients with stroke after debridement. The statistical analysis test of correlation is carried out, and the reliability and validity test and the norm establishment of the Chinese version are further tested. Convenient sampling will be performed at a single medical facility. The planned implementation period is 2019/01/01 2019/12/31, and the location of the case is the rehabilitation ward and outpatient clinic of Taoyuan Hospital. The diagnosis must be: intensive stroke or hemorrhagic brain within three years. In the case of a 20- to 100-year-old clinical patient with stroke, the subject should explain the content of the case, and the subject will complete the test consent form after informed consent, and then begin the evaluation process of the self-assessment questionnaire. The assessment procedure is preceded by a clinical psychologist conducting with MMSE test to determine the cognitive function. When the patient's consciousness is blurred, the simple intelligent state test (MMSE) score less than 24 points, aphasia can not be effectively communicated, the diagnosis of mental illness or mental disorder has been recorded on the medical record, or the patient or family member is unwilling to sign the informed consent form. If the above situation is met, subjects will be excluded. The self-assessment questionnaire will obtain the scores of the subjects in the Chinese version of the Demoralization Scale-Mandarin Version (DS-MV) and the Patient Health Questionnaire (PHQ-9). Statistical analysis, as well as the Chinese version of the loss of the scale of the reliability and validity of the test and the establishment of clinical norm scores.
Official Title
-----------------
To Investigate the Correlation of Stroke Patients and Demoralized
Conditions
-----------------
Post-stroke Depression
Intervention / Treatment
-----------------
* Diagnostic Test: Questionnaire
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inpatient and outpatient of rehabilitation department in Taoyuan General Hospital, patients diagnosis : who have an infarct stroke or hemorrhagic stroke within three years. Exclusion Criteria: Conscious state confusion, the MMSE score less than 24. Unable to understand information, speech disorders, dementia, aphasia. The diagnosis of mental illness or mental disorder has been recorded on the medical history. The patient or family unwilling to sign an informed consent.
Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 100 Years
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Diagnostic Test: Questionnaire|Questionnaire|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| demoralization Scale-Mandarin Version (DS-MV) total score | When participants was included, investigators get on one-time assessment use the demoralization Scale-Mandarin Version (DS-MV). The demoralization Scale-Mandarin Version (DS-MV) minimum score are 0, and maximum score are 96, cut-off point are 30. No subscale. | through study completion, an average of 1 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| demoralization Scale-Mandarin Version (DS-MV) total score split-half reliability | Divide the demoralization Scale-Mandarin Version (DS-MV) into half, and then test the items of the previous half (item 1-12) and the second half (item 13-24) of the questionnaire. Then the two half questionnaire scores were test of correlation coefficient.Then If the degree of correlation is high, the reliability is very high. | through study completion, an average of 1 year |
| Patient Health Questionnaire (PHQ-9) total score | When participants was included, investigators get on one-time assessment use the Patient Health Questionnaire (PHQ-9) .Patient Health Questionnaire (PHQ-9) minimum score are 0, and maximum score are 27. No subscale. | through study completion, an average of 1 year |
| demoralization Scale-Mandarin Version (DS-MV) total score criterion-related validity | Correlation test between demoralization Scale-Mandarin Version (DS-MV) total score and Patient Health Questionnaire(PHQ-9) total score. | through study completion, an average of 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Demoralization Scale-Mandarin Version, Demoralization syndrome
|
|
NCT03482063
|
The Effects of 12 Weeks Supplementation With a B-vitamin and Herbal Supplement on Neurocognitive Function and Mood
|
The aim of the present study is to evaluate chronic supplementation with Swisse Ultiboost Memory + Focus over a 12 week period on memory in individuals with optimal and sub-optimal nutrient profiles.
|
This study will have two co-primary outcomes; one each to measure memory and focus. Short term memory will be measured by the spatial working memory task from the Swinburne University Computerised Cognitive Assessment Battery. Focus will be measured by the incongruent version of the stroop colour-word task from the Swinburne University Computerised Cognitive Assessment Battery. Through investigations of blood vitamin markers, biomarkers of inflammation and neuroimaging techniques, this study aims to provide insight to the mechanisms through which the supplement is acting.~This study is a phase II clinical trial, which will follow a randomised, placebo-controlled, double-blind, parallel groups design. One hundred and forty participants will complete a 12 week intervention, which will involve three testing visits to Swinburne University, as well as in-home mood assessments. Of these, 60 participants will also complete an MRI component. Participants will be randomly allocated to one of two groups; one receiving active supplementation of Swisse Ultiboost Memory + Focus, and the other receiving a placebo formulation.~Prior to participants being enrolled in the study a telephone screening interview will be completed, to reduce the likelihood of ineligible participants attending study visits. Eligible participants will complete three study visits; a Screening and Practice visit (V0), Baseline Visit (V1), and the Final Visit (V2). The participant's baseline visit (V1) will be scheduled within two weeks of their screening and practice visit (V0). The participant's final visit (V2) will be scheduled 12 weeks (± 3 days) from the baseline visit (V1). Therefore, it is anticipated that participation in the trial will last a maximum of 14 weeks.~For the 12 week supplementation period between their baseline (V1) and final (V2) visits, participants will be instructed to consume one tablet, twice a day, of either Swisse Ultiboost Memory + Focus or placebo, with a meal. Participants will be requested to abstain from the treatment on the day of their final visit.~Participants will also be required to complete online mood assessments in their home, twice a week for the duration of the 12 week supplementation period. Two laboratory assessment points will be measured, at baseline (V1) and at the final visit (V2). Twenty four in-home assessment points will be measured, twice a week during participation in the study.
|
The Effects of 12 Weeks Supplementation With a B-vitamin and Herbal Supplement on Neurocognitive Function and Mood: The Memory + Focus Clinical Trial (MAST - Memory and Attention Supplement Trial)
|
Neurocognitive Function, Mood
|
* Dietary Supplement: Swisse Ultiboost Memory + Focus
* Other: Placebo
|
Inclusion Criteria:~Healthy males and females aged between 40 and 65 years~Non-smokers~English speaking~Not currently being treated for anxiety, depression or psychiatric disorders (if treatment was >2 years ago, can include)~Not suffering from cognitive impairment~No history of or currently suffering from neurological conditions (Epilepsy, Parkinsons, stroke, serious head trauma), cardiac diseases or diabetes requiring medication~Not taking any medication, herbal extracts, vitamin supplements or illicit drugs which might reasonably be expected to interfere with cognition or mood for 4 weeks prior to (and duration of) study, as defined by the exclusion list (Appendix 9)~No health conditions that would affect absorption of food, including the following: food allergies, impaired kidney function , liver disease (Hepatitis C, cirrhosis) and/or gastrointestinal diseases (e.g. Inflammatory bowel disease (Ulcerative Colitis, Crohn's Disease), coeliac disease, peptic ulcers)~Right handed (MRI component only)~Not hypertensive (systolic < 160 mm Hg and/or diastolic < 100 mm Hg at rest)~Not misusing substances~Have internet access in the home~Normal or corrected vision and normal colour vision~Not currently participating, or has not participated in another study investigating a nutraceutical supplement within the past 4 weeks~Not currently pregnant or lactating (for female participants of child bearing potential, the use of effective contraceptive method(s) for birth control for the duration of the study)~Willing and able to provide written informed consent.~Understands and is willing and able to comply with all study procedures.~Exclusion Criteria:~Chronic health condition~Smoker~Non-English speaking~Treatment for anxiety, depression (Becks Depression Inventory score ≥20 to be confirmed at screening visit) or other psychiatric conditions within the past 2 years~Suffering from cognitive impairment, dementia, Alzheimer's disease and/or a score of <24 on the Mini-Mental State Examination (to be confirmed at screening visit)~Neurological conditions (Epilepsy, Parkinsons, stroke, serious head trauma), cardiac diseases or diabetes requiring medication~Use of concomitant medications and/or vitamin supplements that could have cognitive or mood effects in the 4 weeks preceding the baseline visit, as defined by the exclusion list (Appendix 9)~Health conditions that would affect absorption of food, including the following: food allergies, impaired kidney function, liver disease (Hepatitis C, cirrhosis) and/or gastrointestinal diseases (e.g. Inflammatory bowel disease (Ulcerative Colitis, Crohn's Disease), coeliac disease, peptic ulcers)~Left handed (MRI participants only)~Blood pressure consistent with uncontrolled hypertension, (systolic > 160 mm Hg and/or diastolic > 100 mm Hg at rest)~Alcohol or substance abuse. Alcohol abuse is defined as >14 drinks per week.~Hypersensitivity to the investigational product or any of the active/inactive ingredients~Currently taking Warfarin~Currently participating, or has participated in another study investigating a nutraceutical supplement within the past 4 weeks~People with metal implants, pacemaker or aneurism clip (MRI participants only)~Currently pregnant or lactating~Any condition which may interfere with the subject's ability to perform assessments (e.g. claustrophobia for the MRI arm, dyslexia, colour blindness)
|
40 Years
|
65 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, placebo-controlled, double-blind, parallel groups design
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in short term memory, as measured by the spatial working memory task from the Swinburne University Computerised Cognitive Assessment Battery. | In each trial participants are presented with a 4x4 white grid on a black background, with six grid positions containing white squares. Participants are given 3 seconds to remember where the white squares are located. The grid became blank and a series of four white squares were sequentially displayed in various grid positions for 2-seconds each. Participants responded with a yes/no response to indicate whether each square matched a position that was originally filled. In total, participants complete 14 trials, each of which are separated by a blank screen displayed for 2-seconds. Each trial was set such that two out of the four locations in the response series corresponded to the original grid locations, and two did not. The task requires participants to hold spatial information in working memory. | 12 weeks |
| Changes in focus, as measured by the incongruent version of the stroop colour-word task from the Swinburne University Computerised Cognitive Assessment Battery | The test consists of congruent and incongruent trials blocks. Stimulus words are randomly presented (RED, BLUE, GREEN, YELLOW), printed in colours either congruent or incongruent with the written word. Participants are asked to respond by pressing one of four buttons corresponding to the colour of the print while ignoring the written word. The tasks are participant-paced, meaning that as soon as a participant responds to a word, they are presented with the next word. The incongruent trial will be used as a measure of selective attention as participants are required to selectively attend to the print colour of the written word, while inhibiting the automatic reading of the written word | 12 weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simple reaction time component of the Swinburne University Computerised Cognitive Aging Battery (SUCCAB) | Participants respond with a right button press to the appearance of a single white square at the centre of the screen. Thirty targets are presented with a randomized inter-stimulus interval (ISI) to avoid anticipation effects. | 12 weeks |
| Choice reaction time component of the Swinburne University Computerised Cognitive Battery (SUCCAB) | Participants respond with a left (blue) or right (red) button press to the appearance of a blue triangle or red square respectively. Presentation order and ISI are randomized to avoid anticipation effects. | 12 weeks |
| Immediate/Delayed Recognition component of the Swinburne University Computerised Cognitive Battery (SUCCAB) | Participants are asked to study a series of 40 abstract images presented serially in the centre of the screen for 3-seconds each with no ISI. On completion, another series of images are presented, half of which were from the studied series and half that are new (Immediate condition). Participants indicate with a right (yes) or left (no) button press whether or not they recognized the image from the studied series. This task is repeated at the end of the testing session with the remaining 20 images from the studied series and another 20 new images (Delayed condition). | 12 weeks |
| Stroop Colour-Word component of the Swinburne University Computerised Cognitive Battery (SUCCAB) | he test consists of two congruent and two incongruent trials, presented alternately. Stimulus words are randomly presented (RED, BLUE, GREEN, YELLOW) in either congruent or incongruent colours for 1.7-seconds, with an ISI of 0.5-seconds. Participants responded by pressing one of four buttons corresponding to the colour of the word, irrespective of what the word read. This task is used as a measure of executive function and more specifically inhibition; participants have to inhibit the automatic reading response. | 12 weeks |
| Contextual memory component of the Swinburne University Computerised Cognitive Battery (SUCCAB) | A series of 20 everyday images are presented at the top/bottom/left/right of the screen for 3-seconds each with no ISI. On completion of the series the same images are displayed again in randomized order in the centre of the screen for 2-seconds each with no ISI. Participantsrespond with a top/bottom/left/right button press to indicate the original location of each image. The task requires participants to recall the spatial context of the original presentation and was used as a measure of episodic memory. | 12 weeks |
| Serial Threes Subtraction component of the Cognitive Demand Battery | The participant is required to count backwards in threes from a random starting number between 800 and 999. The starting number is presented on the computer screen, and then is cleared by the first response. Participants are instructed to respond as quickly and as accurately as possible using computer keyboard keys. The participant completes the task over a period of two minutes. | 12 weeks |
| Serial Sevens Subtraction component of the Cognitive Demand Battery | The participant is required to count backwards in sevens from a random starting number between 800 and 999. The starting number is presented on the computer screen, and then is cleared by the first response. Participants are instructed to respond as quickly and as accurately as possible using computer keyboard keys. The participant completes the task over a period of two minutes. | 12 weeks |
| Rapid Visual Information Processing component of the Cognitive Demand Battery | A series of digits are presented in the centre of the screen at the rate of 100 per minute. The participant is required to detect three consecutive ascending odd or three consecutive ascending even digits. The participant responds to the detection of a target string by pressing the 'space bar'. The task is continuous for five minutes, with eight target strings presented each minute. This task is used as a measure of processing speed. | 12 weeks |
| Perceived Stress Scale (PSS) | The PSS measures the extent to which respondents have perceived events in their life as stressful over the last month. There are 14 items, each scored on a 5-point scale ranging from 'never' to 'very often'. Seven of these items are positively stated items, and therefore they are reverse scored. Higher scores on the PSS are associated with higher levels of perceived stress. | 12 weeks |
| Profile of Mood States (PROMS) | The POMS requires participants to indicate the degree to which they have identified with 65 mood-related adjectives over the past week. Each item is on a 5-point scale from 'not at all' to 'extremely'. Items are summed into six factors; Tensio n-Anxiety, Confusion-Bewilderment, Anger-Hostilit y, Depressio n-Dejection, Fatigue-Inertia and Vigor-Activit y.A Total Mood Disturbance (TMD) score is computed as the sum of the first 5 factors minus Vigor-Activity. High scores indicate greater mood disturbance on all scales except Vigor-Activity. | 12 weeks |
| The Depression, Anxiety and Stress Scale (DASS) | The DASS measures comprises of 21 items that pertain to affect- related symptoms for three sub-factors: depression, anxiety and stress. Participants must respond to each item to reflect their experiences over the past week. Each item is on a 4-point scale fro m 0 to 3, with a total range of scores from 0 to 63. Higher scores indicate a higher degree of dysfunction and less desirable affect experience. A score of zero does not indicate positive mood, but rather the lack of presence of negative mood state symptoms. The DASS is considered relevant for both clinical and non-clinical populations as some experience of such symptoms is considered normal in day to day life. | 12 weeks |
| State-Trait Anxiety Inventory - State Subscale (STAI-S) | The State-Trait Anxiety Inventory (STAI) contains two subscales; one that measures the transient experiences of anxiety (STAI-S) and the other measures the more stable personality characteristic (STAI-T). The state subscale (STAI-S) contains 20 items, asking participants about to respond with how they are feeling 'right now', ranging from 'not at all' to 'very much so'. The total range of scores is from 20 to 80, with higher scores indicating higher levels of anxiety. | 12 weeks |
| Bond-Lader Visual Analogue Scales (VAS) | This task comprises of 16 100mm lines anchored at either end by antonyms. Participants must mark their current subjective state between the antonyms on each line, bearing in mind that each end of the scale represents an extreme. Each line is scored as millimetres to the mark from the negative antonym. From the scores, a factor analysis can isolate three factors; 'alertness', 'calmness' and 'contentedness'. Scores for each factor represent the unweighted average number of millimetres from the negative antonym for the individual scales contributing to the factor. | 12 weeks |
| Stress, Anxiety, Mental Fatigue, Concentration and Mental Stamina Visual Analogue Mood Scales (VAMS) | The following scales will ask the participant to rate their subjective experiences of stress, fatigue, concentration and stamina in the present moment. In each case, participants will rate their subjective feeling on a 100mm visual analogue scale, and be required to mark the line as a response to reflect their current subjective state: Stress, anxiety, mental fatigue, concentration, mental stamina. | 12 weeks |
| Prospective and Retrospective Memory Questionnaire (PRMQ) | The PRMQ is a self-rated measure of prospective and retrospective memory slips in everyday life. It consists of sixteen statements, half which relate to prospective memory failures, and the other half relate to retrospective failures. The participant must respond with how often each statement applies to them. Items are scored in a likert format with response options from 'very often' to 'never'. | 12 weeks |
| Chalder Fatigue Scale (CFS) | The CFS is a self-rated measure of fatigue severity over the past week. The scale consists of 14 items, eight relating to physical symptoms and six questions relating to mental fat igue. Items are scored in a likert format with response options ranging from 'better than usual' to 'much worse than usual'. | 12 weeks |
| Subjective Experience Survey | At the end of the study, participants will be asked the following qualitative questions: 1.While taking part in this study, have you experienced any positive changes in your physical or mental health (mood, stress, brain function) that you don't know the cause of or you think may be caused by the study tablets? 2.While taking part in this study, have you experienced any negative changes in your physical or mental health (mood, stress, brain function) that you don't know the cause of or you think may be caused by the study tablets? 3.While taking part in this study have you experienced any unusual changes (not necessarily good or bad) in your physical or mental health (mood, stress, brain function) that you don't know the cause of or you think may be caused by the study tablets? These questions are designed to capture any additional changes to cognition or mood that may not be picked up using the other questionnaires. | 12 weeks |
| Biomedical measures | Participants will have fasting blood samples taken at the participant's baseline (V1) visit and their final (V2) visit. Blood samples will be collected by a qualified venepuncture technician or research nurse at the Centre for Human Psychopharmacology and securely stored in a freezer. All blood samples (with the exception of blood for essential fatty acid panel analysis) will sent to an Australian Clinical Labs pathology lab in Melbourne to be analysed. Samples used for essential fatty acid panel analysis will be sent to the University of Adelaide pathology lab to be analysed.~Samples will be tested for: Vitamin B1, B2, B6, B12, Red Cell Folate and Homocysteine, high-sensitivity C-reactive protein, electrolytes, renal function, liver function and cholesterol.~A medical investigator will assess the clinical significance of any abnormal values. | 12 weeks |
| Neuroimaging | Participants who are consented for additional neuroimaging will undergo the following: functional magnetic resonance imaging, arterial spin labelling and diffusion tensor imaging. | 12 weeks |
|
B vitamin, herbal supplement, attention
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Swisse Ultiboost Memory + Focus<br>two tablets daily, one tablet during or immediately after breakfast, and one tablet during or immediately after lunch, for the duration of the trial period | Dietary Supplement: Swisse Ultiboost Memory + Focus<br>* B vitamins help energy release, help with metabolism of food into energy, assist energy production and vitality.~Vitamin B5 helps support normal mental performance. Brahmi, Ginkgo, Vitamin B12 and B3 help support brain function. Ginkgo helps maintain healthy circulation and delivery of oxygenated blood to the brain.~Brahmi supports memory function and recall. Vitamin B5, B6 are important for adrenal function, assist adrenal glands during stress periods.~Vitamin B2, B3, B5, B6, B12 help relieve tiredness and fatigue.<br>|
| Placebo Comparator: Placebo<br>two tablets daily, one tablet during or immediately after breakfast, and one tablet during or immediately after lunch, for the duration of the trial period | Other: Placebo<br>* riboflavin (2.2mg)<br>|
|
The Effects of 12 Weeks Supplementation With a B-vitamin and Herbal Supplement on Neurocognitive Function and Mood
Study Overview
=================
Brief Summary
-----------------
The aim of the present study is to evaluate chronic supplementation with Swisse Ultiboost Memory + Focus over a 12 week period on memory in individuals with optimal and sub-optimal nutrient profiles.
Detailed Description
-----------------
This study will have two co-primary outcomes; one each to measure memory and focus. Short term memory will be measured by the spatial working memory task from the Swinburne University Computerised Cognitive Assessment Battery. Focus will be measured by the incongruent version of the stroop colour-word task from the Swinburne University Computerised Cognitive Assessment Battery. Through investigations of blood vitamin markers, biomarkers of inflammation and neuroimaging techniques, this study aims to provide insight to the mechanisms through which the supplement is acting. This study is a phase II clinical trial, which will follow a randomised, placebo-controlled, double-blind, parallel groups design. One hundred and forty participants will complete a 12 week intervention, which will involve three testing visits to Swinburne University, as well as in-home mood assessments. Of these, 60 participants will also complete an MRI component. Participants will be randomly allocated to one of two groups; one receiving active supplementation of Swisse Ultiboost Memory + Focus, and the other receiving a placebo formulation. Prior to participants being enrolled in the study a telephone screening interview will be completed, to reduce the likelihood of ineligible participants attending study visits. Eligible participants will complete three study visits; a Screening and Practice visit (V0), Baseline Visit (V1), and the Final Visit (V2). The participant's baseline visit (V1) will be scheduled within two weeks of their screening and practice visit (V0). The participant's final visit (V2) will be scheduled 12 weeks (± 3 days) from the baseline visit (V1). Therefore, it is anticipated that participation in the trial will last a maximum of 14 weeks. For the 12 week supplementation period between their baseline (V1) and final (V2) visits, participants will be instructed to consume one tablet, twice a day, of either Swisse Ultiboost Memory + Focus or placebo, with a meal. Participants will be requested to abstain from the treatment on the day of their final visit. Participants will also be required to complete online mood assessments in their home, twice a week for the duration of the 12 week supplementation period. Two laboratory assessment points will be measured, at baseline (V1) and at the final visit (V2). Twenty four in-home assessment points will be measured, twice a week during participation in the study.
Official Title
-----------------
The Effects of 12 Weeks Supplementation With a B-vitamin and Herbal Supplement on Neurocognitive Function and Mood: The Memory + Focus Clinical Trial (MAST - Memory and Attention Supplement Trial)
Conditions
-----------------
Neurocognitive Function, Mood
Intervention / Treatment
-----------------
* Dietary Supplement: Swisse Ultiboost Memory + Focus
* Other: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males and females aged between 40 and 65 years Non-smokers English speaking Not currently being treated for anxiety, depression or psychiatric disorders (if treatment was >2 years ago, can include) Not suffering from cognitive impairment No history of or currently suffering from neurological conditions (Epilepsy, Parkinsons, stroke, serious head trauma), cardiac diseases or diabetes requiring medication Not taking any medication, herbal extracts, vitamin supplements or illicit drugs which might reasonably be expected to interfere with cognition or mood for 4 weeks prior to (and duration of) study, as defined by the exclusion list (Appendix 9) No health conditions that would affect absorption of food, including the following: food allergies, impaired kidney function , liver disease (Hepatitis C, cirrhosis) and/or gastrointestinal diseases (e.g. Inflammatory bowel disease (Ulcerative Colitis, Crohn's Disease), coeliac disease, peptic ulcers) Right handed (MRI component only) Not hypertensive (systolic < 160 mm Hg and/or diastolic < 100 mm Hg at rest) Not misusing substances Have internet access in the home Normal or corrected vision and normal colour vision Not currently participating, or has not participated in another study investigating a nutraceutical supplement within the past 4 weeks Not currently pregnant or lactating (for female participants of child bearing potential, the use of effective contraceptive method(s) for birth control for the duration of the study) Willing and able to provide written informed consent. Understands and is willing and able to comply with all study procedures. Exclusion Criteria: Chronic health condition Smoker Non-English speaking Treatment for anxiety, depression (Becks Depression Inventory score ≥20 to be confirmed at screening visit) or other psychiatric conditions within the past 2 years Suffering from cognitive impairment, dementia, Alzheimer's disease and/or a score of <24 on the Mini-Mental State Examination (to be confirmed at screening visit) Neurological conditions (Epilepsy, Parkinsons, stroke, serious head trauma), cardiac diseases or diabetes requiring medication Use of concomitant medications and/or vitamin supplements that could have cognitive or mood effects in the 4 weeks preceding the baseline visit, as defined by the exclusion list (Appendix 9) Health conditions that would affect absorption of food, including the following: food allergies, impaired kidney function, liver disease (Hepatitis C, cirrhosis) and/or gastrointestinal diseases (e.g. Inflammatory bowel disease (Ulcerative Colitis, Crohn's Disease), coeliac disease, peptic ulcers) Left handed (MRI participants only) Blood pressure consistent with uncontrolled hypertension, (systolic > 160 mm Hg and/or diastolic > 100 mm Hg at rest) Alcohol or substance abuse. Alcohol abuse is defined as >14 drinks per week. Hypersensitivity to the investigational product or any of the active/inactive ingredients Currently taking Warfarin Currently participating, or has participated in another study investigating a nutraceutical supplement within the past 4 weeks People with metal implants, pacemaker or aneurism clip (MRI participants only) Currently pregnant or lactating Any condition which may interfere with the subject's ability to perform assessments (e.g. claustrophobia for the MRI arm, dyslexia, colour blindness)
Ages Eligible for Study
-----------------
Minimum Age: 40 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, placebo-controlled, double-blind, parallel groups design
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Swisse Ultiboost Memory + Focus<br>two tablets daily, one tablet during or immediately after breakfast, and one tablet during or immediately after lunch, for the duration of the trial period | Dietary Supplement: Swisse Ultiboost Memory + Focus<br>* B vitamins help energy release, help with metabolism of food into energy, assist energy production and vitality. Vitamin B5 helps support normal mental performance. Brahmi, Ginkgo, Vitamin B12 and B3 help support brain function. Ginkgo helps maintain healthy circulation and delivery of oxygenated blood to the brain. Brahmi supports memory function and recall. Vitamin B5, B6 are important for adrenal function, assist adrenal glands during stress periods. Vitamin B2, B3, B5, B6, B12 help relieve tiredness and fatigue.<br>|
| Placebo Comparator: Placebo<br>two tablets daily, one tablet during or immediately after breakfast, and one tablet during or immediately after lunch, for the duration of the trial period | Other: Placebo<br>* riboflavin (2.2mg)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in short term memory, as measured by the spatial working memory task from the Swinburne University Computerised Cognitive Assessment Battery. | In each trial participants are presented with a 4x4 white grid on a black background, with six grid positions containing white squares. Participants are given 3 seconds to remember where the white squares are located. The grid became blank and a series of four white squares were sequentially displayed in various grid positions for 2-seconds each. Participants responded with a yes/no response to indicate whether each square matched a position that was originally filled. In total, participants complete 14 trials, each of which are separated by a blank screen displayed for 2-seconds. Each trial was set such that two out of the four locations in the response series corresponded to the original grid locations, and two did not. The task requires participants to hold spatial information in working memory. | 12 weeks |
| Changes in focus, as measured by the incongruent version of the stroop colour-word task from the Swinburne University Computerised Cognitive Assessment Battery | The test consists of congruent and incongruent trials blocks. Stimulus words are randomly presented (RED, BLUE, GREEN, YELLOW), printed in colours either congruent or incongruent with the written word. Participants are asked to respond by pressing one of four buttons corresponding to the colour of the print while ignoring the written word. The tasks are participant-paced, meaning that as soon as a participant responds to a word, they are presented with the next word. The incongruent trial will be used as a measure of selective attention as participants are required to selectively attend to the print colour of the written word, while inhibiting the automatic reading of the written word | 12 weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simple reaction time component of the Swinburne University Computerised Cognitive Aging Battery (SUCCAB) | Participants respond with a right button press to the appearance of a single white square at the centre of the screen. Thirty targets are presented with a randomized inter-stimulus interval (ISI) to avoid anticipation effects. | 12 weeks |
| Choice reaction time component of the Swinburne University Computerised Cognitive Battery (SUCCAB) | Participants respond with a left (blue) or right (red) button press to the appearance of a blue triangle or red square respectively. Presentation order and ISI are randomized to avoid anticipation effects. | 12 weeks |
| Immediate/Delayed Recognition component of the Swinburne University Computerised Cognitive Battery (SUCCAB) | Participants are asked to study a series of 40 abstract images presented serially in the centre of the screen for 3-seconds each with no ISI. On completion, another series of images are presented, half of which were from the studied series and half that are new (Immediate condition). Participants indicate with a right (yes) or left (no) button press whether or not they recognized the image from the studied series. This task is repeated at the end of the testing session with the remaining 20 images from the studied series and another 20 new images (Delayed condition). | 12 weeks |
| Stroop Colour-Word component of the Swinburne University Computerised Cognitive Battery (SUCCAB) | he test consists of two congruent and two incongruent trials, presented alternately. Stimulus words are randomly presented (RED, BLUE, GREEN, YELLOW) in either congruent or incongruent colours for 1.7-seconds, with an ISI of 0.5-seconds. Participants responded by pressing one of four buttons corresponding to the colour of the word, irrespective of what the word read. This task is used as a measure of executive function and more specifically inhibition; participants have to inhibit the automatic reading response. | 12 weeks |
| Contextual memory component of the Swinburne University Computerised Cognitive Battery (SUCCAB) | A series of 20 everyday images are presented at the top/bottom/left/right of the screen for 3-seconds each with no ISI. On completion of the series the same images are displayed again in randomized order in the centre of the screen for 2-seconds each with no ISI. Participantsrespond with a top/bottom/left/right button press to indicate the original location of each image. The task requires participants to recall the spatial context of the original presentation and was used as a measure of episodic memory. | 12 weeks |
| Serial Threes Subtraction component of the Cognitive Demand Battery | The participant is required to count backwards in threes from a random starting number between 800 and 999. The starting number is presented on the computer screen, and then is cleared by the first response. Participants are instructed to respond as quickly and as accurately as possible using computer keyboard keys. The participant completes the task over a period of two minutes. | 12 weeks |
| Serial Sevens Subtraction component of the Cognitive Demand Battery | The participant is required to count backwards in sevens from a random starting number between 800 and 999. The starting number is presented on the computer screen, and then is cleared by the first response. Participants are instructed to respond as quickly and as accurately as possible using computer keyboard keys. The participant completes the task over a period of two minutes. | 12 weeks |
| Rapid Visual Information Processing component of the Cognitive Demand Battery | A series of digits are presented in the centre of the screen at the rate of 100 per minute. The participant is required to detect three consecutive ascending odd or three consecutive ascending even digits. The participant responds to the detection of a target string by pressing the 'space bar'. The task is continuous for five minutes, with eight target strings presented each minute. This task is used as a measure of processing speed. | 12 weeks |
| Perceived Stress Scale (PSS) | The PSS measures the extent to which respondents have perceived events in their life as stressful over the last month. There are 14 items, each scored on a 5-point scale ranging from 'never' to 'very often'. Seven of these items are positively stated items, and therefore they are reverse scored. Higher scores on the PSS are associated with higher levels of perceived stress. | 12 weeks |
| Profile of Mood States (PROMS) | The POMS requires participants to indicate the degree to which they have identified with 65 mood-related adjectives over the past week. Each item is on a 5-point scale from 'not at all' to 'extremely'. Items are summed into six factors; Tensio n-Anxiety, Confusion-Bewilderment, Anger-Hostilit y, Depressio n-Dejection, Fatigue-Inertia and Vigor-Activit y.A Total Mood Disturbance (TMD) score is computed as the sum of the first 5 factors minus Vigor-Activity. High scores indicate greater mood disturbance on all scales except Vigor-Activity. | 12 weeks |
| The Depression, Anxiety and Stress Scale (DASS) | The DASS measures comprises of 21 items that pertain to affect- related symptoms for three sub-factors: depression, anxiety and stress. Participants must respond to each item to reflect their experiences over the past week. Each item is on a 4-point scale fro m 0 to 3, with a total range of scores from 0 to 63. Higher scores indicate a higher degree of dysfunction and less desirable affect experience. A score of zero does not indicate positive mood, but rather the lack of presence of negative mood state symptoms. The DASS is considered relevant for both clinical and non-clinical populations as some experience of such symptoms is considered normal in day to day life. | 12 weeks |
| State-Trait Anxiety Inventory - State Subscale (STAI-S) | The State-Trait Anxiety Inventory (STAI) contains two subscales; one that measures the transient experiences of anxiety (STAI-S) and the other measures the more stable personality characteristic (STAI-T). The state subscale (STAI-S) contains 20 items, asking participants about to respond with how they are feeling 'right now', ranging from 'not at all' to 'very much so'. The total range of scores is from 20 to 80, with higher scores indicating higher levels of anxiety. | 12 weeks |
| Bond-Lader Visual Analogue Scales (VAS) | This task comprises of 16 100mm lines anchored at either end by antonyms. Participants must mark their current subjective state between the antonyms on each line, bearing in mind that each end of the scale represents an extreme. Each line is scored as millimetres to the mark from the negative antonym. From the scores, a factor analysis can isolate three factors; 'alertness', 'calmness' and 'contentedness'. Scores for each factor represent the unweighted average number of millimetres from the negative antonym for the individual scales contributing to the factor. | 12 weeks |
| Stress, Anxiety, Mental Fatigue, Concentration and Mental Stamina Visual Analogue Mood Scales (VAMS) | The following scales will ask the participant to rate their subjective experiences of stress, fatigue, concentration and stamina in the present moment. In each case, participants will rate their subjective feeling on a 100mm visual analogue scale, and be required to mark the line as a response to reflect their current subjective state: Stress, anxiety, mental fatigue, concentration, mental stamina. | 12 weeks |
| Prospective and Retrospective Memory Questionnaire (PRMQ) | The PRMQ is a self-rated measure of prospective and retrospective memory slips in everyday life. It consists of sixteen statements, half which relate to prospective memory failures, and the other half relate to retrospective failures. The participant must respond with how often each statement applies to them. Items are scored in a likert format with response options from 'very often' to 'never'. | 12 weeks |
| Chalder Fatigue Scale (CFS) | The CFS is a self-rated measure of fatigue severity over the past week. The scale consists of 14 items, eight relating to physical symptoms and six questions relating to mental fat igue. Items are scored in a likert format with response options ranging from 'better than usual' to 'much worse than usual'. | 12 weeks |
| Subjective Experience Survey | At the end of the study, participants will be asked the following qualitative questions: 1.While taking part in this study, have you experienced any positive changes in your physical or mental health (mood, stress, brain function) that you don't know the cause of or you think may be caused by the study tablets? 2.While taking part in this study, have you experienced any negative changes in your physical or mental health (mood, stress, brain function) that you don't know the cause of or you think may be caused by the study tablets? 3.While taking part in this study have you experienced any unusual changes (not necessarily good or bad) in your physical or mental health (mood, stress, brain function) that you don't know the cause of or you think may be caused by the study tablets? These questions are designed to capture any additional changes to cognition or mood that may not be picked up using the other questionnaires. | 12 weeks |
| Biomedical measures | Participants will have fasting blood samples taken at the participant's baseline (V1) visit and their final (V2) visit. Blood samples will be collected by a qualified venepuncture technician or research nurse at the Centre for Human Psychopharmacology and securely stored in a freezer. All blood samples (with the exception of blood for essential fatty acid panel analysis) will sent to an Australian Clinical Labs pathology lab in Melbourne to be analysed. Samples used for essential fatty acid panel analysis will be sent to the University of Adelaide pathology lab to be analysed. Samples will be tested for: Vitamin B1, B2, B6, B12, Red Cell Folate and Homocysteine, high-sensitivity C-reactive protein, electrolytes, renal function, liver function and cholesterol. A medical investigator will assess the clinical significance of any abnormal values. | 12 weeks |
| Neuroimaging | Participants who are consented for additional neuroimaging will undergo the following: functional magnetic resonance imaging, arterial spin labelling and diffusion tensor imaging. | 12 weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
B vitamin, herbal supplement, attention
|
|
NCT03219112
|
Training Balance Control in Children With Cerebral Palsy Using Virtual Reality Games
|
In this study the clinical relevance of the use of commercially available virtual reality games in the rehabilitation of balance will be assessed in children with cerebral palsy. It will be investigated how different commercially available platforms (i.e. Xbox One + Kinect and Nintendo Wii + balance board) will affect the compensations of children with cerebral palsy to preserve their balance. The effect of 1 training session will be assessed as well as the effect of a long-term training of 8 weeks.
|
Training Balance Control Using Virtual Reality Games in Children With Cerebral Palsy and Typically Developing Children
|
Cerebral Palsy, Spastic
|
* Other: Balance rehabilitation using X-box One & Kinect
|
Inclusion Criteria:~children diagnosed with cerebral palsy (spastic type)~age: 8-11 years and 11 months~bilateral CP (diplegia) & unilateral CP (hemiplegia)~GMFCS level 1 & 2~able to independently stand still for 2 minutes~sufficient cooperation to participate in the measurements and training~Exclusion Criteria:~No informed consent~surgery of the lower limbs that affects mobility~Botulinum-toxin A treatment within 6 months prior to inclusion in the study~vestibular deficits, benign vertigo, ADHD or instable epilepsia~For typically developing children:~Inclusion criteria;~age: 8-11 years and 11 months~no history of neurologic, musculoskeletal or other impairments that could affect mobility
|
8 Years
|
12 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pediatric Balance Scale compared to baseline | Clinical balance scale with 14 items such as standing unsupported for 30 sec. | measured at baseline, after 40 minutes (of training), and after 8 weeks of training |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bruininks-Oseretsky test for motor proficiency - subscale 'balance' and 'speed & agility' compared to baseline | Subscales of a clinical balance scale | measured at baseline, after 40 minutes (of training), and after 8 weeks of training |
| Change in Upper body kinematics compared to baseline | Trunk and arm movements measured using 3d movement registration | measured at baseline, after 40 minutes (of training), and after 8 weeks of training |
| Change in Posturography compared to baseline | Measurements on a moveable force-platform including the limits of stability during standing | measured at baseline, after 40 minutes (of training), and after 8 weeks of training |
|
balance, rehabilitation, exergaming, virtual reality
|
Cerebral Palsy, Nervous System Diseases, Brain Damage, Chronic, Brain Diseases, Central Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>15 cp children + 10 typically developing children (anticipated) Will have 8 weeks VR training Will have 1 VR training session | Other: Balance rehabilitation using X-box One & Kinect<br>* the virtual reality games (Kinect sports rivals) can be controlled with movements of the body that are registered through the kinect camera.<br>|
| No Intervention: Control<br>15 cp children (anticipated) Will not have 8 weeks of VR training Will not have 1 VR training session | |
|
Training Balance Control in Children With Cerebral Palsy Using Virtual Reality Games
Study Overview
=================
Brief Summary
-----------------
In this study the clinical relevance of the use of commercially available virtual reality games in the rehabilitation of balance will be assessed in children with cerebral palsy. It will be investigated how different commercially available platforms (i.e. Xbox One + Kinect and Nintendo Wii + balance board) will affect the compensations of children with cerebral palsy to preserve their balance. The effect of 1 training session will be assessed as well as the effect of a long-term training of 8 weeks.
Official Title
-----------------
Training Balance Control Using Virtual Reality Games in Children With Cerebral Palsy and Typically Developing Children
Conditions
-----------------
Cerebral Palsy, Spastic
Intervention / Treatment
-----------------
* Other: Balance rehabilitation using X-box One & Kinect
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: children diagnosed with cerebral palsy (spastic type) age: 8-11 years and 11 months bilateral CP (diplegia) & unilateral CP (hemiplegia) GMFCS level 1 & 2 able to independently stand still for 2 minutes sufficient cooperation to participate in the measurements and training Exclusion Criteria: No informed consent surgery of the lower limbs that affects mobility Botulinum-toxin A treatment within 6 months prior to inclusion in the study vestibular deficits, benign vertigo, ADHD or instable epilepsia For typically developing children: Inclusion criteria; age: 8-11 years and 11 months no history of neurologic, musculoskeletal or other impairments that could affect mobility
Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 12 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: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>15 cp children + 10 typically developing children (anticipated) Will have 8 weeks VR training Will have 1 VR training session | Other: Balance rehabilitation using X-box One & Kinect<br>* the virtual reality games (Kinect sports rivals) can be controlled with movements of the body that are registered through the kinect camera.<br>|
| No Intervention: Control<br>15 cp children (anticipated) Will not have 8 weeks of VR training Will not have 1 VR training session | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pediatric Balance Scale compared to baseline | Clinical balance scale with 14 items such as standing unsupported for 30 sec. | measured at baseline, after 40 minutes (of training), and after 8 weeks of training |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bruininks-Oseretsky test for motor proficiency - subscale 'balance' and 'speed & agility' compared to baseline | Subscales of a clinical balance scale | measured at baseline, after 40 minutes (of training), and after 8 weeks of training |
| Change in Upper body kinematics compared to baseline | Trunk and arm movements measured using 3d movement registration | measured at baseline, after 40 minutes (of training), and after 8 weeks of training |
| Change in Posturography compared to baseline | Measurements on a moveable force-platform including the limits of stability during standing | measured at baseline, after 40 minutes (of training), and after 8 weeks of training |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
balance, rehabilitation, exergaming, virtual reality
|
|
NCT05126459
|
A Comparison of Oral Sedation-related Events of Three Multiagent Oral Sedation Regimens in Pediatric Dental Patients
|
This study will compare the post sedation events from three different multi-drug oral sedation regimens in order to help pediatric dentists determine the best course of action for their patients and prepare parents appropriately and caution them about the expected effects. Patients will be evaluated for adverse effects within two time periods at 8 and 24 hours post oral sedation procedure using surveys.
|
A Comparison of Oral Sedation-related Events of Three Multiagent Oral Sedation Regimens in Pediatric Dental Patients
|
Anxiety, Dental, Dental Decay
|
* Combination Product: Regimen 1
* Combination Product: Regimen #2
* Combination Product: Regimen #3
|
Inclusion Criteria:~Patients scheduled to undergo oral sedation appointments in Loma Linda University Pediatric dental clinic for operative procedures.~Age 3-6 years, Healthy ( ASA-1 )~No gender, race or ethnic restrictions.~Reason for conscious oral sedation is situational anxiety in the dental operatory~Exclusion Criteria:~Children with a history of acute illness~History upper respiratory tract infection within two weeks of treatment~Children taking any medication within the two weeks prior to scheduled dental treatment~Sedation within the last six months~Body mass index (BMI) greater than the 95th percentile for their age and sex~Failing to drink the entire amount of sedation medications dispensed
|
3 Years
|
6 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Sedation-Related Events in Regimen #1 | Compare the incidence of adverse sedation related events (categories: amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) between three different multi-agent oral sedation regimens in LLUSD pediatric dental patients who were scheduled for oral sedation.~Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty-four) hours (Survey 3) after discharge. | Change between 8 (eight) hours post oral sedation medication administration and discharge and 24 (twenty-four) hours post oral sedation medication administration and discharge. |
| Incidence of Adverse Sedation-Related Events in Regimen #2 | Compare the incidence of adverse sedation related events (categories: amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) between three different multi-agent oral sedation regimens in LLUSD pediatric dental patients who were scheduled for oral sedation.~Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty-four) hours (Survey 3) after discharge. | Change between 8 (eight) hours post oral sedation medication administration and discharge and 24 (twenty-four) hours post oral sedation medication administration and discharge. |
| Incidence of Adverse Sedation-Related Events in Regimen #3 | Compare the incidence of adverse sedation related events (categories: amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) between three different multi-agent oral sedation regimens in LLUSD pediatric dental patients who were scheduled for oral sedation.~Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty-four) hours (Survey 3) after discharge. | Change between 8 (eight) hours post oral sedation medication administration and discharge and 24 (twenty-four) hours post oral sedation medication administration and discharge. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare incidence of adverse effect related to the use of three medications versus two medications | Compare the number and type of adverse effect related (Amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) to the use of three medications versus two medications.~Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty four) hours (Survey 3) after discharge | 24 (twenty-four) hours post oral sedation medication administration (composite measurement) |
|
Pediatric, Dental
|
Dental Caries, Tooth Demineralization, Tooth Diseases, Stomatognathic Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Regimen 1<br>Oral administration - Hydroxyzine (1.5 - 2mg/kg) Oral administration - Meperidine (1.5 -2 mg/kg) Oral administration - Midazolam (0.5- 0.75 mg/kg) Inhalation - Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) | Combination Product: Regimen 1<br>* Administer orally after informed consent obtained prior to any dental procedure. Hydroxyzine (1.5- 2mg/kg) + Meperidine (1.5 -2 mg/kg) + Midazolam (0.5- 0.75 mg/kg) In combination with oral drugs stated above, administeration via inhalation of Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) via inhalation.<br>|
| Experimental: Regimen 2<br>Oral administration - Hydroxyzine (1.5 - 2mg/kg) Oral administration- Meperidine (1.5 -2 mg/kg) Inhalation - Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) - | Combination Product: Regimen #2<br>* Administer orally after informed consent obtained prior to any dental procedure. Hydroxyzine (1.5 - 2mg/kg) + Meperidine (1.5 -2 mg/kg). Administer Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) via inhalation.<br>|
| Experimental: Regimen 3<br>Oral administration - Hydroxyzine (1.5 - 2mg/kg) Oral administration - Midazolam (0.5- 0.75 mg/kg) Inhalation- Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) | Combination Product: Regimen #3<br>* Administer orally after informed consent obtained prior to any dental procedure. Hydroxyzine (1.5 - 2mg/kg) + Midazolam (0.5- 0.75 mg/kg). Administer Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) via inhalation.<br>|
|
A Comparison of Oral Sedation-related Events of Three Multiagent Oral Sedation Regimens in Pediatric Dental Patients
Study Overview
=================
Brief Summary
-----------------
This study will compare the post sedation events from three different multi-drug oral sedation regimens in order to help pediatric dentists determine the best course of action for their patients and prepare parents appropriately and caution them about the expected effects. Patients will be evaluated for adverse effects within two time periods at 8 and 24 hours post oral sedation procedure using surveys.
Official Title
-----------------
A Comparison of Oral Sedation-related Events of Three Multiagent Oral Sedation Regimens in Pediatric Dental Patients
Conditions
-----------------
Anxiety, Dental, Dental Decay
Intervention / Treatment
-----------------
* Combination Product: Regimen 1
* Combination Product: Regimen #2
* Combination Product: Regimen #3
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients scheduled to undergo oral sedation appointments in Loma Linda University Pediatric dental clinic for operative procedures. Age 3-6 years, Healthy ( ASA-1 ) No gender, race or ethnic restrictions. Reason for conscious oral sedation is situational anxiety in the dental operatory Exclusion Criteria: Children with a history of acute illness History upper respiratory tract infection within two weeks of treatment Children taking any medication within the two weeks prior to scheduled dental treatment Sedation within the last six months Body mass index (BMI) greater than the 95th percentile for their age and sex Failing to drink the entire amount of sedation medications dispensed
Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 6 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: Regimen 1<br>Oral administration - Hydroxyzine (1.5 - 2mg/kg) Oral administration - Meperidine (1.5 -2 mg/kg) Oral administration - Midazolam (0.5- 0.75 mg/kg) Inhalation - Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) | Combination Product: Regimen 1<br>* Administer orally after informed consent obtained prior to any dental procedure. Hydroxyzine (1.5- 2mg/kg) + Meperidine (1.5 -2 mg/kg) + Midazolam (0.5- 0.75 mg/kg) In combination with oral drugs stated above, administeration via inhalation of Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) via inhalation.<br>|
| Experimental: Regimen 2<br>Oral administration - Hydroxyzine (1.5 - 2mg/kg) Oral administration- Meperidine (1.5 -2 mg/kg) Inhalation - Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) - | Combination Product: Regimen #2<br>* Administer orally after informed consent obtained prior to any dental procedure. Hydroxyzine (1.5 - 2mg/kg) + Meperidine (1.5 -2 mg/kg). Administer Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) via inhalation.<br>|
| Experimental: Regimen 3<br>Oral administration - Hydroxyzine (1.5 - 2mg/kg) Oral administration - Midazolam (0.5- 0.75 mg/kg) Inhalation- Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) | Combination Product: Regimen #3<br>* Administer orally after informed consent obtained prior to any dental procedure. Hydroxyzine (1.5 - 2mg/kg) + Midazolam (0.5- 0.75 mg/kg). Administer Nitrous oxide/oxygen (30-50% N2O/ 70-50% O2) via inhalation.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Sedation-Related Events in Regimen #1 | Compare the incidence of adverse sedation related events (categories: amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) between three different multi-agent oral sedation regimens in LLUSD pediatric dental patients who were scheduled for oral sedation. Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty-four) hours (Survey 3) after discharge. | Change between 8 (eight) hours post oral sedation medication administration and discharge and 24 (twenty-four) hours post oral sedation medication administration and discharge. |
| Incidence of Adverse Sedation-Related Events in Regimen #2 | Compare the incidence of adverse sedation related events (categories: amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) between three different multi-agent oral sedation regimens in LLUSD pediatric dental patients who were scheduled for oral sedation. Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty-four) hours (Survey 3) after discharge. | Change between 8 (eight) hours post oral sedation medication administration and discharge and 24 (twenty-four) hours post oral sedation medication administration and discharge. |
| Incidence of Adverse Sedation-Related Events in Regimen #3 | Compare the incidence of adverse sedation related events (categories: amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) between three different multi-agent oral sedation regimens in LLUSD pediatric dental patients who were scheduled for oral sedation. Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty-four) hours (Survey 3) after discharge. | Change between 8 (eight) hours post oral sedation medication administration and discharge and 24 (twenty-four) hours post oral sedation medication administration and discharge. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare incidence of adverse effect related to the use of three medications versus two medications | Compare the number and type of adverse effect related (Amount and frequency of sleeping, level of activity, gastrointestinal discomfort, central nervous system, respiratory depression, paradoxical reactions) to the use of three medications versus two medications. Data will be collected in the form of 3 survey sets: the surveys is survey set 1 are written surveys to be completed by the dentist (Survey 1), and survey sets 2&3 are phone surveys to be conducted by the researcher with the parents 8 (eight) hours (Survey 2) and 24 (twenty four) hours (Survey 3) after discharge | 24 (twenty-four) hours post oral sedation medication administration (composite measurement) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pediatric, Dental
|
|
NCT01291394
|
To Assess the Level of Adherence of Subjects Receiving SAIZEN® Via Easypod™ in France
|
This is a National, Multicentre, Observational Registry to study adherence and long term outcomes of therapy in paediatric subjects using Easypod™ electromechanical device for growth hormone treatment from hospitals in France and to assess the level of adherence of subjects receiving SAIZEN® via Easypod™.
|
Subjects will be enrolled in this observational, multi-center study to assess adherence and treatment outcomes. Parents will provide their written agreement to upload their child's data in the study electronic CRF.~Easypod™ is an electromechanical device that delivers growth hormone and also records injections' date and time. Adherence data will be primarily derived from injections recorded in the Easypod™ device combined with physician data entry of outcome measures (i.e. height & weight). This will allow the establishment of adherence profiles and evaluate the link with subsequent clinical outcomes.~Since this is an observational study, there will be no study-specific clinical interventions and subjects will be treated according to the clinical and laboratory findings as routinely evaluated by the physician. Auxological and laboratory data will be reported prospectively throughout the duration of the study. At baseline, available data can be recorded retrospectively from the subjects' medical file and Easypod™ device Data will be collected retrospectively and prospectively. This will allow the establishment of adherence profiles and subsequent clinical outcomes. Collected data will be also analyzed in a multinational pooled analysis of comparable national studies.~Primary Objective:~• To assess the level of adherence of subjects receiving Saizen® via Easypod™~Secondary Objectives:~To describe the impact of adherence on clinical outcomes for subject receiving Saizen® via Easypod™~To identify adherence subject profiling~To asses the Impact of adherence on insulin-like growth factor-1 (IGF1) ranges/levels
|
Easypod Connect: A National, Multicentre, Observational Registry to Study Adherence and Long Term Outcomes of Therapy in Paediatric Subjects Using Easypod™ Electromechanical Device for Growth Hormone Treatment
|
Growth Disorders
|
* Device: Easypod™
|
Inclusion Criteria:~Administered Saizen® via the Easypod™ electromechanical device according to pediatric registered indications (Growth Hormone Deficiency, Small for Gestational Age, Turner-Syndrome or prepubertal children with Chronic Renal Failure).~Naïve subjects or already treated with Saizen and Easypod for maximum 1 year~Male and Female between 2 - 18 years of age, or over 18 without fusion of growth plates~Parent's or guardian's (or subject if over 18 without fusion of growth plates) written agreement, given before entering data into the study, with the understanding that the subject or parent/guardian may withdraw agreement at any time without prejudice to future medical care.~Exclusion Criteria:~Subjects taking Saizen® in whom growth plates have fused (i.e. taking growth hormone for it's metabolic effects)~Contra-indications to Saizen® as defined in the French Summary of Product Characteristics (SmPC)~Use of an investigational drug or participation in an interventional clinical study
|
2 Years
|
18 Years
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean percent of recorded adherence | | At least 6 months and up to 5 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of adherence and growth outcome (change in height velocity (HV), change in HV-Standard Deviation Score (HV-SDS), change in height-Standard Deviation Score) after each year of Saizen® treatment with Easypod™ | | At least 6 months and up to 5 years |
| Subject adherence profile | Subject adherence profile based on age, gender, indication, self-injection or not, time on treatment, administration regimen (6 or 7 days/ week), combination of pituitary hormone deficiencies, previous and/or concomitant treatments, socio-economic data | At least 6 months and up to 5 years |
| Correlation of adherence with IGF-1 levels/ranges | | At least 6 months and up to 5 years |
|
Growth disorders, Saizen, Easypod, Growth hormone, Pediatric subject
|
Growth Disorders, Pathologic Processes
|
| Intervention/Treatment |
| --- |
|Device: Easypod™|Saizen (Somatotropin) as per Summary of Product Characteristics administered by Easypod™|
|
To Assess the Level of Adherence of Subjects Receiving SAIZEN® Via Easypod™ in France
Study Overview
=================
Brief Summary
-----------------
This is a National, Multicentre, Observational Registry to study adherence and long term outcomes of therapy in paediatric subjects using Easypod™ electromechanical device for growth hormone treatment from hospitals in France and to assess the level of adherence of subjects receiving SAIZEN® via Easypod™.
Detailed Description
-----------------
Subjects will be enrolled in this observational, multi-center study to assess adherence and treatment outcomes. Parents will provide their written agreement to upload their child's data in the study electronic CRF. Easypod™ is an electromechanical device that delivers growth hormone and also records injections' date and time. Adherence data will be primarily derived from injections recorded in the Easypod™ device combined with physician data entry of outcome measures (i.e. height & weight). This will allow the establishment of adherence profiles and evaluate the link with subsequent clinical outcomes. Since this is an observational study, there will be no study-specific clinical interventions and subjects will be treated according to the clinical and laboratory findings as routinely evaluated by the physician. Auxological and laboratory data will be reported prospectively throughout the duration of the study. At baseline, available data can be recorded retrospectively from the subjects' medical file and Easypod™ device Data will be collected retrospectively and prospectively. This will allow the establishment of adherence profiles and subsequent clinical outcomes. Collected data will be also analyzed in a multinational pooled analysis of comparable national studies. Primary Objective: • To assess the level of adherence of subjects receiving Saizen® via Easypod™ Secondary Objectives: To describe the impact of adherence on clinical outcomes for subject receiving Saizen® via Easypod™ To identify adherence subject profiling To asses the Impact of adherence on insulin-like growth factor-1 (IGF1) ranges/levels
Official Title
-----------------
Easypod Connect: A National, Multicentre, Observational Registry to Study Adherence and Long Term Outcomes of Therapy in Paediatric Subjects Using Easypod™ Electromechanical Device for Growth Hormone Treatment
Conditions
-----------------
Growth Disorders
Intervention / Treatment
-----------------
* Device: Easypod™
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Administered Saizen® via the Easypod™ electromechanical device according to pediatric registered indications (Growth Hormone Deficiency, Small for Gestational Age, Turner-Syndrome or prepubertal children with Chronic Renal Failure). Naïve subjects or already treated with Saizen and Easypod for maximum 1 year Male and Female between 2 - 18 years of age, or over 18 without fusion of growth plates Parent's or guardian's (or subject if over 18 without fusion of growth plates) written agreement, given before entering data into the study, with the understanding that the subject or parent/guardian may withdraw agreement at any time without prejudice to future medical care. Exclusion Criteria: Subjects taking Saizen® in whom growth plates have fused (i.e. taking growth hormone for it's metabolic effects) Contra-indications to Saizen® as defined in the French Summary of Product Characteristics (SmPC) Use of an investigational drug or participation in an interventional clinical study
Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum 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: Easypod™|Saizen (Somatotropin) as per Summary of Product Characteristics administered by Easypod™|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean percent of recorded adherence | | At least 6 months and up to 5 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of adherence and growth outcome (change in height velocity (HV), change in HV-Standard Deviation Score (HV-SDS), change in height-Standard Deviation Score) after each year of Saizen® treatment with Easypod™ | | At least 6 months and up to 5 years |
| Subject adherence profile | Subject adherence profile based on age, gender, indication, self-injection or not, time on treatment, administration regimen (6 or 7 days/ week), combination of pituitary hormone deficiencies, previous and/or concomitant treatments, socio-economic data | At least 6 months and up to 5 years |
| Correlation of adherence with IGF-1 levels/ranges | | At least 6 months and up to 5 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Growth disorders, Saizen, Easypod, Growth hormone, Pediatric subject
|
|
NCT04016779
|
Evaluation of SPN-812 (Viloxazine Extended-release Capsule) in Adults With ADHD
|
This study will evaluate the efficacy and safety of SPN-812 (Viloxazine extended-release capsules; 200-600 mg) in adults 18-65 years of age with Attention-Deficit/Hyperactivity Disorder (ADHD).
|
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, 2-arm, parallel-group, flexible dose trial assessing the efficacy and safety of SPN-812 (Viloxazine extended-release capsules; 200-600 mg) as monotherapy for the treatment of adults 18-65 years old with Attention-Deficit/Hyperactivity Disorder (ADHD).
|
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Flexible-Dose Study of the Efficacy and Safety of SPN-812 in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)
|
Attention-Deficit/Hyperactivity Disorder (ADHD)
|
* Drug: Placebo
* Drug: SPN-812
|
Inclusion Criteria:~Is male or female, aged 18 to ≤ 65 years at screening.~Is able to read and understand the Informed Consent Form (ICF).~Written informed consent obtained from the subject (a signed ICF).~Weight within the normal or overweight ranges according to accepted values of the Body Mass Index Chart (18.0 to 35 kg/m2).~Is able to swallow capsules whole, without crushing, chewing or cutting.~Is willing and able to attend study appointments within the specified time windows.~Has a primary diagnosis of ADHD according to the DSM-5 classification, with diagnosis made at least 6 months prior to screening and confirmed with Structured Clinical Interview for DSM-5 Clinical Trials version (SCID-5-CT).~Has an AISRS Adult ADHD (Attention-Deficit/Hyperactivity Disorder) Investigator Symptom Rating Scale total score of ≥ 26 at the Screening Visit and at the Baseline Visit (V2, Day 1).~Has a CGI-S score of ≥ 4 (moderately ill or worse) at the Screening Visit (V1) and Baseline Visit (V2, Day 1).~Females of childbearing potential (FOCP) must be either sexually inactive (abstinent) or, if sexually active, must agree to use one of the following acceptable birth control methods beginning 30 days prior to the first dose of SM and throughout the study:~Simultaneous use of male condom and intra-uterine contraceptive device placed at least 4 weeks prior to first SM administration~Surgically sterile male partner~Simultaneous use of male condom and diaphragm with spermicide~Established hormonal contraceptive~Females are considered not to be of childbearing potential if they are either post-menopausal (amenorrhea for at least 2 years and serum follicle stimulating hormone (FSH) level of >40 IU/L) or permanently sterilized (e.g., bilateral tubal ligation, hysterectomy, bilateral oophorectomy for 6 months minimum prior to screening).~Males must:~Use 2 methods of contraception in combination if his female partner is of childbearing potential; this combination of contraceptive methods must be used from the Baseline Visit to ≥ 1 month after the last dose of SM, or~Have been surgically sterilized prior to the Screening Visit.~Exclusion Criteria:~Has previously enrolled in a SPN-812 study.~Is currently participating in another clinical trial or has participated in a clinical trial within 60 days prior to the first Screening Visit.~Is a member of the study personnel or of their immediate families, or is a subordinate (or immediate family member of a subordinate) to any of the study personnel.~Female subjects who are pregnant, lactating and/or sexually active and not agreeing to use one of the acceptable birth control methods throughout the study.~Has history of severe drug allergy or hypersensitivity, or known hypersensitivity, to the study medication or excipients.~Has history of moderate or severe head trauma or other neurological disorder or systemic medical disease that, in the Investigator's opinion, is likely to affect central nervous system functioning. This would include subjects with:~A current diagnosis of a major neurological disorder; or~Seizures, seizure disorder or seizure-like events; or a history of seizure disorder within the immediate family (siblings, parents); or~Encephalopathy~Has any history of schizophrenia, schizoaffective disorder, bipolar disorder, borderline personality disorder, antisocial personality disorder, narcissistic personality disorder, autism, post-traumatic stress disorder or obsessive-compulsive disorder.~Has any current psychiatric disorder (per DSM-5 criteria) other than ADHD with the following exceptions: ADHD is primary diagnosis with comorbidity/secondary diagnoses of major depression disorder (MDD), nicotine dependence, social anxiety disorder, generalized anxiety disorder, or phobias, and subject is not receiving pharmacological treatment for the comorbidity/secondary diagnoses (e.g., antidepressant for MDD) at time of screening nor for the duration of study.~Has a Symptoms of Depression Questionnaire (SDQ) mean score >3.0 at screening.~Has a Hamilton Anxiety Rating Scale (HAM-A) score of > 21 at screening.~Has organic mental disorders, or mental disorders due to a general medical condition (per DSM-5 criteria).~Has a current diagnosis or history of substance use disorder including alcohol use disorder (excluding nicotine and caffeine) (per DSM-5 criteria) within the 12 months prior to screening; or is assessed by the Investigator as having regularly consumed alcohol exceeding 21 units for males and 14 units for females per week (1 unit equals 340 mL of beer, 115 mL of wine, or 43 mL of spirits) within the 12 months prior to screening.~Is currently using, or has a positive result on the drug screening at the Screening Visit for drugs of abuse (alcohol, opiates, methadone, cocaine, methamphetamine [including ecstasy], phencyclidine, propoxyphene, methylphenidate, barbiturates, and benzodiazepines). If subject's serum drug screen for ethanol is positive at Screening (V1) and the investigator determines subject does not have alcohol use disorder, then the subject may have a repeat serum drug screen for ethanol performed before baseline within the allotted screening period (results must be received prior to V2 baseline). If second serum drug screen for ethanol is positive, subject is excluded from participating in the study, however, if second serum drug screen for ethanol is negative, subject may proceed to V2.~Is a (known or self-identified) current habitual/chronic cannabis user (medicinal or recreational); or~Has a positive urine drug screen for cannabis at the Screening Visit and is considered, per the Investigator's judgement, to be a habitual/chronic cannabis user; or~Has a positive urine drug screen for cannabis at both the screening and follow-up drug screen at the Baseline Visit, even though the subject is not considered, per the Investigator's judgement, to be a habitual/chronic cannabis user.~Note: Subjects who have a positive urine drug screen for cannabis at the Screening Visit but who are not considered to be a habitual/chronic cannabis user per the Investigator's judgement may, with Sponsor approval, undergo an additional urine drug screen at least 4 weeks after the original urine drug screen at Baseline Visit, prior to randomization. Subjects must agree to refrain from cannabis use throughout study.~Has treatment-resistant ADHD based on a history of receipt of >2 approved ADHD medications that failed to adequately improve the subject's symptoms. A subject who is naïve to ADHD treatment is not excluded from study participation.~Has any other disorder for which its treatment takes priority over treatment of ADHD or is likely to interfere with study treatment, impair treatment compliance, or interfere with interpretation of study results.~Has history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin that has not been in remission for > 5 years prior to the first dose of SM.~Has or has had one or more of the following conditions considered clinically significant/relevant by the Investigator in the context of the study:~cardiovascular disease~congestive heart failure~cardiac hypertrophy~arrhythmia~bradycardia (pulse < 50 bpm)~tachycardia (pulse > 100 bpm)~respiratory disease~hepatic impairment or renal insufficiency~metabolic disorder~endocrine disorder~gastrointestinal disorder~hematological disorder~infectious disorder~any clinically significant immunological condition~dermatological disorder~Exhibits clinically significant abnormal vital signs at screening.~Has one or more screening clinical laboratory test values outside the reference range that, in the opinion of the Investigator, are clinically significant, or any of the following:~Serum creatinine > 1.5 times the upper limit of normal (ULN);~Serum total bilirubin > 1.5 times ULN;~Serum alanine aminotransferase or aspartate aminotransferase > 2 times ULN.~Has any of the following cardiology findings at screening:~Abnormal ECG that is, in the Investigator's opinion, clinically significant;~PR interval > 220 ms;~QRS interval > 130 ms;~QTcF interval > 450 ms (for men) or > 470 ms (for women) (QT corrected using Fridericia's method);~Second- or third-degree atrioventricular block;~Any rhythm, other than sinus rhythm, that is interpreted by the Investigator to be clinically significant.~Has any disease or medication that could, in the Investigator's opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with study conduct or interpretation of results.~Evidence of infection with hepatitis B or C, or human immunodeficiency virus (HIV)-1 or HIV-2, as determined by results of testing at screening.~Lost or donated more than 450 mL of blood during the 30 days prior to screening.~Use of any investigational drug or prohibited concomitant medications including known CYP1A2 substrates (e.g., theophylline, melatonin) within 30 days or 5 half-lives prior to Baseline Visit (Day 1) (whichever is longer) during the screening period or anticipated for the duration of the study.~History of unexplained loss of consciousness, unexplained syncope, unexplained irregular heartbeats or palpitations or near drowning with hospital admission.~Has attempted suicide within the 6 months prior to screening, or is at significant risk of suicide, either in the opinion of the Investigator or defined as a yes to suicidal ideation questions 4 or 5 or answering yes to suicidal behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) within the 6 months prior to screening.~In the Investigator's opinion, is unlikely to comply with the protocol or is unsuitable for any other reason.
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of SPN-812 on Symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score | The Primary Endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) Total score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. A Total score is calculated by summating the ratings of all 18 items (range: 0-54; the higher the score, the more severe the ADHD symptoms). A lower change from baseline AISRS Total score (<0) represents a better outcome. | Baseline and Week 6 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of SPN-812 on the Clinical Global Impression - Severity of Illness (CGI-S) Scale | The Key Secondary Endpoint was the change from baseline in the Clinical Global Impression - Severity of Illness (CGI-S) score at Week 6. The CGI-S is a single item clinician-rated assessment of the severity of subject's condition (ADHD symptoms) in relation to the clinician's total experience with patients with ADHD. The CGI-S is evaluated on a 7-point scale with 1 = Normal, not at all ill, asymptomatic, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Among the most extremely ill patients. Successful therapy is indicated by a lower overall score in subsequent testing. A lower change from baseline CGI-S score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Clinical Response Rate as Assessed by the Clinical Global Impression - Severity of Illness (CGI-S) Scale | An additional secondary endpoint was the percentage of subjects with a Clinical Global Impression - Severity of Illness (CGI-S) score of 1 or 2 (responders) at Week 6. The CGI-S is a single item clinician-rated assessment of the severity of subject's condition (ADHD symptoms) in relation to the clinician's total experience with patients with ADHD. The CGI-S is evaluated on a 7-point scale with 1 = Normal, not at all ill, asymptomatic, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Among the most extremely ill patients. Responder rate values range from 0 to 100%. A higher percentage represents a greater number of subjects who are responders. | Week 6 |
| Effect of SPN-812 on the Clinical Global Impression - Improvement (CGI-I) Scale | An additional secondary endpoint was the Clinical Global Impression - Improvement (CGI-I) score at Week 6. The CGI-I scale is a single item clinician-rated assessment of how much the subject's condition (ADHD) has improved, worsened or has not changed relative to his/her baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point scale from 1 to 7, where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. A CGI-I score <4 represents a better outcome. | Week 6 |
| Effect of SPN-812 on Clinical Response Rate as Assessed by the Clinical Global Impression - Improvement (CGI-I) Scale | An additional secondary endpoint was the percentage of subjects with a CGI-I score of 1 or 2 (responders) at Week 6. The CGI-I scale is a single item clinician-rated assessment of how much the subject's condition (ADHD) has improved, worsened or has not changed relative to his/her baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point scale from 1 to 7, where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Responder rate values can range from 0 to 100%. A higher percentage represents a greater number of subjects who are responders. | Week 6 |
| Effect of SPN-812 on Symptoms of Anxiety as Assessed by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale | An additional secondary endpoint was the change from baseline in the Generalized Anxiety Disorder 7-Item (GAD-7) Total score at Week 6. The GAD-7 is a self-reported 7-item questionnaire for screening and measuring the severity of generalized anxiety disorder. The subject rates each item on 4-point scale (0-3), where 0 = Not at all, 1 = Several days, 2 = Over half the days, and 3 = Nearly every day. The total score is calculated by summated the ratings of all 7 items. The total score can range between 0 to 21; the higher the score, the more severe the symptoms of anxiety. A lower change from baseline GAD-7 total score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on Inattention Symptoms as Assessed by the Inattention Subscale of the Adult ADHD Investigator Symptom Rating Scale (AISRS) | An additional secondary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) Inattention subscale score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. The Inattention subscale score is calculated by summating the ratings of all 9 Inattention items (range: 0-27; the higher the score, the more severe the symptoms). A lower change from baseline Inattention subscale score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on Hyperactivity/Impulsivity Symptoms as Assessed by the Hyperactivity/Impulsivity Subscale of the Adult ADHD Investigator Symptom Rating Scale (AISRS) | An additional secondary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) Hyperactivity/Impulsivity subscale score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. The Hyperactivity/Impulsivity subscale score is calculated by summating the ratings of all 9 Hyperactivity/Impulsivity items (range: 0-27; the higher the score, the more severe the symptoms). A lower change from baseline Hyperactivity/Impulsivity subscale score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on 30% Clinical Response Rate as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS) | An additional secondary endpoint was the percentage of subjects with a 30% or greater reduction in their change from baseline Adult ADHD Investigator Symptom Rating Scale (AISRS) Total score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. A Total score is calculated by summating the ratings of all 18 items (range: 0-54; the higher the score, the more severe the symptoms). The Total score is converted to a percent change from baseline. 30% responder rate values can range between 0 and 100%. A higher percentage represents a greater number of subjects who are responders. | Baseline and Week 6 |
| Effect of SPN-812 on 50% Clinical Response Rate as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS). | An additional secondary endpoint was the percentage of subjects with a 50% or greater reduction in their change from baseline Adult ADHD Investigator Symptom Rating Scale (AISRS) Total score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. A Total score is calculated by summating the ratings of all 18 items (range: 0-54; the higher the score, the more severe the symptoms). The Total score is converted to a percent change from baseline. 50% responder rate values can range between 0 and 100%. A higher percentage represents a greater number of subjects who are responders. | Baseline and Week 6 |
| Effect of SPN-812 on the Global Executive Composite (GEC) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Global Executive Composite (GEC) T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning (GEC) and 9 non-overlapping scales among 2 summary index scales (Metacognition Index [MI] and Behavioral Regulation Index [BRI]) that assess aspects of executive function and problems with self-regulation from the perspective of the individual. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 70 items yields the GEC raw score (range: 70-210), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline GEC T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Behavioral Regulation Index (BRI) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Behavioral Regulation Index (BRI) T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The BRI captures the ability to maintain appropriate regulatory control of one's own behavior and emotional responses. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 30 items yields the BRI raw score (range: 30-90), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline BRI T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Metacognitive Index (MI) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Metacognition Index (MI) T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. MI reflects individual's ability to problem solve (includes initiate activity, generate ideas, sustain working memory, plan/organize approaches, monitor success/failure, and organize materials/environment). Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 40 items yields the MI raw score (range: 40-120), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline MI T-score (<0) represents a better outcome. | Baseline and week 6 |
| Effect of SPN-812 on the Inhibit Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Inhibit scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Inhibit scale is one of four Behavioral Regulation Index-related scales; it captures the ability to control impulses, appropriately stop verbal, attentional, physical behavior at the proper time. Subject's rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 8 items yields the Inhibit raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Inhibit T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Shift Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Shift scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Shift scale is one of four Behavioral Regulation Index-related scales; it captures one's ability to move freely from one situation/activity/aspect of problem to another and think flexibly to aid problem-solving. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 6 items yields the Shift raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Shift T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Emotional Control Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Emotional Control scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Emotional Control scale is one of four Behavioral Regulation Index-related scales; it captures an individual's ability to modulate their emotional responses appropriately. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 10 items yields the Emotional Control raw score (range: 10-30), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Emotional Control T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Self-Monitor Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Monitor scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Self-Monitor scale is one of four Behavioral Regulation Index-related scales; it reflects an individual's ability to recognize the effect of their own behavior on others. The subject rates each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 6 items yields the Self-Monitor raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Self-Monitor T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Initiate Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Initiate scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Initiate scale is one of five Metacognition Index-related scales; it captures an individual's ability to begin a task or activity without external prompting and to independently generate ideas. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 8 items yields the Initiate scale raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Initiate T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Plan/Organize Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Plan/Organize scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Plan/Organize scale is one of five Metacognition Index-related scales; it captures an individual's ability to anticipate events, set goals, pre-plan, organize, and carry out tasks systematically. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience within the last month. The sum of 10 items yields the Plan/Organize raw score (range: 10-30), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Plan/Organize T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Task Monitor Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Task Monitor scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Task Monitor scale is one of five Metacognition Index-related scales; it captures an individual's ability to assess performance for mistakes during or after finishing a task. The subject rates each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 6 items yields the Task Monitor raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Task Monitor T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Organization of Materials Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Organization of Materials scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Organization of Materials scale is one of five Metacognition Index-related scales; it captures one's ability to keep areas orderly and maintain materials. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience within the last month. The sum of 8 items yields the Organization of Materials raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Organization of Materials T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Working Memory Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Working Memory scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Working Memory scale is one of five Metacognition Index-related scales; it captures one's ability to hold information in mind in order to complete a task and stay with, or stick to, an activity. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience within the last month. The sum of 8 items yields the Working Memory raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Working Memory T-score (<0) represents a better outcome. | Baseline and Week 6 |
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Attention-Deficit/Hyperactivity Disorder (ADHD), Adult ADHD,
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Viloxazine, Antidepressive Agents, Second-Generation, Antidepressive Agents, Psychotropic Drugs, Adrenergic Uptake Inhibitors, Neurotransmitter Uptake Inhibitors, Membrane Transport Modulators, Molecular Mechanisms of Pharmacological Action, Adrenergic Agents, Neurotransmitter Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo, qd, oral capsule | Drug: Placebo<br>* Placebo will be administered once daily<br>* Other names: PBO;|
| Experimental: SPN-812<br>SPN-812, qd, oral capsule | Drug: SPN-812<br>* SPN-812 will be administered once daily and compared to Placebo<br>* Other names: Viloxazine extended-release capsules;|
|
Evaluation of SPN-812 (Viloxazine Extended-release Capsule) in Adults With ADHD
Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of SPN-812 (Viloxazine extended-release capsules; 200-600 mg) in adults 18-65 years of age with Attention-Deficit/Hyperactivity Disorder (ADHD).
Detailed Description
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This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, 2-arm, parallel-group, flexible dose trial assessing the efficacy and safety of SPN-812 (Viloxazine extended-release capsules; 200-600 mg) as monotherapy for the treatment of adults 18-65 years old with Attention-Deficit/Hyperactivity Disorder (ADHD).
Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Flexible-Dose Study of the Efficacy and Safety of SPN-812 in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)
Conditions
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Attention-Deficit/Hyperactivity Disorder (ADHD)
Intervention / Treatment
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* Drug: Placebo
* Drug: SPN-812
Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is male or female, aged 18 to ≤ 65 years at screening. Is able to read and understand the Informed Consent Form (ICF). Written informed consent obtained from the subject (a signed ICF). Weight within the normal or overweight ranges according to accepted values of the Body Mass Index Chart (18.0 to 35 kg/m2). Is able to swallow capsules whole, without crushing, chewing or cutting. Is willing and able to attend study appointments within the specified time windows. Has a primary diagnosis of ADHD according to the DSM-5 classification, with diagnosis made at least 6 months prior to screening and confirmed with Structured Clinical Interview for DSM-5 Clinical Trials version (SCID-5-CT). Has an AISRS Adult ADHD (Attention-Deficit/Hyperactivity Disorder) Investigator Symptom Rating Scale total score of ≥ 26 at the Screening Visit and at the Baseline Visit (V2, Day 1). Has a CGI-S score of ≥ 4 (moderately ill or worse) at the Screening Visit (V1) and Baseline Visit (V2, Day 1). Females of childbearing potential (FOCP) must be either sexually inactive (abstinent) or, if sexually active, must agree to use one of the following acceptable birth control methods beginning 30 days prior to the first dose of SM and throughout the study: Simultaneous use of male condom and intra-uterine contraceptive device placed at least 4 weeks prior to first SM administration Surgically sterile male partner Simultaneous use of male condom and diaphragm with spermicide Established hormonal contraceptive Females are considered not to be of childbearing potential if they are either post-menopausal (amenorrhea for at least 2 years and serum follicle stimulating hormone (FSH) level of >40 IU/L) or permanently sterilized (e.g., bilateral tubal ligation, hysterectomy, bilateral oophorectomy for 6 months minimum prior to screening). Males must: Use 2 methods of contraception in combination if his female partner is of childbearing potential; this combination of contraceptive methods must be used from the Baseline Visit to ≥ 1 month after the last dose of SM, or Have been surgically sterilized prior to the Screening Visit. Exclusion Criteria: Has previously enrolled in a SPN-812 study. Is currently participating in another clinical trial or has participated in a clinical trial within 60 days prior to the first Screening Visit. Is a member of the study personnel or of their immediate families, or is a subordinate (or immediate family member of a subordinate) to any of the study personnel. Female subjects who are pregnant, lactating and/or sexually active and not agreeing to use one of the acceptable birth control methods throughout the study. Has history of severe drug allergy or hypersensitivity, or known hypersensitivity, to the study medication or excipients. Has history of moderate or severe head trauma or other neurological disorder or systemic medical disease that, in the Investigator's opinion, is likely to affect central nervous system functioning. This would include subjects with: A current diagnosis of a major neurological disorder; or Seizures, seizure disorder or seizure-like events; or a history of seizure disorder within the immediate family (siblings, parents); or Encephalopathy Has any history of schizophrenia, schizoaffective disorder, bipolar disorder, borderline personality disorder, antisocial personality disorder, narcissistic personality disorder, autism, post-traumatic stress disorder or obsessive-compulsive disorder. Has any current psychiatric disorder (per DSM-5 criteria) other than ADHD with the following exceptions: ADHD is primary diagnosis with comorbidity/secondary diagnoses of major depression disorder (MDD), nicotine dependence, social anxiety disorder, generalized anxiety disorder, or phobias, and subject is not receiving pharmacological treatment for the comorbidity/secondary diagnoses (e.g., antidepressant for MDD) at time of screening nor for the duration of study. Has a Symptoms of Depression Questionnaire (SDQ) mean score >3.0 at screening. Has a Hamilton Anxiety Rating Scale (HAM-A) score of > 21 at screening. Has organic mental disorders, or mental disorders due to a general medical condition (per DSM-5 criteria). Has a current diagnosis or history of substance use disorder including alcohol use disorder (excluding nicotine and caffeine) (per DSM-5 criteria) within the 12 months prior to screening; or is assessed by the Investigator as having regularly consumed alcohol exceeding 21 units for males and 14 units for females per week (1 unit equals 340 mL of beer, 115 mL of wine, or 43 mL of spirits) within the 12 months prior to screening. Is currently using, or has a positive result on the drug screening at the Screening Visit for drugs of abuse (alcohol, opiates, methadone, cocaine, methamphetamine [including ecstasy], phencyclidine, propoxyphene, methylphenidate, barbiturates, and benzodiazepines). If subject's serum drug screen for ethanol is positive at Screening (V1) and the investigator determines subject does not have alcohol use disorder, then the subject may have a repeat serum drug screen for ethanol performed before baseline within the allotted screening period (results must be received prior to V2 baseline). If second serum drug screen for ethanol is positive, subject is excluded from participating in the study, however, if second serum drug screen for ethanol is negative, subject may proceed to V2. Is a (known or self-identified) current habitual/chronic cannabis user (medicinal or recreational); or Has a positive urine drug screen for cannabis at the Screening Visit and is considered, per the Investigator's judgement, to be a habitual/chronic cannabis user; or Has a positive urine drug screen for cannabis at both the screening and follow-up drug screen at the Baseline Visit, even though the subject is not considered, per the Investigator's judgement, to be a habitual/chronic cannabis user. Note: Subjects who have a positive urine drug screen for cannabis at the Screening Visit but who are not considered to be a habitual/chronic cannabis user per the Investigator's judgement may, with Sponsor approval, undergo an additional urine drug screen at least 4 weeks after the original urine drug screen at Baseline Visit, prior to randomization. Subjects must agree to refrain from cannabis use throughout study. Has treatment-resistant ADHD based on a history of receipt of >2 approved ADHD medications that failed to adequately improve the subject's symptoms. A subject who is naïve to ADHD treatment is not excluded from study participation. Has any other disorder for which its treatment takes priority over treatment of ADHD or is likely to interfere with study treatment, impair treatment compliance, or interfere with interpretation of study results. Has history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin that has not been in remission for > 5 years prior to the first dose of SM. Has or has had one or more of the following conditions considered clinically significant/relevant by the Investigator in the context of the study: cardiovascular disease congestive heart failure cardiac hypertrophy arrhythmia bradycardia (pulse < 50 bpm) tachycardia (pulse > 100 bpm) respiratory disease hepatic impairment or renal insufficiency metabolic disorder endocrine disorder gastrointestinal disorder hematological disorder infectious disorder any clinically significant immunological condition dermatological disorder Exhibits clinically significant abnormal vital signs at screening. Has one or more screening clinical laboratory test values outside the reference range that, in the opinion of the Investigator, are clinically significant, or any of the following: Serum creatinine > 1.5 times the upper limit of normal (ULN); Serum total bilirubin > 1.5 times ULN; Serum alanine aminotransferase or aspartate aminotransferase > 2 times ULN. Has any of the following cardiology findings at screening: Abnormal ECG that is, in the Investigator's opinion, clinically significant; PR interval > 220 ms; QRS interval > 130 ms; QTcF interval > 450 ms (for men) or > 470 ms (for women) (QT corrected using Fridericia's method); Second- or third-degree atrioventricular block; Any rhythm, other than sinus rhythm, that is interpreted by the Investigator to be clinically significant. Has any disease or medication that could, in the Investigator's opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with study conduct or interpretation of results. Evidence of infection with hepatitis B or C, or human immunodeficiency virus (HIV)-1 or HIV-2, as determined by results of testing at screening. Lost or donated more than 450 mL of blood during the 30 days prior to screening. Use of any investigational drug or prohibited concomitant medications including known CYP1A2 substrates (e.g., theophylline, melatonin) within 30 days or 5 half-lives prior to Baseline Visit (Day 1) (whichever is longer) during the screening period or anticipated for the duration of the study. History of unexplained loss of consciousness, unexplained syncope, unexplained irregular heartbeats or palpitations or near drowning with hospital admission. Has attempted suicide within the 6 months prior to screening, or is at significant risk of suicide, either in the opinion of the Investigator or defined as a yes to suicidal ideation questions 4 or 5 or answering yes to suicidal behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) within the 6 months prior to screening. In the Investigator's opinion, is unlikely to comply with the protocol or is unsuitable for any other reason.
Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years
Sexes Eligible for Study
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All
Accepts Healthy Volunteers
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No
Study Plan
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How is the study designed?
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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>Placebo, qd, oral capsule | Drug: Placebo<br>* Placebo will be administered once daily<br>* Other names: PBO;|
| Experimental: SPN-812<br>SPN-812, qd, oral capsule | Drug: SPN-812<br>* SPN-812 will be administered once daily and compared to Placebo<br>* Other names: Viloxazine extended-release capsules;|
What is the study measuring?
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Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of SPN-812 on Symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS) Total Score | The Primary Endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) Total score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. A Total score is calculated by summating the ratings of all 18 items (range: 0-54; the higher the score, the more severe the ADHD symptoms). A lower change from baseline AISRS Total score (<0) represents a better outcome. | Baseline and Week 6 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of SPN-812 on the Clinical Global Impression - Severity of Illness (CGI-S) Scale | The Key Secondary Endpoint was the change from baseline in the Clinical Global Impression - Severity of Illness (CGI-S) score at Week 6. The CGI-S is a single item clinician-rated assessment of the severity of subject's condition (ADHD symptoms) in relation to the clinician's total experience with patients with ADHD. The CGI-S is evaluated on a 7-point scale with 1 = Normal, not at all ill, asymptomatic, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Among the most extremely ill patients. Successful therapy is indicated by a lower overall score in subsequent testing. A lower change from baseline CGI-S score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Clinical Response Rate as Assessed by the Clinical Global Impression - Severity of Illness (CGI-S) Scale | An additional secondary endpoint was the percentage of subjects with a Clinical Global Impression - Severity of Illness (CGI-S) score of 1 or 2 (responders) at Week 6. The CGI-S is a single item clinician-rated assessment of the severity of subject's condition (ADHD symptoms) in relation to the clinician's total experience with patients with ADHD. The CGI-S is evaluated on a 7-point scale with 1 = Normal, not at all ill, asymptomatic, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Among the most extremely ill patients. Responder rate values range from 0 to 100%. A higher percentage represents a greater number of subjects who are responders. | Week 6 |
| Effect of SPN-812 on the Clinical Global Impression - Improvement (CGI-I) Scale | An additional secondary endpoint was the Clinical Global Impression - Improvement (CGI-I) score at Week 6. The CGI-I scale is a single item clinician-rated assessment of how much the subject's condition (ADHD) has improved, worsened or has not changed relative to his/her baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point scale from 1 to 7, where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. A CGI-I score <4 represents a better outcome. | Week 6 |
| Effect of SPN-812 on Clinical Response Rate as Assessed by the Clinical Global Impression - Improvement (CGI-I) Scale | An additional secondary endpoint was the percentage of subjects with a CGI-I score of 1 or 2 (responders) at Week 6. The CGI-I scale is a single item clinician-rated assessment of how much the subject's condition (ADHD) has improved, worsened or has not changed relative to his/her baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point scale from 1 to 7, where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Responder rate values can range from 0 to 100%. A higher percentage represents a greater number of subjects who are responders. | Week 6 |
| Effect of SPN-812 on Symptoms of Anxiety as Assessed by the Generalized Anxiety Disorder 7-Item (GAD-7) Scale | An additional secondary endpoint was the change from baseline in the Generalized Anxiety Disorder 7-Item (GAD-7) Total score at Week 6. The GAD-7 is a self-reported 7-item questionnaire for screening and measuring the severity of generalized anxiety disorder. The subject rates each item on 4-point scale (0-3), where 0 = Not at all, 1 = Several days, 2 = Over half the days, and 3 = Nearly every day. The total score is calculated by summated the ratings of all 7 items. The total score can range between 0 to 21; the higher the score, the more severe the symptoms of anxiety. A lower change from baseline GAD-7 total score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on Inattention Symptoms as Assessed by the Inattention Subscale of the Adult ADHD Investigator Symptom Rating Scale (AISRS) | An additional secondary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) Inattention subscale score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. The Inattention subscale score is calculated by summating the ratings of all 9 Inattention items (range: 0-27; the higher the score, the more severe the symptoms). A lower change from baseline Inattention subscale score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on Hyperactivity/Impulsivity Symptoms as Assessed by the Hyperactivity/Impulsivity Subscale of the Adult ADHD Investigator Symptom Rating Scale (AISRS) | An additional secondary endpoint was the change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) Hyperactivity/Impulsivity subscale score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The scale is subdivided into two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. The Hyperactivity/Impulsivity subscale score is calculated by summating the ratings of all 9 Hyperactivity/Impulsivity items (range: 0-27; the higher the score, the more severe the symptoms). A lower change from baseline Hyperactivity/Impulsivity subscale score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on 30% Clinical Response Rate as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS) | An additional secondary endpoint was the percentage of subjects with a 30% or greater reduction in their change from baseline Adult ADHD Investigator Symptom Rating Scale (AISRS) Total score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. A Total score is calculated by summating the ratings of all 18 items (range: 0-54; the higher the score, the more severe the symptoms). The Total score is converted to a percent change from baseline. 30% responder rate values can range between 0 and 100%. A higher percentage represents a greater number of subjects who are responders. | Baseline and Week 6 |
| Effect of SPN-812 on 50% Clinical Response Rate as Assessed by the Adult ADHD Investigator Symptom Rating Scale (AISRS). | An additional secondary endpoint was the percentage of subjects with a 50% or greater reduction in their change from baseline Adult ADHD Investigator Symptom Rating Scale (AISRS) Total score at Week 6. The AISRS is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology in adults. The AISRS consists of 18 items that directly correspond to the 18 symptoms of ADHD per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The clinician/investigator rates the subject on each item using a 4-point scale, where 0=none, 1=mild, 2=moderate, and 3=severe. A Total score is calculated by summating the ratings of all 18 items (range: 0-54; the higher the score, the more severe the symptoms). The Total score is converted to a percent change from baseline. 50% responder rate values can range between 0 and 100%. A higher percentage represents a greater number of subjects who are responders. | Baseline and Week 6 |
| Effect of SPN-812 on the Global Executive Composite (GEC) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Global Executive Composite (GEC) T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning (GEC) and 9 non-overlapping scales among 2 summary index scales (Metacognition Index [MI] and Behavioral Regulation Index [BRI]) that assess aspects of executive function and problems with self-regulation from the perspective of the individual. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 70 items yields the GEC raw score (range: 70-210), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline GEC T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Behavioral Regulation Index (BRI) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Behavioral Regulation Index (BRI) T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The BRI captures the ability to maintain appropriate regulatory control of one's own behavior and emotional responses. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 30 items yields the BRI raw score (range: 30-90), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline BRI T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Metacognitive Index (MI) of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Metacognition Index (MI) T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. MI reflects individual's ability to problem solve (includes initiate activity, generate ideas, sustain working memory, plan/organize approaches, monitor success/failure, and organize materials/environment). Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 40 items yields the MI raw score (range: 40-120), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline MI T-score (<0) represents a better outcome. | Baseline and week 6 |
| Effect of SPN-812 on the Inhibit Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Inhibit scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Inhibit scale is one of four Behavioral Regulation Index-related scales; it captures the ability to control impulses, appropriately stop verbal, attentional, physical behavior at the proper time. Subject's rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 8 items yields the Inhibit raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Inhibit T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Shift Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Shift scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Shift scale is one of four Behavioral Regulation Index-related scales; it captures one's ability to move freely from one situation/activity/aspect of problem to another and think flexibly to aid problem-solving. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 6 items yields the Shift raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Shift T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Emotional Control Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Emotional Control scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Emotional Control scale is one of four Behavioral Regulation Index-related scales; it captures an individual's ability to modulate their emotional responses appropriately. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 10 items yields the Emotional Control raw score (range: 10-30), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Emotional Control T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Self-Monitor Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Monitor scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Self-Monitor scale is one of four Behavioral Regulation Index-related scales; it reflects an individual's ability to recognize the effect of their own behavior on others. The subject rates each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 6 items yields the Self-Monitor raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Self-Monitor T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Initiate Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Initiate scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Initiate scale is one of five Metacognition Index-related scales; it captures an individual's ability to begin a task or activity without external prompting and to independently generate ideas. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 8 items yields the Initiate scale raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Initiate T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Plan/Organize Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Plan/Organize scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Plan/Organize scale is one of five Metacognition Index-related scales; it captures an individual's ability to anticipate events, set goals, pre-plan, organize, and carry out tasks systematically. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience within the last month. The sum of 10 items yields the Plan/Organize raw score (range: 10-30), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Plan/Organize T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Task Monitor Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Task Monitor scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Task Monitor scale is one of five Metacognition Index-related scales; it captures an individual's ability to assess performance for mistakes during or after finishing a task. The subject rates each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on their experience within the last month. The sum of 6 items yields the Task Monitor raw score (range: 6-18), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Task Monitor T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Organization of Materials Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Organization of Materials scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Organization of Materials scale is one of five Metacognition Index-related scales; it captures one's ability to keep areas orderly and maintain materials. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience within the last month. The sum of 8 items yields the Organization of Materials raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Organization of Materials T-score (<0) represents a better outcome. | Baseline and Week 6 |
| Effect of SPN-812 on the Working Memory Scale of the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) | An additional secondary endpoint was the change from baseline in the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Working Memory scale T-score at Week 6. The BRIEF-A is a 75-item self-rating scale that assesses overall functioning and 9 non-overlapping scales among 2 summary index scales. The Working Memory scale is one of five Metacognition Index-related scales; it captures one's ability to hold information in mind in order to complete a task and stay with, or stick to, an activity. Subjects rate each item on a 3-point scale (1=Never, 2=Sometimes, 3=Often) based on their experience within the last month. The sum of 8 items yields the Working Memory raw score (range: 8-24), which is converted to a T-score (normative population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally elevated). T-score is converted to a change from baseline T-score. A lower change from baseline Working Memory T-score (<0) represents a better outcome. | Baseline and Week 6 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Attention-Deficit/Hyperactivity Disorder (ADHD), Adult ADHD,
|
NCT02602964
|
A Trial Comparing Deep Versus Moderate Neuromuscular Block - in Low Pressure Pneumoperitoneum
|
Live kidney transplantation is first choice for patients with end-stage kidney disease. Therefore, the safety and well-being of kidneys donors are highly important objectives in live kidney donation. Low pressure pneumoperitoneum can decrease postoperative pain and therefore also concomitant use of opioids.
|
However low pressure pneumoperitoneum can also decrease peri-operative conditions. In this trial the researchers will investigate whether peri-operative conditions during low pressure pneumoperitoneum can be optimized by the use of deep neuromuscular block.
|
A Randomized Controlled Trial Comparing Deep Versus Moderate Neuromuscular Block - in Low Pressure Pneumoperitoneum - to Optimize the Surgical Conditions During Laparoscopic Donor Nephrectomy
|
Nephrostomy; Complications, Pneumoperitoneum, Observation of Neuromuscular Block
|
* Other: Deep neuromsucular block
|
Inclusion Criteria:~obtained informed consent~age over 18 years~Exclusion Criteria:~chronic use of analgesics or psychotropic drugs~use of non-steroidal anti-inflammatory drugs shorter than 5 days before surgery~known or suspect allergy to rocuronium or sugammadex~significant liver or renal dysfunction~pregnant or breastfeeding
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean surgical rating score | | perioperative |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conversion to standard pressure pneumoperitoneum | | perioperative |
| Intra-operative complications | | perioperative |
| Length of pneumoperitoneum | | perioperative |
|
Pneumoperitoneum, Peritoneal Diseases, Digestive System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep neuromsucular block<br>Deep neuromuscular block and low pressure pneumoperitoneum | Other: Deep neuromsucular block<br>* Deep or standard neuromuscular block<br>|
| No Intervention: Standard neuromuscular block<br>Standard neuromuscular block and low pressure pneumoperitoneum | |
|
A Trial Comparing Deep Versus Moderate Neuromuscular Block - in Low Pressure Pneumoperitoneum
Study Overview
=================
Brief Summary
-----------------
Live kidney transplantation is first choice for patients with end-stage kidney disease. Therefore, the safety and well-being of kidneys donors are highly important objectives in live kidney donation. Low pressure pneumoperitoneum can decrease postoperative pain and therefore also concomitant use of opioids.
Detailed Description
-----------------
However low pressure pneumoperitoneum can also decrease peri-operative conditions. In this trial the researchers will investigate whether peri-operative conditions during low pressure pneumoperitoneum can be optimized by the use of deep neuromuscular block.
Official Title
-----------------
A Randomized Controlled Trial Comparing Deep Versus Moderate Neuromuscular Block - in Low Pressure Pneumoperitoneum - to Optimize the Surgical Conditions During Laparoscopic Donor Nephrectomy
Conditions
-----------------
Nephrostomy; Complications, Pneumoperitoneum, Observation of Neuromuscular Block
Intervention / Treatment
-----------------
* Other: Deep neuromsucular block
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: obtained informed consent age over 18 years Exclusion Criteria: chronic use of analgesics or psychotropic drugs use of non-steroidal anti-inflammatory drugs shorter than 5 days before surgery known or suspect allergy to rocuronium or sugammadex significant liver or renal dysfunction pregnant or breastfeeding
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: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep neuromsucular block<br>Deep neuromuscular block and low pressure pneumoperitoneum | Other: Deep neuromsucular block<br>* Deep or standard neuromuscular block<br>|
| No Intervention: Standard neuromuscular block<br>Standard neuromuscular block and low pressure pneumoperitoneum | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean surgical rating score | | perioperative |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conversion to standard pressure pneumoperitoneum | | perioperative |
| Intra-operative complications | | perioperative |
| Length of pneumoperitoneum | | perioperative |
|
|
NCT00980135
|
Sinecort Pilot Efficacy Study
|
The study shall prove whether treatment of atopic dermatitis is equally effective with Sinecort cream as compared to standard therapy (Hydrocortisone cream).
|
An Investigator-blind, Randomized, Monocentre, 3-arm, Active Controlled Pilot Trial to Explore the Efficacy and Safety of a New Topical Medical Device in Patients With Mild Atopic Dermatitis in an Intra-individual Comparison With a Standard Therapy (1% Hydrocortisone Cream) and Untreated Skin.
|
Atopic Dermatitis
|
* Device: Sinecort cream
* Drug: Hydrocortison cream
* Other: Untreated skin
|
Inclusion Criteria:~Male or female Caucasians aged between 18 and 65 years~Patients with mild AD presenting a scoring AD (SCORAD) rating between 3-25~Skin type I - IV according to Fitzpatrick~Acute AD symptoms on each assessment areas (local SCORAD >/=3 and <= 12)~Acute symptom of pruritus at Baseline~Exclusion Criteria:~Any other skin disease at the test area that would interfere the clinical assessment in the opinion of the investigator~Moles, tattoos, strong pigmentation, or scars at the test area that would interfere the clinical assessment~Regular intake of antiphlogistic drugs (for example, NSAIDs)~Any condition or treatment which might influence the trial (e.g. any treatment with topical antibiotics, antifungals, or corticoids) within 14 days prior to screening as well as during the trial (exception: topical treatment of AD lesions other than the test areas (for example, face) with low potency steroids restricted to small areas)~UV-therapy or the use of solarium within 30 days before screening as well as during the trial~Any alternative treatment of AD (e.g. acupuncture, kinesiology, and homoeopathy) within 30 days before screening as well as during the trial
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy rate versus comparator and untreated skin | | After 29 days of twice daily applications |
| Local side effects on the skin | | 29 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local SCORAD as clinical assessment by means of the intensity items of the SCORAD index) at Visit 2 through Visit 6 | | after 29 days |
| Transepidermal water loss (TEWL) as a measure for skin barrier function at Visit 2 through Visit 6 | | after 29 days |
| Skin hydration by means of corneometry at visit 2 through visit 6 | | after 29 days |
| Erythema by means of chromametry at Visit 2 through Visit 6 | | after 29 days |
| Intensity of pruritus at each day of the dosing period (day 1- day 29) as reported in the patients diary and at Visit 2 through Vist 6 by means of visual analogue scale (VAS) | | after 29 days |
| Incidence and severity of Adverse Event | | visit 2 (start of dosing period) till 6 weeks after end of treatment |
| Vital signs | | visit1 and 6 weeks after end of treatment |
| Local side effects | | visit 2 (start of dosing period) till 6 weeks after end of treatment |
|
Sinecort, Hydrocortison, Mild atopic dermatitis, Efficacy, safety
|
Hydrocortisone, Anti-Inflammatory Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Device: Sinecort cream<br>* Application over 29 days<br>|
| Experimental: Arm 2<br> | Drug: Hydrocortison cream<br>* Application over 29 days<br>|
| Other: Arm 3<br> | Other: Untreated skin<br> <br> |
|
Sinecort Pilot Efficacy Study
Study Overview
=================
Brief Summary
-----------------
The study shall prove whether treatment of atopic dermatitis is equally effective with Sinecort cream as compared to standard therapy (Hydrocortisone cream).
Official Title
-----------------
An Investigator-blind, Randomized, Monocentre, 3-arm, Active Controlled Pilot Trial to Explore the Efficacy and Safety of a New Topical Medical Device in Patients With Mild Atopic Dermatitis in an Intra-individual Comparison With a Standard Therapy (1% Hydrocortisone Cream) and Untreated Skin.
Conditions
-----------------
Atopic Dermatitis
Intervention / Treatment
-----------------
* Device: Sinecort cream
* Drug: Hydrocortison cream
* Other: Untreated skin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female Caucasians aged between 18 and 65 years Patients with mild AD presenting a scoring AD (SCORAD) rating between 3-25 Skin type I - IV according to Fitzpatrick Acute AD symptoms on each assessment areas (local SCORAD >/=3 and <= 12) Acute symptom of pruritus at Baseline Exclusion Criteria: Any other skin disease at the test area that would interfere the clinical assessment in the opinion of the investigator Moles, tattoos, strong pigmentation, or scars at the test area that would interfere the clinical assessment Regular intake of antiphlogistic drugs (for example, NSAIDs) Any condition or treatment which might influence the trial (e.g. any treatment with topical antibiotics, antifungals, or corticoids) within 14 days prior to screening as well as during the trial (exception: topical treatment of AD lesions other than the test areas (for example, face) with low potency steroids restricted to small areas) UV-therapy or the use of solarium within 30 days before screening as well as during the trial Any alternative treatment of AD (e.g. acupuncture, kinesiology, and homoeopathy) within 30 days before screening as well as during the trial
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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Device: Sinecort cream<br>* Application over 29 days<br>|
| Experimental: Arm 2<br> | Drug: Hydrocortison cream<br>* Application over 29 days<br>|
| Other: Arm 3<br> | Other: Untreated skin<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy rate versus comparator and untreated skin | | After 29 days of twice daily applications |
| Local side effects on the skin | | 29 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local SCORAD as clinical assessment by means of the intensity items of the SCORAD index) at Visit 2 through Visit 6 | | after 29 days |
| Transepidermal water loss (TEWL) as a measure for skin barrier function at Visit 2 through Visit 6 | | after 29 days |
| Skin hydration by means of corneometry at visit 2 through visit 6 | | after 29 days |
| Erythema by means of chromametry at Visit 2 through Visit 6 | | after 29 days |
| Intensity of pruritus at each day of the dosing period (day 1- day 29) as reported in the patients diary and at Visit 2 through Vist 6 by means of visual analogue scale (VAS) | | after 29 days |
| Incidence and severity of Adverse Event | | visit 2 (start of dosing period) till 6 weeks after end of treatment |
| Vital signs | | visit1 and 6 weeks after end of treatment |
| Local side effects | | visit 2 (start of dosing period) till 6 weeks after end of treatment |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sinecort, Hydrocortison, Mild atopic dermatitis, Efficacy, safety
|
|
NCT02089919
|
Cancer Stem Cells Vaccine Therapy in Treating Hepatocellular Cancer Patients
|
Most studies of cancer stem cells (CSC) involve the inoculation of cells from human tumors into immunosuppressed mice, preventing an assessment on the immunologic interactions and effects of CSCs. In this study, the investigators examined the vaccination effects produced by CSC-enriched populations from histologically distinct murine tumors after their inoculation into different syngeneic immunocompetent hosts. Enriched CSCs were immunogenic and more effective as an antigen source than unselected tumor cells in inducing protective antitumor immunity.Immune sera from CSC-vaccinated hosts contained high levels of IgG which bound to CSCs, resulting in CSC lysis in the presence of complement.CTLs generated from peripheral blood mononuclear cells or splenocytes harvested from CSC-vaccinated hosts were capable of killing CSCs in vitro. Mechanistic investigations established that CSC-primed antibodies and T cells were capable of selective targeting CSCs and conferring anti-tumor immunity.
|
To assess the feasibility of generating CSC-loaded DC vaccines for clinical use, the investigators will harvest peripheral blood and tumor specimen from patients with hepatocellular cancer. The investigators will purify T, B cells and generate DCs from the PBMCs of the hepatocellular cancer patient.On the other hand, investigators will isolate ALDHhigh and ALDHlow tumor cells from the tumor specimen of the hepatocellular cancer patient using a similar protocol as investigators reported .~Aim 1: To demonstrate, in vitro, the relative cellular anti-hepatocellular cancer CSC immunity induced by hepatocellular cancer CSC-DC primed cytotoxic T cells.~Aim 2: To determine, in vitro, specific binding and lysis of hepatocellular cancer CSCs by antibodies produced by purified B cells from PBMCs stimulated with hepatocellular cancer CSC-DC.
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Study of Cancer Stem Cell Vcccinie That as a Specific Antigen in Metastatic Adenocarcinoma of the Liver
|
Neoplasms, Liver
|
* Biological: cancer stem cell vaccine
|
Inclusion Criteria:~Any patients with a diagnosis of HCC based on histology or the current accepted radiological measures.~Age > 18 years.~Patient has an MRI or CT result (positive for HCC) up to 3 months prior to recruitment.~AFP >30.~Patient who is not eligible for or failed any HCC treatment.~Karnofsky performance status >70%.~The patient shows normal organ function according to the following parameters(as measured within six weeks prior to treatment allocation):~Hemoglobin: Within normal range according to institutional standards; Absolute leukocyte count: Within normal range according to institutional standards; Absolute lymphocyte count: Within normal range according to institutional standards; Platelet count: Within normal range according to institutional standards; Alanine aminotransferase: ≤ 2.5 x Upper Limit of Normal (ULN); Aspartate aminotransferase: ≤ 2.5 x ULN; Total bilirubin: ≤ 1.5 x ULN. In the case of known Gilbert's syndrome ≤ 2 x ULN; Serum creatinine: 1.5 x ULN; Calculated creatinine clearance: > 50 mL/min .~No history of autoimmune diseases.~Ability to understand the study protocol and a willingness to sign a written informed consent document.~Exclusion Criteria:~Patients receiving anticoagulation therapy.~Patients who have received prior gemcitabine or radiation therapy to the liver bed.~Patients receiving any other investigational agents.~Patients with known brain metastases will be excluded because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse effects.~Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.~Patients who test positive for Hepatitis B virus, Hepatitis C virus or HIV. 7. level 3 hypertension; 8. severe coronary disease; 9. myelosuppression; 10. respiratory disease; 11. brain metastasis; 12. chronic infections
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of participants with adverse events | | up to 3 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary objectives are to evaluate vaccine immune responses to the immunizations by the data of body measurements | | 1 month |
|
Liver Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Neoplasms, Digestive System Diseases, Liver Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: non-cancer stem cell vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |
| Experimental: giving low dose vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |
| Experimental: giving middle dose vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |
| Experimental: giving high dose vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |
|
Cancer Stem Cells Vaccine Therapy in Treating Hepatocellular Cancer Patients
Study Overview
=================
Brief Summary
-----------------
Most studies of cancer stem cells (CSC) involve the inoculation of cells from human tumors into immunosuppressed mice, preventing an assessment on the immunologic interactions and effects of CSCs. In this study, the investigators examined the vaccination effects produced by CSC-enriched populations from histologically distinct murine tumors after their inoculation into different syngeneic immunocompetent hosts. Enriched CSCs were immunogenic and more effective as an antigen source than unselected tumor cells in inducing protective antitumor immunity.Immune sera from CSC-vaccinated hosts contained high levels of IgG which bound to CSCs, resulting in CSC lysis in the presence of complement.CTLs generated from peripheral blood mononuclear cells or splenocytes harvested from CSC-vaccinated hosts were capable of killing CSCs in vitro. Mechanistic investigations established that CSC-primed antibodies and T cells were capable of selective targeting CSCs and conferring anti-tumor immunity.
Detailed Description
-----------------
To assess the feasibility of generating CSC-loaded DC vaccines for clinical use, the investigators will harvest peripheral blood and tumor specimen from patients with hepatocellular cancer. The investigators will purify T, B cells and generate DCs from the PBMCs of the hepatocellular cancer patient.On the other hand, investigators will isolate ALDHhigh and ALDHlow tumor cells from the tumor specimen of the hepatocellular cancer patient using a similar protocol as investigators reported . Aim 1: To demonstrate, in vitro, the relative cellular anti-hepatocellular cancer CSC immunity induced by hepatocellular cancer CSC-DC primed cytotoxic T cells. Aim 2: To determine, in vitro, specific binding and lysis of hepatocellular cancer CSCs by antibodies produced by purified B cells from PBMCs stimulated with hepatocellular cancer CSC-DC.
Official Title
-----------------
Study of Cancer Stem Cell Vcccinie That as a Specific Antigen in Metastatic Adenocarcinoma of the Liver
Conditions
-----------------
Neoplasms, Liver
Intervention / Treatment
-----------------
* Biological: cancer stem cell vaccine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Any patients with a diagnosis of HCC based on histology or the current accepted radiological measures. Age > 18 years. Patient has an MRI or CT result (positive for HCC) up to 3 months prior to recruitment. AFP >30. Patient who is not eligible for or failed any HCC treatment. Karnofsky performance status >70%. The patient shows normal organ function according to the following parameters(as measured within six weeks prior to treatment allocation): Hemoglobin: Within normal range according to institutional standards; Absolute leukocyte count: Within normal range according to institutional standards; Absolute lymphocyte count: Within normal range according to institutional standards; Platelet count: Within normal range according to institutional standards; Alanine aminotransferase: ≤ 2.5 x Upper Limit of Normal (ULN); Aspartate aminotransferase: ≤ 2.5 x ULN; Total bilirubin: ≤ 1.5 x ULN. In the case of known Gilbert's syndrome ≤ 2 x ULN; Serum creatinine: 1.5 x ULN; Calculated creatinine clearance: > 50 mL/min . No history of autoimmune diseases. Ability to understand the study protocol and a willingness to sign a written informed consent document. Exclusion Criteria: Patients receiving anticoagulation therapy. Patients who have received prior gemcitabine or radiation therapy to the liver bed. Patients receiving any other investigational agents. Patients with known brain metastases will be excluded because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse effects. Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements. Patients who test positive for Hepatitis B virus, Hepatitis C virus or HIV. 7. level 3 hypertension; 8. severe coronary disease; 9. myelosuppression; 10. respiratory disease; 11. brain metastasis; 12. chronic infections
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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: non-cancer stem cell vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |
| Experimental: giving low dose vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |
| Experimental: giving middle dose vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |
| Experimental: giving high dose vaccine<br>The using dosage,frequency and duration of cancer stem cell vaccine are still undetermined. | Biological: cancer stem cell vaccine<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of participants with adverse events | | up to 3 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary objectives are to evaluate vaccine immune responses to the immunizations by the data of body measurements | | 1 month |
|
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NCT03736226
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A Post-Approval, Single-Arm Study of the SYNERGY Stent System in China
|
A prospective, observational, single-arm, open-label, multicenter, post-approval study. To compile real-world clinical outcomes data for the SYNERGYTM MONORAILTM Everolimus-Eluting Platinum Chromium Coronary Stent System (SYNERGYTM Stent System) in real-world clinical practice in China.
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This prospective, open-label, multi-center study is designed to provide post-market surveillance information on the SYNERGY Stent System. The study will evaluate clinical outcomes of subjects receiving the SYNERGY™ stents over 5 years in a real world setting according to post approval requirements by China government.
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A Post-Approval, Single-Arm Study of the SYNERGYTM MONORAILTM Everolimus-Eluting Platinum Chromium Coronary Stent System in China
|
Cardiovascular Diseases
|
* Device: SYNERGYTM Stent System
|
Inclusion Criteria:~• Subject must be at least 18 years of age~Subject understands and provides written informed consent~Subject who is clinically indicated and will have an attempt of at least one SYNERGYTM stent OR Subject who is clinically indicated and was implanted with at least one SYNERGYTM stent~Subject is willing to comply with all protocol-required follow-up evaluation~Exclusion Criteria:~Exclusion criteria are not required in this study which is an all comers study.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE rate | endpoints will be assessed post stent implant | 12 months |
|
Cardiovascular Diseases
|
| Intervention/Treatment |
| --- |
|Device: SYNERGYTM Stent System|no intervention design in the study|
|
A Post-Approval, Single-Arm Study of the SYNERGY Stent System in China
Study Overview
=================
Brief Summary
-----------------
A prospective, observational, single-arm, open-label, multicenter, post-approval study. To compile real-world clinical outcomes data for the SYNERGYTM MONORAILTM Everolimus-Eluting Platinum Chromium Coronary Stent System (SYNERGYTM Stent System) in real-world clinical practice in China.
Detailed Description
-----------------
This prospective, open-label, multi-center study is designed to provide post-market surveillance information on the SYNERGY Stent System. The study will evaluate clinical outcomes of subjects receiving the SYNERGY™ stents over 5 years in a real world setting according to post approval requirements by China government.
Official Title
-----------------
A Post-Approval, Single-Arm Study of the SYNERGYTM MONORAILTM Everolimus-Eluting Platinum Chromium Coronary Stent System in China
Conditions
-----------------
Cardiovascular Diseases
Intervention / Treatment
-----------------
* Device: SYNERGYTM Stent System
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: • Subject must be at least 18 years of age Subject understands and provides written informed consent Subject who is clinically indicated and will have an attempt of at least one SYNERGYTM stent OR Subject who is clinically indicated and was implanted with at least one SYNERGYTM stent Subject is willing to comply with all protocol-required follow-up evaluation Exclusion Criteria: Exclusion criteria are not required in this study which is an all comers study.
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: SYNERGYTM Stent System|no intervention design in the study|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE rate | endpoints will be assessed post stent implant | 12 months |
|
|||
NCT05518903
|
An Investigational Scan (68Ga-FAPI-46 PET/CT) for the Imaging of Cancer-Associated Fibroblasts in Patients With Localized Pancreatic Ductal Adenocarcinoma
|
This phase II trial tests whether 68Ga-FAPI-46 positron emission tomography (PET)/computed tomography (CT) scan works to image cancer-associated fibroblasts (CAFs) in patients with pancreatic ductal adenocarcinoma (PDA) that has not spread to other parts of the body (localized). CAFs are a type of connective tissue cell that are found within or near cancerous tissue. Many CAFs express a protein called fibroblast activation protein (FAP) that are not found on healthy cells in large amounts. 68Ga-FAPI-46 is a radioactive chemical compound designed to circulate through the body and attach itself to FAP on PDA cells. A PET/CT scan is then used to detect the location of FAP lesions. PET scan is a procedure in which a small amount of radioactive glucose (sugar) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the glucose is taken up. Because cancer cells often take up more glucose than normal cells, the pictures can be used to find cancer cells in the body. CT scan is a procedure that uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create 3-dimensional (3-D) views of tissues and organs. Combining a PET scan with a CT scan can help make the image easier to interpret. PET/CT scans are hybrid scanners that combine both modalities into a single scan during the same examination. Giving 68Ga-FAPI-46 PET/CT may help doctors improve upon the diagnosis and management of PDA.
|
PRIMARY OBJECTIVES:~I. To determine the sensitivity and specificity of gallium Ga 68 FAPi-46 (68Ga-FAPI-46) PET for detection and quantification of cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDA).~II. Construct, test and validate a model of surgical benefit or futility in potentially resectable PDA using 68Ga-FAPI-46 PET biomarkers in combination with other biomarkers of disease.~OUTLINE:~Patients receive 68Ga-FAP-46 intravenously (IV), then allow 60 minutes for 68Ga-FAPI-46 uptake. Patients then undergo PET/CT scans over 30 minutes at baseline (before standard of care [SOC] therapy), up to 2 scans approximately 8 weeks apart (at SOC re-staging visits), and a then a scan within 4 weeks of SOC surgical resection, if applicable.~After completion of study treatment, patients are followed up for 5 years.
|
Quantitative In Vivo 68Ga-Fibroblast-Activation-Protein-Inhibitors (FAPI)-46 PET Imaging of Cancer-Associated Fibroblasts (CAFs) in Pancreatic Ductal Adenocarcinoma (PDA)
|
Localized Pancreatic Adenocarcinoma, Resectable Pancreatic Ductal Adenocarcinoma, Stage 0 Pancreatic Cancer AJCC v8, Stage I Pancreatic Cancer AJCC v8, Stage IIA Pancreatic Cancer AJCC v8
|
* Procedure: Computed Tomography
* Drug: Gallium Ga 68 FAPi-46
* Procedure: Positron Emission Tomography
|
Inclusion Criteria:~Adults > 18 years (yrs.) with treatment-naive biopsy-proven PDA or with findings diagnostic for PDA on baseline imaging (CT, MRI, or PET)~Localized disease expected to undergo surgical resection following neoadjuvant therapy (NAT)~Eastern Cooperative Oncology Group (ECOG) performance status of 0-2~Ability to provide informed consent~Exclusion Criteria:~Hypersensitivity to any excipients in 68Ga-FAPI-46~Require emergency surgery~Non-PDA histology on biopsy~Histopathologically proven metastatic PDA~Pregnant or lactating women
|
18 Years
| null |
All
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic performance of fibroblast-activation-protein-inhibitors (FAPI) positron emission tomography (PET) for detection and quantification of cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDA) | Using surgical immunohistochemistry (IHC) as gold standard. | Up to 5 years |
| Relationship between 68Ga-FAPI-46 PET metrics in PDA | Relationship between 68Ga-FAPI-46 PET metrics assessed | Up to 5 years |
| Relationship between 68Ga-FAPI-46 PET metrics and cancer antigen 19-9 (CA19-9) biomarkers in PDA | Relationship between 68Ga-FAPI-46 PET metrics and cancer antigen 19-9 (CA19-9) being assessed. | Up to 5 years |
| Relationship between 68Ga-FAPI-46 PET metrics and Kirsten rat sarcoma (KRAS), circulating tumor deoxyribonucleic acid (ctDNA) biomarkers in PDA | Relationship between 68Ga-FAPI-46 PET metrics and Kirsten rat sarcoma (KRAS), circulating tumor deoxyribonucleic acid (ctDNA) being assessed. | Up to 5 years |
| Relationship between 68Ga-FAPI-46 PET metrics and staging examinations in PDA | Relationship between 68Ga-FAPI-46 PET metrics and fludeoxyglucose F-18 (FDG) PET staging exam being assessed. | Up to 5 years |
| Relationship between 68Ga-FAPI-46 PET metrics and staging examinations in PDA | Relationship between 68Ga-FAPI-46 PET metrics and magnetic resonance imaging (MRI) staging exam being assessed. | Up to 5 years |
|
FAPI-46, Radiopharmaceuticals, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (gallium GA 68 FAPi-46, PET/CT)<br>Patients receive 68Ga-FAP-46 IV, then allow 60 minutes for 68Ga-FAPI-46 uptake. Patients then undergo PET/CT scans over 30 minutes at baseline (before SOC therapy), up to 2 scans approximately 8 weeks apart (at SOC re-staging visits), and a then a scan within 4 weeks of SOC surgical resection, if applicable. | Procedure: Computed Tomography<br>* Undergo CT<br>* Other names: tomography;Drug: Gallium Ga 68 FAPi-46<br>* Given IV<br>* Other names: Gallium-68-FAPi-46;Procedure: Positron Emission Tomography<br>* Undergo PET<br>* Other names: PT;|
|
An Investigational Scan (68Ga-FAPI-46 PET/CT) for the Imaging of Cancer-Associated Fibroblasts in Patients With Localized Pancreatic Ductal Adenocarcinoma
Study Overview
=================
Brief Summary
-----------------
This phase II trial tests whether 68Ga-FAPI-46 positron emission tomography (PET)/computed tomography (CT) scan works to image cancer-associated fibroblasts (CAFs) in patients with pancreatic ductal adenocarcinoma (PDA) that has not spread to other parts of the body (localized). CAFs are a type of connective tissue cell that are found within or near cancerous tissue. Many CAFs express a protein called fibroblast activation protein (FAP) that are not found on healthy cells in large amounts. 68Ga-FAPI-46 is a radioactive chemical compound designed to circulate through the body and attach itself to FAP on PDA cells. A PET/CT scan is then used to detect the location of FAP lesions. PET scan is a procedure in which a small amount of radioactive glucose (sugar) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the glucose is taken up. Because cancer cells often take up more glucose than normal cells, the pictures can be used to find cancer cells in the body. CT scan is a procedure that uses a computer linked to an x-ray machine to make a series of detailed pictures of areas inside the body. The pictures are taken from different angles and are used to create 3-dimensional (3-D) views of tissues and organs. Combining a PET scan with a CT scan can help make the image easier to interpret. PET/CT scans are hybrid scanners that combine both modalities into a single scan during the same examination. Giving 68Ga-FAPI-46 PET/CT may help doctors improve upon the diagnosis and management of PDA.
Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To determine the sensitivity and specificity of gallium Ga 68 FAPi-46 (68Ga-FAPI-46) PET for detection and quantification of cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDA). II. Construct, test and validate a model of surgical benefit or futility in potentially resectable PDA using 68Ga-FAPI-46 PET biomarkers in combination with other biomarkers of disease. OUTLINE: Patients receive 68Ga-FAP-46 intravenously (IV), then allow 60 minutes for 68Ga-FAPI-46 uptake. Patients then undergo PET/CT scans over 30 minutes at baseline (before standard of care [SOC] therapy), up to 2 scans approximately 8 weeks apart (at SOC re-staging visits), and a then a scan within 4 weeks of SOC surgical resection, if applicable. After completion of study treatment, patients are followed up for 5 years.
Official Title
-----------------
Quantitative In Vivo 68Ga-Fibroblast-Activation-Protein-Inhibitors (FAPI)-46 PET Imaging of Cancer-Associated Fibroblasts (CAFs) in Pancreatic Ductal Adenocarcinoma (PDA)
Conditions
-----------------
Localized Pancreatic Adenocarcinoma, Resectable Pancreatic Ductal Adenocarcinoma, Stage 0 Pancreatic Cancer AJCC v8, Stage I Pancreatic Cancer AJCC v8, Stage IIA Pancreatic Cancer AJCC v8
Intervention / Treatment
-----------------
* Procedure: Computed Tomography
* Drug: Gallium Ga 68 FAPi-46
* Procedure: Positron Emission Tomography
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults > 18 years (yrs.) with treatment-naive biopsy-proven PDA or with findings diagnostic for PDA on baseline imaging (CT, MRI, or PET) Localized disease expected to undergo surgical resection following neoadjuvant therapy (NAT) Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Ability to provide informed consent Exclusion Criteria: Hypersensitivity to any excipients in 68Ga-FAPI-46 Require emergency surgery Non-PDA histology on biopsy Histopathologically proven metastatic PDA Pregnant or lactating 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?
-----------------
Design Details
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (gallium GA 68 FAPi-46, PET/CT)<br>Patients receive 68Ga-FAP-46 IV, then allow 60 minutes for 68Ga-FAPI-46 uptake. Patients then undergo PET/CT scans over 30 minutes at baseline (before SOC therapy), up to 2 scans approximately 8 weeks apart (at SOC re-staging visits), and a then a scan within 4 weeks of SOC surgical resection, if applicable. | Procedure: Computed Tomography<br>* Undergo CT<br>* Other names: tomography;Drug: Gallium Ga 68 FAPi-46<br>* Given IV<br>* Other names: Gallium-68-FAPi-46;Procedure: Positron Emission Tomography<br>* Undergo PET<br>* Other names: PT;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic performance of fibroblast-activation-protein-inhibitors (FAPI) positron emission tomography (PET) for detection and quantification of cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma (PDA) | Using surgical immunohistochemistry (IHC) as gold standard. | Up to 5 years |
| Relationship between 68Ga-FAPI-46 PET metrics in PDA | Relationship between 68Ga-FAPI-46 PET metrics assessed | Up to 5 years |
| Relationship between 68Ga-FAPI-46 PET metrics and cancer antigen 19-9 (CA19-9) biomarkers in PDA | Relationship between 68Ga-FAPI-46 PET metrics and cancer antigen 19-9 (CA19-9) being assessed. | Up to 5 years |
| Relationship between 68Ga-FAPI-46 PET metrics and Kirsten rat sarcoma (KRAS), circulating tumor deoxyribonucleic acid (ctDNA) biomarkers in PDA | Relationship between 68Ga-FAPI-46 PET metrics and Kirsten rat sarcoma (KRAS), circulating tumor deoxyribonucleic acid (ctDNA) being assessed. | Up to 5 years |
| Relationship between 68Ga-FAPI-46 PET metrics and staging examinations in PDA | Relationship between 68Ga-FAPI-46 PET metrics and fludeoxyglucose F-18 (FDG) PET staging exam being assessed. | Up to 5 years |
| Relationship between 68Ga-FAPI-46 PET metrics and staging examinations in PDA | Relationship between 68Ga-FAPI-46 PET metrics and magnetic resonance imaging (MRI) staging exam being assessed. | Up to 5 years |
|
||
NCT01591577
|
Lapatinib With Temozolomide and Regional Radiation Therapy for Patients With Newly-Diagnosed Glioblastoma Multiforme
|
The purpose of this study is to test the safety and effects of a combination of a study drug, Lapatinib, plus the administration of standard radiation therapy and an FDA approved drug Temozolomide (chemotherapy agent) in patients with newly diagnozed glioblastoma Multiforme.Currently, only radiation therapy and Temozolomide chemotherapy are standard treatment for brain cancer.Lapatinib has not been FDA approved for use in brain tumors treatment. It has been approved to be used as a daily treatment with other chemotherapies by the FDA for the treatment of advanced breast cancer.~The purpose of this study is to find the answers to the following research questions:~Is Lapatinib given twice a week at higher dosages, with radiation therapy and Temozolomide, safe when given to patients with brain tumor?~What are the side effects of Lapatinib given twice a week at higher dosages when given with radiation therapy and Temozolomide and how often do they occur?~Can Lapatinib, radiation, and Temozolomide be effective in shrinking tumors when given to patients with brain tumors?~To determine whether the presence of genetic alterations specific proteins in the tumor samples can predict whether this study drug is effective on the tumor.
|
Phase II Trial of Pulse Dosing of Lapatinib in Combination With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly-Diagnosed Glioblastoma Multiforme
|
Newly Diagnosed Glioblastoma Multiforme
|
* Other: Lapatinib/Temozolomide/radiation
|
Inclusion Criteria:~Patients will be included in the study based on the following criteria:~Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM) or gliosarcoma (GS). This includes treatment-naïve patients with prior tissue diagnoses of lower grade gliomas that have been upgraded to GBM after repeat resection.~Patients must have available archived tissues of 20-30 unstained slides. If frozen tissues are available, at least 200mg would be preferred, but not mandatory for study eligibility.~Use of effective means of contraception (men and women) in subjects of child-bearing potential~Cranial MRI or contrast CT must have been performed within 21 days of study entry. The use of MRI rather than CT is preferred. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. If the surgical procedure was a resection, cranial MRI or contrast CT performed within 96 hours of resection is preferred but not required. If the surgical procedure was a biopsy only, a head CT within 96 hours of the biopsy is acceptable. Patients without measurable or assessable disease are eligible.~Patients must begin partial brain radiotherapy and temozolomide chemotherapy no sooner than 2 weeks and no later than 5 weeks from the surgery in which tissue was collected. Patients with GBM diagnosis from surgeries in which tissue was not collected will be eligible after repeat surgery performed to collect tissue, as long as no treatment has been initiated prior to surgery in which tissue was collected. In this case, initiation of treatment must begin within 2 to 5 weeks from the last surgery. Patients may have radiotherapy administered at outside facilities according to the specified guidelines (Appendix F). Radiotherapy must be given within 2 days of lapatinib initiation and by external beam to a partial brain field in daily fractions of 2.0 Gy, to a planned total dose to the tumor of 60.0 Gy in accordance with Appendix F. Stereotactic radiosurgery and brachytherapy will not be allowed.~Patients must be willing to forego other drug therapy against the tumor while being treated with pulse dosing of lapatinib and temozolomide and radiation and subsequently pulse dosing lapatinib and temozolomide.~All patients must sign an informed consent approved by the Institutional Review Board indicating that they are aware of the investigational nature of this study. Patients must sign an authorization for the release of their protected health information.~Patients must be > 18 years old, and with a life expectancy > 12 weeks.~Patients must have a Karnofsky performance status of > 60.~Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl) and the test must be performed within 14 days prior to treatment initiation. Eligibility level for hemoglobin may be reached by transfusion.~Patients must have adequate liver function (AST, ALT < 2.5 times ULN, and bilirubin < 1.5 times ULN) and the test must be performed within 14 days prior to treatment initiation.~Patients must have adequate renal function (creatinine < 1.5 mg/dL) before starting therapy and the test must be performed within 14 days prior to treatment initiation.~EXCLUSION CRITERIA~Patients who received previous radiotherapy to the brain.~Patients who received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor. Patients who received Gliadel wafers will be excluded. Patients may have received or be receiving corticosteroids, analgesics, and other drugs to treat symptoms or prevent complications.~Patients who may be receiving any EIAED (see Appendix C) within 2 weeks prior to registration, or any other prohibited medications within the Washout Period per Appendix D prior to registration. See section 6.5 for seizure medication managements.~Patients with any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.~Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.~Women who are pregnant (determined by high titer of serum beta-HCG) or Breast-feeding. (Women with reproductive potential must practice adequate contraception.)~Patients who have any disease that will obscure toxicity or dangerously alter drug metabolism.~Patients who have serious uncontrolled inter-current medical illness including, but not limited to, ongoing or active infection requiring IV antibiotics and psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state (HIV, SLE, etc.).~Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The primary objective is to estimate the overall survival in subjects with newly-diagnosed glioblastoma treated with lapatinib/temozolomide/radiation followed by lapatinib/temozolomide for 2 years or until progression is detected. If no progression is seen at 2 years, then single-agent lapatinib will be continued until progression. | 2 years |
|
Temozolomide, Lapatinib, Antineoplastic Agents, Alkylating, Alkylating Agents, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Protein Kinase Inhibitors, Enzyme Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lapatinib/Temozolomide/radiation<br>Patients will be treated with a pulse dose of lapatinib every week and temozolomide 75 mg/m2 daily during radiation. Lapatinib will be administered beginning on the first day of radiation and temozolomide (+/-2 days). External beam fractionated regional radiation will be given on consecutive week days at 200 cGy daily doses to a total dose of 6000 cGy. Patients will have rest from temozolomide only for 2-4 weeks. Patients will continue with weekly pulse-dosing of lapatinib. After a 2-4 weeks rest(for temozolomide only) following completion of radiation therapy, temozolomide will be restarted as Cycle 1 at 150 mg/m2/day for 5 days out of every 28.Subsequent cycles can increase to 200 mg/m2/day as tolerated per investigator's judgment. Lapatinib pulse doses will be continued every week without interruption.Treatment will continue for 24 additional 28-day cycles of temozolomide if there is no evidence of progression. | Other: Lapatinib/Temozolomide/radiation<br>* Patients will be treated with a pulse dose of lapatinib every week and temozolomide 75 mg/m2 daily during radiation. Lapatinib will be administered beginning on the first day of radiation and temozolomide (+/-2 days). External beam fractionated regional radiation will be given on consecutive week days at 200 cGy daily doses to a total dose of 6000 cGy. Patients will have rest from temozolomide only for 2-4 weeks. Patients will continue with weekly pulse-dosing of lapatinib. After a 2-4 weeks rest(for temozolomide only) following completion of radiation therapy, temozolomide will be restarted as Cycle 1 at 150 mg/m2/day for 5 days out of every 28.Subsequent cycles can increase to 200 mg/m2/day as tolerated per investigator's judgment. Lapatinib pulse doses will be continued every week without interruption.Treatment will continue for 24 additional 28-day cycles of temozolomide if there is no evidence of progression.<br>|
|
Lapatinib With Temozolomide and Regional Radiation Therapy for Patients With Newly-Diagnosed Glioblastoma Multiforme
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test the safety and effects of a combination of a study drug, Lapatinib, plus the administration of standard radiation therapy and an FDA approved drug Temozolomide (chemotherapy agent) in patients with newly diagnozed glioblastoma Multiforme.Currently, only radiation therapy and Temozolomide chemotherapy are standard treatment for brain cancer.Lapatinib has not been FDA approved for use in brain tumors treatment. It has been approved to be used as a daily treatment with other chemotherapies by the FDA for the treatment of advanced breast cancer. The purpose of this study is to find the answers to the following research questions: Is Lapatinib given twice a week at higher dosages, with radiation therapy and Temozolomide, safe when given to patients with brain tumor? What are the side effects of Lapatinib given twice a week at higher dosages when given with radiation therapy and Temozolomide and how often do they occur? Can Lapatinib, radiation, and Temozolomide be effective in shrinking tumors when given to patients with brain tumors? To determine whether the presence of genetic alterations specific proteins in the tumor samples can predict whether this study drug is effective on the tumor.
Official Title
-----------------
Phase II Trial of Pulse Dosing of Lapatinib in Combination With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly-Diagnosed Glioblastoma Multiforme
Conditions
-----------------
Newly Diagnosed Glioblastoma Multiforme
Intervention / Treatment
-----------------
* Other: Lapatinib/Temozolomide/radiation
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients will be included in the study based on the following criteria: Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM) or gliosarcoma (GS). This includes treatment-naïve patients with prior tissue diagnoses of lower grade gliomas that have been upgraded to GBM after repeat resection. Patients must have available archived tissues of 20-30 unstained slides. If frozen tissues are available, at least 200mg would be preferred, but not mandatory for study eligibility. Use of effective means of contraception (men and women) in subjects of child-bearing potential Cranial MRI or contrast CT must have been performed within 21 days of study entry. The use of MRI rather than CT is preferred. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. If the surgical procedure was a resection, cranial MRI or contrast CT performed within 96 hours of resection is preferred but not required. If the surgical procedure was a biopsy only, a head CT within 96 hours of the biopsy is acceptable. Patients without measurable or assessable disease are eligible. Patients must begin partial brain radiotherapy and temozolomide chemotherapy no sooner than 2 weeks and no later than 5 weeks from the surgery in which tissue was collected. Patients with GBM diagnosis from surgeries in which tissue was not collected will be eligible after repeat surgery performed to collect tissue, as long as no treatment has been initiated prior to surgery in which tissue was collected. In this case, initiation of treatment must begin within 2 to 5 weeks from the last surgery. Patients may have radiotherapy administered at outside facilities according to the specified guidelines (Appendix F). Radiotherapy must be given within 2 days of lapatinib initiation and by external beam to a partial brain field in daily fractions of 2.0 Gy, to a planned total dose to the tumor of 60.0 Gy in accordance with Appendix F. Stereotactic radiosurgery and brachytherapy will not be allowed. Patients must be willing to forego other drug therapy against the tumor while being treated with pulse dosing of lapatinib and temozolomide and radiation and subsequently pulse dosing lapatinib and temozolomide. All patients must sign an informed consent approved by the Institutional Review Board indicating that they are aware of the investigational nature of this study. Patients must sign an authorization for the release of their protected health information. Patients must be > 18 years old, and with a life expectancy > 12 weeks. Patients must have a Karnofsky performance status of > 60. Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl) and the test must be performed within 14 days prior to treatment initiation. Eligibility level for hemoglobin may be reached by transfusion. Patients must have adequate liver function (AST, ALT < 2.5 times ULN, and bilirubin < 1.5 times ULN) and the test must be performed within 14 days prior to treatment initiation. Patients must have adequate renal function (creatinine < 1.5 mg/dL) before starting therapy and the test must be performed within 14 days prior to treatment initiation. EXCLUSION CRITERIA Patients who received previous radiotherapy to the brain. Patients who received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor. Patients who received Gliadel wafers will be excluded. Patients may have received or be receiving corticosteroids, analgesics, and other drugs to treat symptoms or prevent complications. Patients who may be receiving any EIAED (see Appendix C) within 2 weeks prior to registration, or any other prohibited medications within the Washout Period per Appendix D prior to registration. See section 6.5 for seizure medication managements. Patients with any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy. Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible. Women who are pregnant (determined by high titer of serum beta-HCG) or Breast-feeding. (Women with reproductive potential must practice adequate contraception.) Patients who have any disease that will obscure toxicity or dangerously alter drug metabolism. Patients who have serious uncontrolled inter-current medical illness including, but not limited to, ongoing or active infection requiring IV antibiotics and psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state (HIV, SLE, etc.). Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
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: Lapatinib/Temozolomide/radiation<br>Patients will be treated with a pulse dose of lapatinib every week and temozolomide 75 mg/m2 daily during radiation. Lapatinib will be administered beginning on the first day of radiation and temozolomide (+/-2 days). External beam fractionated regional radiation will be given on consecutive week days at 200 cGy daily doses to a total dose of 6000 cGy. Patients will have rest from temozolomide only for 2-4 weeks. Patients will continue with weekly pulse-dosing of lapatinib. After a 2-4 weeks rest(for temozolomide only) following completion of radiation therapy, temozolomide will be restarted as Cycle 1 at 150 mg/m2/day for 5 days out of every 28.Subsequent cycles can increase to 200 mg/m2/day as tolerated per investigator's judgment. Lapatinib pulse doses will be continued every week without interruption.Treatment will continue for 24 additional 28-day cycles of temozolomide if there is no evidence of progression. | Other: Lapatinib/Temozolomide/radiation<br>* Patients will be treated with a pulse dose of lapatinib every week and temozolomide 75 mg/m2 daily during radiation. Lapatinib will be administered beginning on the first day of radiation and temozolomide (+/-2 days). External beam fractionated regional radiation will be given on consecutive week days at 200 cGy daily doses to a total dose of 6000 cGy. Patients will have rest from temozolomide only for 2-4 weeks. Patients will continue with weekly pulse-dosing of lapatinib. After a 2-4 weeks rest(for temozolomide only) following completion of radiation therapy, temozolomide will be restarted as Cycle 1 at 150 mg/m2/day for 5 days out of every 28.Subsequent cycles can increase to 200 mg/m2/day as tolerated per investigator's judgment. Lapatinib pulse doses will be continued every week without interruption.Treatment will continue for 24 additional 28-day cycles of temozolomide if there is no evidence of progression.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The primary objective is to estimate the overall survival in subjects with newly-diagnosed glioblastoma treated with lapatinib/temozolomide/radiation followed by lapatinib/temozolomide for 2 years or until progression is detected. If no progression is seen at 2 years, then single-agent lapatinib will be continued until progression. | 2 years |
|
|||
NCT04720833
|
Effect of Dried Plum on Bone and Markers of Bone Status in Men
|
The principal objective of this study is to examine whether the addition of 100 g dried plum to the diets of men, regardless of their bone status, positively influences their indices of bone turnover in comparison with their corresponding baseline values and the control regimen.
|
To test the bone protective properties of dried plum, 66 men (50 to 79 years of age) will receive either 100 g dried plum/day or a control regimen for 12 months. Both groups will receive 500 mg calcium and 400 IU vitamin D daily.~Evaluation will be based on analyses of bone mineral density at baseline, 6 and 12-months and serum and urine markers of bone formation and resorption at baseline and 3, 6, and 12-months.
|
Effect of Dried Plum on Bone and Markers of Bone Status in Men
|
Osteoporosis, Osteopenia
|
* Dietary Supplement: dried plum
* Dietary Supplement: Calcium and vitamin D
|
Inclusion Criteria:~Healthy men (50-79 year-old)~Exclusion Criteria:~endocrine (e.g., prednisone, other glucocorticoids) or neuroactive (e.g., dilantin, phenobarbital) drugs or any drugs known to influence bone and calcium metabolism~Men whose BMD t-score at any site falls below 2.5 SD of the mean will be excluded from the study and referred to their primary care physician~subjects treated with calcitonin, bisphosphonates, raloxifene, sodium fluoride, anabolic agents, e.g. PTH and growth hormone, or steroids for less than 3 months prior to the start of the study will be excluded.~body mass index (BMI) <18 and >30 will be excluded to avoid extremes in leanness/adiposity and to readily allow body composition assessment.~If subjects smoke 20 cigarettes or more per day, they will be excluded.~Men who regularly consume dried plum or prune juice will not be accepted into the study.
|
50 Years
|
79 Years
|
Male
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomly assign to one of the arms.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone biomarkers | TRAP5b, BAP, CTX, P1NP | changes from baseline to 3 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density | BMD by DXA | changes from baseline to 12 months |
|
Prunes, dried plum, nutrition, bone
|
Vitamin D, Calcium, Vitamins, Micronutrients, Physiological Effects of Drugs, Calcium-Regulating Hormones and Agents, Bone Density Conservation Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dried plum (100 g dried plum)<br>Participants will receive 100 g dried plum daily plus 500 mg calcium and 300 IU vitamin D daily | Dietary Supplement: dried plum<br>* Dried plum<br>|
| Placebo Comparator: Calcium and vitamin D<br>Participants will receive 500 mg calcium and 300 IU vitamin D daily | Dietary Supplement: Calcium and vitamin D<br>* Calcium and vitamin D supplement<br>|
|
Effect of Dried Plum on Bone and Markers of Bone Status in Men
Study Overview
=================
Brief Summary
-----------------
The principal objective of this study is to examine whether the addition of 100 g dried plum to the diets of men, regardless of their bone status, positively influences their indices of bone turnover in comparison with their corresponding baseline values and the control regimen.
Detailed Description
-----------------
To test the bone protective properties of dried plum, 66 men (50 to 79 years of age) will receive either 100 g dried plum/day or a control regimen for 12 months. Both groups will receive 500 mg calcium and 400 IU vitamin D daily. Evaluation will be based on analyses of bone mineral density at baseline, 6 and 12-months and serum and urine markers of bone formation and resorption at baseline and 3, 6, and 12-months.
Official Title
-----------------
Effect of Dried Plum on Bone and Markers of Bone Status in Men
Conditions
-----------------
Osteoporosis, Osteopenia
Intervention / Treatment
-----------------
* Dietary Supplement: dried plum
* Dietary Supplement: Calcium and vitamin D
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy men (50-79 year-old) Exclusion Criteria: endocrine (e.g., prednisone, other glucocorticoids) or neuroactive (e.g., dilantin, phenobarbital) drugs or any drugs known to influence bone and calcium metabolism Men whose BMD t-score at any site falls below 2.5 SD of the mean will be excluded from the study and referred to their primary care physician subjects treated with calcitonin, bisphosphonates, raloxifene, sodium fluoride, anabolic agents, e.g. PTH and growth hormone, or steroids for less than 3 months prior to the start of the study will be excluded. body mass index (BMI) <18 and >30 will be excluded to avoid extremes in leanness/adiposity and to readily allow body composition assessment. If subjects smoke 20 cigarettes or more per day, they will be excluded. Men who regularly consume dried plum or prune juice will not be accepted into the study.
Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 79 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomly assign to one of the arms.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dried plum (100 g dried plum)<br>Participants will receive 100 g dried plum daily plus 500 mg calcium and 300 IU vitamin D daily | Dietary Supplement: dried plum<br>* Dried plum<br>|
| Placebo Comparator: Calcium and vitamin D<br>Participants will receive 500 mg calcium and 300 IU vitamin D daily | Dietary Supplement: Calcium and vitamin D<br>* Calcium and vitamin D supplement<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone biomarkers | TRAP5b, BAP, CTX, P1NP | changes from baseline to 3 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density | BMD by DXA | changes from baseline to 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prunes, dried plum, nutrition, bone
|
NCT04157153
|
First in Men Study: BIOMAG-I
|
A prospective, multi-center, first-in-man trial. Up to 115 subjects will be enrolled.
|
Clinical follow-up visits will take place at 1, 6, and 12 months and annually thereafter until 60 months post procedure.~All subjects will undergo an angiographic follow-up at 6- and 12-month follow up.~IVUS, (including IVUS-VH documentation) and OCT will be performed for all subjects at 6-month and 12-month follow-up (if the safety of the subject allows it and as per the investigator's decision).~Vasomotion will be assessed angiographically with Acetylcholine followed by Nitroglycerine at 12 months follow up in a subgroup of subjects, upon the investigators discretion and if subject consents.
|
BIOTRONIK - Safety and Clinical Performance of the - Sirolimus-Eluting Resorbable Coronary Magnesium Scaffold System (DREAMS 3G) in the Treatment of Subjects With de Novo Lesions in Native Coronary Arteries
|
Coronary Artery Disease
|
* Device: Implantation of a Sirolimus-Eluting Resorbable Coronary Magnesium Scaffold
|
Inclusion Criteria:~Subject is > 18 years and < 80 years of age~Written subject informed consent available prior to PCI~Subject eligible for PCI~Subjects with a maximum of two single lesions in two separate coronary arteries which have to be de novo lesions and can be covered with 1 device each~Reference vessel diameter between 2.5-4.2 mm by visual estimation, depending on the scaffold size used~Target lesion length ≤ 28 mm by visual estimation, depending on the scaffold size used~Target lesion stenosis by visual estimation > 50% - < 100% and TIMI flow ≥1 (assisted by e.g. QCA / IVUS /FFR).~Subjects with stable or unstable angina pectoris or documented silent ischemia or hemodynamically stable NSTEMI patients without angiographic evidence of thrombus at target lesion~Eligible for Dual Anti Platelet Therapy (DAPT)~Exclusion Criteria:~Pregnant or breast-feeding females or females who intend to become pregnant during the time of the study~Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute ST elevation myocardial infarction (STEMI) within 72 hours prior to the index procedure.~Left main coronary artery disease~Three-vessels with coronary artery disease requiring treatment at time of procedure~Planned interventional treatment of any non-target vessel within 12-month post-procedure~Subjects on dialysis~Planned intervention of the target vessel post index procedure~Ostial target lesion (within 5.0 mm of vessel origin)~Target lesion involves a side branch >2.0 mm in diameter~Documented left ventricular ejection fraction (LVEF) ≤ 30% within the last 6 months~Heavily calcified lesion~Target lesion is located in or supplied by an arterial or venous bypass graft~Target lesion requiring treatment with a device other than the non-compliant pre-dilatation balloon or scoring balloon prior to scaffold placement (including but not limited to rotational atherectomy, etc.)~Unsuccessful pre-dilatation, defined as a residual stenosis rate more than 20%, estimated by any method and/or angiographic complications (e.g. distal embolization, side branch closure, extensive dissections)~Known allergies to: Acetylsalicylic Acid (ASA), P2Y12 inhibitors, Heparin, Contrast medium, Sirolimus, or similar drugs; or the scaffold material~Subject is receiving an oral or intravenous immuno-suppressive therapy (e.g., inhaled steroids are not excluded) or has a known life-limiting immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematosus) diabetes mellitus is not excluded)~A stenosis located proximal or distal to the target lesion that might require future revascularization or an impede run off detected during diagnostic angiography~Life expectancy less than 1 year~Planned surgery or dental surgical procedure within 6 months after index procedure unless DAPT will be maintained~In the investigators opinion, subject will not be able to comply with the follow-up requirements~Subject is currently participating in another study with an investigational device or an investigational drug and has not reached the primary endpoint yet
|
18 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In scaffold late lumen loss | Independent Core Lab Assessment | At 6 months after index procedure |
|
Sirolimus, Anti-Bacterial Agents, Anti-Infective Agents, Antibiotics, Antineoplastic, Antineoplastic Agents, Antifungal Agents, Immunosuppressive Agents, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>All subjects will be implanted with the Sirolimus-Eluting Resorbable Coronary Magnesium Scaffold System (DREAMS 3G) and followed up until 60 months. | Device: Implantation of a Sirolimus-Eluting Resorbable Coronary Magnesium Scaffold<br>* Subjects with symptomatic coronary artery disease who qualify for percutaneous coronary intervention (PCI) will be treated with a sirolimus eluting resorbable coronary Magnesium scaffold<br>|
|
First in Men Study: BIOMAG-I
Study Overview
=================
Brief Summary
-----------------
A prospective, multi-center, first-in-man trial. Up to 115 subjects will be enrolled.
Detailed Description
-----------------
Clinical follow-up visits will take place at 1, 6, and 12 months and annually thereafter until 60 months post procedure. All subjects will undergo an angiographic follow-up at 6- and 12-month follow up. IVUS, (including IVUS-VH documentation) and OCT will be performed for all subjects at 6-month and 12-month follow-up (if the safety of the subject allows it and as per the investigator's decision). Vasomotion will be assessed angiographically with Acetylcholine followed by Nitroglycerine at 12 months follow up in a subgroup of subjects, upon the investigators discretion and if subject consents.
Official Title
-----------------
BIOTRONIK - Safety and Clinical Performance of the - Sirolimus-Eluting Resorbable Coronary Magnesium Scaffold System (DREAMS 3G) in the Treatment of Subjects With de Novo Lesions in Native Coronary Arteries
Conditions
-----------------
Coronary Artery Disease
Intervention / Treatment
-----------------
* Device: Implantation of a Sirolimus-Eluting Resorbable Coronary Magnesium Scaffold
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is > 18 years and < 80 years of age Written subject informed consent available prior to PCI Subject eligible for PCI Subjects with a maximum of two single lesions in two separate coronary arteries which have to be de novo lesions and can be covered with 1 device each Reference vessel diameter between 2.5-4.2 mm by visual estimation, depending on the scaffold size used Target lesion length ≤ 28 mm by visual estimation, depending on the scaffold size used Target lesion stenosis by visual estimation > 50% - < 100% and TIMI flow ≥1 (assisted by e.g. QCA / IVUS /FFR). Subjects with stable or unstable angina pectoris or documented silent ischemia or hemodynamically stable NSTEMI patients without angiographic evidence of thrombus at target lesion Eligible for Dual Anti Platelet Therapy (DAPT) Exclusion Criteria: Pregnant or breast-feeding females or females who intend to become pregnant during the time of the study Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute ST elevation myocardial infarction (STEMI) within 72 hours prior to the index procedure. Left main coronary artery disease Three-vessels with coronary artery disease requiring treatment at time of procedure Planned interventional treatment of any non-target vessel within 12-month post-procedure Subjects on dialysis Planned intervention of the target vessel post index procedure Ostial target lesion (within 5.0 mm of vessel origin) Target lesion involves a side branch >2.0 mm in diameter Documented left ventricular ejection fraction (LVEF) ≤ 30% within the last 6 months Heavily calcified lesion Target lesion is located in or supplied by an arterial or venous bypass graft Target lesion requiring treatment with a device other than the non-compliant pre-dilatation balloon or scoring balloon prior to scaffold placement (including but not limited to rotational atherectomy, etc.) Unsuccessful pre-dilatation, defined as a residual stenosis rate more than 20%, estimated by any method and/or angiographic complications (e.g. distal embolization, side branch closure, extensive dissections) Known allergies to: Acetylsalicylic Acid (ASA), P2Y12 inhibitors, Heparin, Contrast medium, Sirolimus, or similar drugs; or the scaffold material Subject is receiving an oral or intravenous immuno-suppressive therapy (e.g., inhaled steroids are not excluded) or has a known life-limiting immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematosus) diabetes mellitus is not excluded) A stenosis located proximal or distal to the target lesion that might require future revascularization or an impede run off detected during diagnostic angiography Life expectancy less than 1 year Planned surgery or dental surgical procedure within 6 months after index procedure unless DAPT will be maintained In the investigators opinion, subject will not be able to comply with the follow-up requirements Subject is currently participating in another study with an investigational device or an investigational drug and has not reached the primary endpoint yet
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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>All subjects will be implanted with the Sirolimus-Eluting Resorbable Coronary Magnesium Scaffold System (DREAMS 3G) and followed up until 60 months. | Device: Implantation of a Sirolimus-Eluting Resorbable Coronary Magnesium Scaffold<br>* Subjects with symptomatic coronary artery disease who qualify for percutaneous coronary intervention (PCI) will be treated with a sirolimus eluting resorbable coronary Magnesium scaffold<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In scaffold late lumen loss | Independent Core Lab Assessment | At 6 months after index procedure |
|
||
NCT04364074
|
Acute Probiotic Supplementation and Endothelial Function
|
One in every two deaths in the United States is caused by cardiovascular disease. Despite strong mechanistic links established between a diet rich in lipids and the pathogenesis of cardiovascular disease, therapeutic advances have focused on reduction in either ingestion or synthesis of cholesterol, and reduction in dietary trans and saturated fatty acids and triglycerides. Even in the setting of aggressive high potency statin therapy and global cardiovascular risk reduction efforts, most clinical trials reveal a significant residual cardiovascular risk with, at best, only 30% reduction in major adverse cardiovascular events. There exists a significant unmet clinical need for identifying novel therapies for the prevention and treatment of cardiovascular disease. This requires identification of additional contributory processes to cardiovascular disease pathogenesis, so that mechanism-based interventions may be developed. Endothelial dysfunction is a pathological state in which there is systemic inflammation of vascular endothelium with consequent expression of pro-vasoconstrictive mediators, thrombotic and atherogenic tendencies. Endothelial dysfunction precedes the development of atherosclerosis and portends an increased risk of future adverse cardiovascular events. Endothelial dysfunction, therefore, can serve as a barometer of future cardiovascular risk. Measurement of Flow-mediated dilation ( FMD) is widely accepted as a method to assess vascular endothelial function.
|
Researchers at MCW have discovered a new pathway that links the type of bacteria present in the intestines to the severity of heart attacks. This discovery of a relationship between intestinal bacteria, bacterial metabolites, and severity of heart attacks means that for the first time, we may be able to determine a person's probability of having a heart attack via non-conventional risk factors. This may provide opportunities for novel diagnostic tests as well as a potential for therapeutic intervention. The link between gut microbiota and the severity of heart attacks may also lead to novel therapeutic approaches (probiotics, non-absorbable antibiotics) to prevent heart attacks from happening. Our pilot study has demonstrated that supplementation of Lactobacillus plantarum 299v (Lp299v) for 6 weeks to adults with a history of coronary artery disease showed improvement in endothelial function. Whether acute ingestion of a single drink containing Lp299v supplementation favorably impacts vascular endothelial function is not known. The study proposed will test the hypothesis that supplementation of Lp299v favorably impacts vascular endothelial function after ingestion of a single supplement containing Lp299v.~Specific Aim 1 will determine the acute impact of probiotic supplementation on endothelial cell function as measured by brachial artery flow mediated dilation (FMD)~Specific Aim 2 will determine the impact of acute probiotic supplementation on blood biomarkers for inflammation.~Specific Aim 3 will be to determine the impact of baseline constitution of intestinal microbiota (assessed by stool microbiome) on change in FMD as a result of acute response to probiotic supplementation.~Specific Aim 4 will be to determine the impact of baseline constitution of intestinal microbiota (assessed by stool microbiome) on change in levels of blood markers for inflammation as a result of acute response probiotic supplementation.
|
Acute Impact of Probiotic Supplementation on Endothelial Function in Adults
|
Coronary Artery Disease, Hypertension, Hyperlipidemias, Peripheral Vascular Diseases, Cerebral Arterial Diseases
|
* Dietary Supplement: Goodbelly
* Dietary Supplement: Placebo
|
Inclusion Criteria:~Have at least one of the following conditions:~Hypertension~Hyperlipidemia~Diabetes mellitus (Type 1 or Type 2)~Peripheral vascular disease~Cerebrovascular disease~Cardiovascular disease.~Exclusion Criteria:~Unstable angina or myocardial infarction by history, ECG, and/or enzymatic criteria within 1 month of enrollment.~LV dysfunction as defined by an LV ejection fraction documented as < 45% within 1 year of enrollment by an echocardiogram, MRI, or nuclear imaging.~Uncontrolled hypertension with blood pressure greater than 170/100 mmHg at the screening visit.~Known history of chronic renal insufficiency, liver dysfunction, or cancer besides non-melanoma skin carcinomas or localized prostate cancer requiring systemic treatment within five years of enrollment.~Known history of cognitive impairment or inability to follow study procedures~Patient with an implanted defibrillator or permanent pacemaker on which the potential participant is known to rely upon for greater than 50% of ventricular depolarizations.~Patients who received probiotics, prebiotics, and antibiotics in the last 12 weeks.~Patients with dosing changes of vasoactive medications and HMG-CoA reductase inhibitors in the 6 weeks prior to enrollment.~Pregnancy~Patients who are currently taking Vitamin K antagonists such as coumadin, warfarin.~Those who are daily drinkers.~Patients with gastrointestinal diseases that might alter the impact of a probiotic (e.g. status post colectomy, short gut syndrome, or inflammatory bowel disease)
|
21 Years
|
89 Years
|
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in baseline flow mediated dilation (FMD) after probiotic consumption | This is a measurement of endothelial function in the brachial artery | from baseline to 24 hours after consumption and approximately 7 days after consumption |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukin-6 | Circulating marker of inflammation | from baseline to 24 hours after consumption and approximately 7 days after consumption |
| Interleukin-8 | Circulating marker of inflammation | from baseline to 24 hours after consumption and approximately 7 days after consumption |
| Interleukin-12 | Circulating marker of inflammation | from baseline to 24 hours after consumption and approximately 7 days after consumption |
|
Cerebral Arterial Diseases, Coronary Artery Disease, Vascular Diseases, Peripheral Vascular Diseases, Peripheral Arterial Disease, Hyperlipidemias, Cardiovascular Diseases, Coronary Disease, Myocardial Ischemia, Heart Diseases, Arteriosclerosis, Arterial Occlusive Diseases, Dyslipidemias, Lipid Metabolism Disorders, Metabolic Diseases, Atherosclerosis, Intracranial Arterial Diseases, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GoodBelly Probiotic<br>Subjects randomized to this arm consume one serving of the Goodbelly lactobacillus plantarum 299v probiotic | Dietary Supplement: Goodbelly<br>* Consumption of 1 serving of Goodbelly probiotic daily for 6 weeks. This will be followed by an observation period for 6 weeks during which the subjects will not consume Goodbelly.<br>* Other names: Goodbelly probiotic;|
| Placebo Comparator: Placebo<br>Subjects randomized to this arm consume one serving of the Goodbelly that does not contain lactobacillus plantarum 299v | Dietary Supplement: Placebo<br>* To prepare the placebo, the dietitian will first heat a water bath to 80 degrees Celsius. This removes the lactobacillus plantarum 299v from the probiotic drink<br>* Other names: Goodbelly Probitoic;|
|
Acute Probiotic Supplementation and Endothelial Function
Study Overview
=================
Brief Summary
-----------------
One in every two deaths in the United States is caused by cardiovascular disease. Despite strong mechanistic links established between a diet rich in lipids and the pathogenesis of cardiovascular disease, therapeutic advances have focused on reduction in either ingestion or synthesis of cholesterol, and reduction in dietary trans and saturated fatty acids and triglycerides. Even in the setting of aggressive high potency statin therapy and global cardiovascular risk reduction efforts, most clinical trials reveal a significant residual cardiovascular risk with, at best, only 30% reduction in major adverse cardiovascular events. There exists a significant unmet clinical need for identifying novel therapies for the prevention and treatment of cardiovascular disease. This requires identification of additional contributory processes to cardiovascular disease pathogenesis, so that mechanism-based interventions may be developed. Endothelial dysfunction is a pathological state in which there is systemic inflammation of vascular endothelium with consequent expression of pro-vasoconstrictive mediators, thrombotic and atherogenic tendencies. Endothelial dysfunction precedes the development of atherosclerosis and portends an increased risk of future adverse cardiovascular events. Endothelial dysfunction, therefore, can serve as a barometer of future cardiovascular risk. Measurement of Flow-mediated dilation ( FMD) is widely accepted as a method to assess vascular endothelial function.
Detailed Description
-----------------
Researchers at MCW have discovered a new pathway that links the type of bacteria present in the intestines to the severity of heart attacks. This discovery of a relationship between intestinal bacteria, bacterial metabolites, and severity of heart attacks means that for the first time, we may be able to determine a person's probability of having a heart attack via non-conventional risk factors. This may provide opportunities for novel diagnostic tests as well as a potential for therapeutic intervention. The link between gut microbiota and the severity of heart attacks may also lead to novel therapeutic approaches (probiotics, non-absorbable antibiotics) to prevent heart attacks from happening. Our pilot study has demonstrated that supplementation of Lactobacillus plantarum 299v (Lp299v) for 6 weeks to adults with a history of coronary artery disease showed improvement in endothelial function. Whether acute ingestion of a single drink containing Lp299v supplementation favorably impacts vascular endothelial function is not known. The study proposed will test the hypothesis that supplementation of Lp299v favorably impacts vascular endothelial function after ingestion of a single supplement containing Lp299v. Specific Aim 1 will determine the acute impact of probiotic supplementation on endothelial cell function as measured by brachial artery flow mediated dilation (FMD) Specific Aim 2 will determine the impact of acute probiotic supplementation on blood biomarkers for inflammation. Specific Aim 3 will be to determine the impact of baseline constitution of intestinal microbiota (assessed by stool microbiome) on change in FMD as a result of acute response to probiotic supplementation. Specific Aim 4 will be to determine the impact of baseline constitution of intestinal microbiota (assessed by stool microbiome) on change in levels of blood markers for inflammation as a result of acute response probiotic supplementation.
Official Title
-----------------
Acute Impact of Probiotic Supplementation on Endothelial Function in Adults
Conditions
-----------------
Coronary Artery Disease, Hypertension, Hyperlipidemias, Peripheral Vascular Diseases, Cerebral Arterial Diseases
Intervention / Treatment
-----------------
* Dietary Supplement: Goodbelly
* Dietary Supplement: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have at least one of the following conditions: Hypertension Hyperlipidemia Diabetes mellitus (Type 1 or Type 2) Peripheral vascular disease Cerebrovascular disease Cardiovascular disease. Exclusion Criteria: Unstable angina or myocardial infarction by history, ECG, and/or enzymatic criteria within 1 month of enrollment. LV dysfunction as defined by an LV ejection fraction documented as < 45% within 1 year of enrollment by an echocardiogram, MRI, or nuclear imaging. Uncontrolled hypertension with blood pressure greater than 170/100 mmHg at the screening visit. Known history of chronic renal insufficiency, liver dysfunction, or cancer besides non-melanoma skin carcinomas or localized prostate cancer requiring systemic treatment within five years of enrollment. Known history of cognitive impairment or inability to follow study procedures Patient with an implanted defibrillator or permanent pacemaker on which the potential participant is known to rely upon for greater than 50% of ventricular depolarizations. Patients who received probiotics, prebiotics, and antibiotics in the last 12 weeks. Patients with dosing changes of vasoactive medications and HMG-CoA reductase inhibitors in the 6 weeks prior to enrollment. Pregnancy Patients who are currently taking Vitamin K antagonists such as coumadin, warfarin. Those who are daily drinkers. Patients with gastrointestinal diseases that might alter the impact of a probiotic (e.g. status post colectomy, short gut syndrome, or inflammatory bowel disease)
Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 89 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: GoodBelly Probiotic<br>Subjects randomized to this arm consume one serving of the Goodbelly lactobacillus plantarum 299v probiotic | Dietary Supplement: Goodbelly<br>* Consumption of 1 serving of Goodbelly probiotic daily for 6 weeks. This will be followed by an observation period for 6 weeks during which the subjects will not consume Goodbelly.<br>* Other names: Goodbelly probiotic;|
| Placebo Comparator: Placebo<br>Subjects randomized to this arm consume one serving of the Goodbelly that does not contain lactobacillus plantarum 299v | Dietary Supplement: Placebo<br>* To prepare the placebo, the dietitian will first heat a water bath to 80 degrees Celsius. This removes the lactobacillus plantarum 299v from the probiotic drink<br>* Other names: Goodbelly Probitoic;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in baseline flow mediated dilation (FMD) after probiotic consumption | This is a measurement of endothelial function in the brachial artery | from baseline to 24 hours after consumption and approximately 7 days after consumption |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukin-6 | Circulating marker of inflammation | from baseline to 24 hours after consumption and approximately 7 days after consumption |
| Interleukin-8 | Circulating marker of inflammation | from baseline to 24 hours after consumption and approximately 7 days after consumption |
| Interleukin-12 | Circulating marker of inflammation | from baseline to 24 hours after consumption and approximately 7 days after consumption |
|
|
NCT00765869
|
Randomised Controlled Trial of a Literacy Sensitive Decision Aid for Bowel Cancer Screening
|
The purpose of this study is to evaluate a decision aid (written information booklet designed to facilitate informed decision making) to help people aged 55-64 years, with low levels of education and literacy, make an informed choice about bowel cancer screening, using faecal occult blood testing.
|
Several countries have recently implemented national bowel cancer screening programs. To ensure equal access to screening, consumer information is needed to suit adults ranging in literacy level. Decision aids (DAs) are tools which have been developed to assist patients and consumers make informed health decisions and encourage active participation in health care decisions. Their use in a wide range of clinical settings has increased dramatically. However, most DAs are highly dependent upon high levels of literacy and numeracy, and few have been developed for low literacy populations.~This primary aims of this study are to assess the impact of the decision aid on (1) the proportion of adults who make an informed choice about bowel cancer screening (using faecal occult blood test) and, (2) the level of involvement in screening decisions among adults with lower levels of education and literacy.~There are three secondary aims of the study. First, to measure the effect of the decision support tool on decisional conflict, decision satisfaction, anxiety, and bowel cancer worry. Second, to identify participant's screening interest, intentions and behavior. Thirdly, we will explore participant's reactions towards the information materials they receive and whether the doctor influenced their screening decision.
|
A Randomised Controlled Trial of a Bowel Cancer Screening Decision Aid for Adults With Low Education and Literacy
|
Colorectal Neoplasms
|
* Other: Bowel cancer screening decision aid
* Other: Bowel cancer screening decision aid
* Other: Australian Government Bowel Cancer Screening booklet
|
Inclusion Criteria:~Men and women aged 55-64 years~Lower levels of education~English as a main language spoken at home~Average risk of bowel cancer~Exclusion Criteria:~Higher levels of education~Invitation to take part in bowel cancer screening in last two years~Personal or strong family history of bowel cancer~Had a bowel cancer screening test in the last two years
|
55 Years
|
64 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Informed choice | | 2 weeks post intervention |
| Involvement in screening decision | | 2 weeks post intervention |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anxiety | | 2 weeks post intervention |
| Bowel cancer worry | | 2 weeks post intervention |
| Decisional conflict | | 2 weeks post intervention |
| Decision satisfaction | | 2 weeks post intervention |
| Bowel cancer screening interest | | 2 weeks post intervention |
| Bowel cancer screening intentions | | 2 weeks post intervention |
| Screening behaviour | | 2 weeks post intervention |
| Self reported bowel cancer symptoms | | 2 weeks post intervention |
| Evaluation of intervention materials | | 2 weeks post intervention |
| Influence of doctor on screening decision | | 2 weeks post intervention |
|
Decision support techniques
|
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: 1<br>Bowel cancer screening decision aid, DVD and Question Prompt List (QPL) | Other: Bowel cancer screening decision aid<br>* A decision aid developed for adults with low levels of education and literacy making decisions about bowel cancer screening, using faecal occult blood test (FOBT)<br>|
| Experimental: 2<br>Bowel cancer screening decision with DVD only | Other: Bowel cancer screening decision aid<br>* A decision aid developed for adults with low levels of education and literacy making decisions about bowel cancer screening, using faecal occult blood test (FOBT)<br>|
| Active Comparator: 3<br>Australian Government Bowel Cancer Screening consumer information booklet | Other: Australian Government Bowel Cancer Screening booklet<br>* A consumer booklet developed by the Australian Government for people taking part in the National Bowel Cancer Screening program<br>|
|
Randomised Controlled Trial of a Literacy Sensitive Decision Aid for Bowel Cancer Screening
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate a decision aid (written information booklet designed to facilitate informed decision making) to help people aged 55-64 years, with low levels of education and literacy, make an informed choice about bowel cancer screening, using faecal occult blood testing.
Detailed Description
-----------------
Several countries have recently implemented national bowel cancer screening programs. To ensure equal access to screening, consumer information is needed to suit adults ranging in literacy level. Decision aids (DAs) are tools which have been developed to assist patients and consumers make informed health decisions and encourage active participation in health care decisions. Their use in a wide range of clinical settings has increased dramatically. However, most DAs are highly dependent upon high levels of literacy and numeracy, and few have been developed for low literacy populations. This primary aims of this study are to assess the impact of the decision aid on (1) the proportion of adults who make an informed choice about bowel cancer screening (using faecal occult blood test) and, (2) the level of involvement in screening decisions among adults with lower levels of education and literacy. There are three secondary aims of the study. First, to measure the effect of the decision support tool on decisional conflict, decision satisfaction, anxiety, and bowel cancer worry. Second, to identify participant's screening interest, intentions and behavior. Thirdly, we will explore participant's reactions towards the information materials they receive and whether the doctor influenced their screening decision.
Official Title
-----------------
A Randomised Controlled Trial of a Bowel Cancer Screening Decision Aid for Adults With Low Education and Literacy
Conditions
-----------------
Colorectal Neoplasms
Intervention / Treatment
-----------------
* Other: Bowel cancer screening decision aid
* Other: Bowel cancer screening decision aid
* Other: Australian Government Bowel Cancer Screening booklet
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged 55-64 years Lower levels of education English as a main language spoken at home Average risk of bowel cancer Exclusion Criteria: Higher levels of education Invitation to take part in bowel cancer screening in last two years Personal or strong family history of bowel cancer Had a bowel cancer screening test in the last two years
Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 64 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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Bowel cancer screening decision aid, DVD and Question Prompt List (QPL) | Other: Bowel cancer screening decision aid<br>* A decision aid developed for adults with low levels of education and literacy making decisions about bowel cancer screening, using faecal occult blood test (FOBT)<br>|
| Experimental: 2<br>Bowel cancer screening decision with DVD only | Other: Bowel cancer screening decision aid<br>* A decision aid developed for adults with low levels of education and literacy making decisions about bowel cancer screening, using faecal occult blood test (FOBT)<br>|
| Active Comparator: 3<br>Australian Government Bowel Cancer Screening consumer information booklet | Other: Australian Government Bowel Cancer Screening booklet<br>* A consumer booklet developed by the Australian Government for people taking part in the National Bowel Cancer Screening program<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Informed choice | | 2 weeks post intervention |
| Involvement in screening decision | | 2 weeks post intervention |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anxiety | | 2 weeks post intervention |
| Bowel cancer worry | | 2 weeks post intervention |
| Decisional conflict | | 2 weeks post intervention |
| Decision satisfaction | | 2 weeks post intervention |
| Bowel cancer screening interest | | 2 weeks post intervention |
| Bowel cancer screening intentions | | 2 weeks post intervention |
| Screening behaviour | | 2 weeks post intervention |
| Self reported bowel cancer symptoms | | 2 weeks post intervention |
| Evaluation of intervention materials | | 2 weeks post intervention |
| Influence of doctor on screening decision | | 2 weeks post intervention |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Decision support techniques
|
NCT03190915
|
Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
|
This phase II trial studies how well trametinib works in treating patients with juvenile myelomonocytic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
|
PRIMARY OBJECTIVE:~I. To determine the objective response rate to trametinib in children with recurrent or refractory juvenile myelomonocytic leukemia (JMML).~SECONDARY OBJECTIVES:~I. To further define and describe the toxicities of single agent trametinib in children with recurrent or refractory JMML.~II. To further characterize the pharmacokinetics of trametinib in children with recurrent or refractory JMML.~III. To prospectively evaluate mutant allele burden as a marker of disease activity in JMML.~IV. To measure the rate of complete responses in children with recurrent or refractory JMML.~V. To measure the duration of response among responders.~EXPLORATORY OBJECTIVE:~I. To describe the distribution of JMML diagnostic criteria in children with recurrent or refractory JMML.~OUTLINE:~Patients receive trametinib orally (PO) once daily (QD) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a bone marrow aspiration or biopsy at baseline, on day 28 of cycles 1 and 2, at all subsequent odd numbered cycles, and at end of treatment.~After completion of study treatment, patients are followed up annually for up to 5 years.
|
A Phase 2 Study of the MEK Inhibitor Trametinib (NSC# 763093) in Children With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
|
Juvenile Myelomonocytic Leukemia, Neurofibromatosis Type 1
|
* Procedure: Bone Marrow Aspiration and Biopsy
* Drug: Trametinib
|
Inclusion Criteria:~Patients must be >= 1 month and < 22 years of age at the time of study entry~Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease; the diagnosis is made based on the following criteria~JMML category 1 (all of the following): the diagnostic criteria must include all features in category 1 and EITHER (i) one of the features in category 2 OR (ii) two features from category 3 to make the diagnosis~Splenomegaly~> 1000 (1 x 10^9/uL) circulating monocytes~< 20% blasts in the bone marrow or peripheral blood~Absence of the t(9;22) or BCR/ABL fusion gene~JMML category 2 (at least one of the following if at least two category 3 criteria are not present):~Somatic mutation in RAS or PTPN11~Clinical diagnosis of NF1 or NF1 gene mutation~Homozygous mutation in CBL~Monosomy 7~JMML category 3 (at least two of the following if no category 2 criteria are met):~Circulating myeloid precursors~White blood cell count, > 10 000 (10 x 10^9/ uL)~Increased hemoglobin F for age~Clonal cytogenetic abnormality~GM-CSF hypersensitivity~Patients with refractory or relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) demethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality; frontline therapy is defined as one cycle of intravenous chemotherapy that includes any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine; frontline therapy will also include any conditioning regimen as part of a stem cell transplant; patients who transform to AML at any point with more than 20% blasts are not eligible for this trial~Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score~Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment~Myelosuppressive chemotherapy: patients must have completely recovered from all acute toxic effects of chemotherapy, immunotherapy or radiotherapy prior to study enrollment; at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea~Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of protocol therapy~Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur~Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur~Monoclonal antibodies:~At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines~At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody~Radiotherapy:~>= 2 weeks must have elapsed since local palliative external radiation therapy (XRT) (small port)~>= 6 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if traumatic brain injury (TBI) was received~>= 4 weeks must have elapsed if other substantial bone marrow irradiation was given~Stem cell transplant or rescue without TBI: no evidence of active graft versus (vs.) host disease and >= 3 months must have elapsed since transplant; >= 4 weeks must have elapsed since any donor lymphocyte infusion~Patients must not be known to be refractory to red blood cell or platelet transfusions~Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):~Age: Maximum serum creatinine (mg/dL)~1 month to < 6 months: 0.4 (male) 0.4 (female)~6 months to < 1 year: 0.5 (male) 0.5 (female)~1 to < 2 years: 0.6 (male) 0.6 (female)~2 to < 6 years: 0.8 (male) 0.8 (female)~6 to < 10 years: 1 (male) 1 (female)~10 to < 13 years: 1.2 (male) 1.2 (female)~13 to < 16 years: 1.5 (male) 1.4 (female)~>= 16 years: 1.7 (male) 1.4 (female)~Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)~Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN (=< 135 U/L) (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L)~Serum albumin >= 2 g/dL (within 7 days prior to enrollment)~Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by multi-gated acquisition (MUGA)~Corrected QT (by Bazett's formula [QTcB]) interval < 450 msecs~Patients must be able to swallow tablets or liquid; use of a nasogastric or gastrostomy (G) tube is also allowed~Exclusion Criteria:~Patients who are pregnant or breast-feeding are not eligible for this study as there is yet no available information regarding human fetal or teratogenic toxicities; negative pregnancy tests must be obtained in girls who are post-menarchal; patients of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; women of childbearing potential should be advised to use effective contraception for 4 months after the last dose of trametinib; trametinib may also potentially be secreted in milk and therefore breastfeeding women are excluded; female patients should not breastfeed during treatment with trametinib, and for 4 months following the last dose; male patients must use a condom during intercourse and agree not to father a child during therapy and for 4 months following discontinuation of trametinib to avoid unnecessary exposure of trametinib to the fetus~Concomitant Medications~Corticosteroids: patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid~Note: hydrocortisone used as a pre-medication to prevent transfusion related reactions is not considered a concomitant corticosteroid~Investigational drugs: patients who are currently receiving another investigational drug are not eligible~Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible (except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)~Anti-graft versus host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial~Cardiac medications: any medications for treatment of left ventricular systolic dysfunction~Patients who have an uncontrolled infection are not eligible~Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible~Patients with a history of hepatic sinusoid obstructive syndrome (veno-occlusive disease) within the prior 3 months are not eligible~Patients with a history of or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible~Patients with a history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension~Patients with uncontrolled systemic disease(s) such as hypertension or diabetes mellitus are not eligible; blood pressure must be =< the 95th percentile for age, height, and gender~Patients with a history of allergic reaction attributed to compounds of similar chemical or biologic composition to the MEK inhibitor, trametinib are not eligible~Patients with a clinical diagnosis of Noonan syndrome are not eligible; Note: patients with Casitas B-lineage lymphoma (CBL) syndrome, also known as Noonan-like syndrome, are eligible to enroll
|
1 Month
|
21 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response | Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design. A responder is defined as a patient who achieves a best response of PR or CR on the study prior to having an overall response of PD; all others will be considered non-responders. | 12 cycles (1 cycle = 28 days) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will report the percentage of patients within each disease stratum who experienced a grade 3 or higher toxicity with attribution of possible, probable, or definite while on protocol therapy or within 30 days of the last dose of therapy. | Up to cycle 12 (1 cycle = 28 days) |
| Pharmacokinetic (PK) parameters of trametinib | A descriptive analysis of pharmacokinetic parameters of trametinib will be performed to define systemic exposure, drug clearance, Trametinib concentrations, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). | Up to cycle 12 (1 cycle = 28 days) |
| Trametinib concentrations | Will be measured by mass spectrometry. Will be analyzed descriptively. Values will be summarized with means and standard deviations. | Up to cycle 12 (1 cycle = 28 days) |
| Mutant allele burden | Will be measured by next-generation sequencing. Will be analyzed descriptively. Values will be summarized with means and standard deviations. | Up to cycle 12 (1 cycle = 28 days) |
| Complete Response | Complete Response rates will be calculated as the percent of evaluable patients who had an overall best response of Complete Response, and confidence intervals will be constructed accounting for the two-stage design. | 12 cycles (1 cycle = 28 days) |
| Duration of Response | The 2-year Event-Free Survival will be estimated using Kaplan-Meier methodology. | 2-year |
|
Trametinib, Antineoplastic Agents, Protein Kinase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (trametinib)<br>Patients receive trametinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a bone marrow aspiration or biopsy at baseline, on day 28 of cycles 1 and 2, at all subsequent odd numbered cycles, and at end of treatment. | Procedure: Bone Marrow Aspiration and Biopsy<br>* Undergo bone marrow aspiration or biopsy<br>Drug: Trametinib<br>* Given PO<br>* Other names: MEK Inhibitor GSK1120212;|
|
Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
Study Overview
=================
Brief Summary
-----------------
This phase II trial studies how well trametinib works in treating patients with juvenile myelomonocytic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
-----------------
PRIMARY OBJECTIVE: I. To determine the objective response rate to trametinib in children with recurrent or refractory juvenile myelomonocytic leukemia (JMML). SECONDARY OBJECTIVES: I. To further define and describe the toxicities of single agent trametinib in children with recurrent or refractory JMML. II. To further characterize the pharmacokinetics of trametinib in children with recurrent or refractory JMML. III. To prospectively evaluate mutant allele burden as a marker of disease activity in JMML. IV. To measure the rate of complete responses in children with recurrent or refractory JMML. V. To measure the duration of response among responders. EXPLORATORY OBJECTIVE: I. To describe the distribution of JMML diagnostic criteria in children with recurrent or refractory JMML. OUTLINE: Patients receive trametinib orally (PO) once daily (QD) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a bone marrow aspiration or biopsy at baseline, on day 28 of cycles 1 and 2, at all subsequent odd numbered cycles, and at end of treatment. After completion of study treatment, patients are followed up annually for up to 5 years.
Official Title
-----------------
A Phase 2 Study of the MEK Inhibitor Trametinib (NSC# 763093) in Children With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
Conditions
-----------------
Juvenile Myelomonocytic Leukemia, Neurofibromatosis Type 1
Intervention / Treatment
-----------------
* Procedure: Bone Marrow Aspiration and Biopsy
* Drug: Trametinib
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must be >= 1 month and < 22 years of age at the time of study entry Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease; the diagnosis is made based on the following criteria JMML category 1 (all of the following): the diagnostic criteria must include all features in category 1 and EITHER (i) one of the features in category 2 OR (ii) two features from category 3 to make the diagnosis Splenomegaly > 1000 (1 x 10^9/uL) circulating monocytes < 20% blasts in the bone marrow or peripheral blood Absence of the t(9;22) or BCR/ABL fusion gene JMML category 2 (at least one of the following if at least two category 3 criteria are not present): Somatic mutation in RAS or PTPN11 Clinical diagnosis of NF1 or NF1 gene mutation Homozygous mutation in CBL Monosomy 7 JMML category 3 (at least two of the following if no category 2 criteria are met): Circulating myeloid precursors White blood cell count, > 10 000 (10 x 10^9/ uL) Increased hemoglobin F for age Clonal cytogenetic abnormality GM-CSF hypersensitivity Patients with refractory or relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) demethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality; frontline therapy is defined as one cycle of intravenous chemotherapy that includes any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine; frontline therapy will also include any conditioning regimen as part of a stem cell transplant; patients who transform to AML at any point with more than 20% blasts are not eligible for this trial Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment Myelosuppressive chemotherapy: patients must have completely recovered from all acute toxic effects of chemotherapy, immunotherapy or radiotherapy prior to study enrollment; at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of protocol therapy Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur Monoclonal antibodies: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody Radiotherapy: >= 2 weeks must have elapsed since local palliative external radiation therapy (XRT) (small port) >= 6 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if traumatic brain injury (TBI) was received >= 4 weeks must have elapsed if other substantial bone marrow irradiation was given Stem cell transplant or rescue without TBI: no evidence of active graft versus (vs.) host disease and >= 3 months must have elapsed since transplant; >= 4 weeks must have elapsed since any donor lymphocyte infusion Patients must not be known to be refractory to red blood cell or platelet transfusions Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment): Age: Maximum serum creatinine (mg/dL) 1 month to < 6 months: 0.4 (male) 0.4 (female) 6 months to < 1 year: 0.5 (male) 0.5 (female) 1 to < 2 years: 0.6 (male) 0.6 (female) 2 to < 6 years: 0.8 (male) 0.8 (female) 6 to < 10 years: 1 (male) 1 (female) 10 to < 13 years: 1.2 (male) 1.2 (female) 13 to < 16 years: 1.5 (male) 1.4 (female) >= 16 years: 1.7 (male) 1.4 (female) Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN (=< 135 U/L) (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L) Serum albumin >= 2 g/dL (within 7 days prior to enrollment) Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by multi-gated acquisition (MUGA) Corrected QT (by Bazett's formula [QTcB]) interval < 450 msecs Patients must be able to swallow tablets or liquid; use of a nasogastric or gastrostomy (G) tube is also allowed Exclusion Criteria: Patients who are pregnant or breast-feeding are not eligible for this study as there is yet no available information regarding human fetal or teratogenic toxicities; negative pregnancy tests must be obtained in girls who are post-menarchal; patients of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; women of childbearing potential should be advised to use effective contraception for 4 months after the last dose of trametinib; trametinib may also potentially be secreted in milk and therefore breastfeeding women are excluded; female patients should not breastfeed during treatment with trametinib, and for 4 months following the last dose; male patients must use a condom during intercourse and agree not to father a child during therapy and for 4 months following discontinuation of trametinib to avoid unnecessary exposure of trametinib to the fetus Concomitant Medications Corticosteroids: patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid Note: hydrocortisone used as a pre-medication to prevent transfusion related reactions is not considered a concomitant corticosteroid Investigational drugs: patients who are currently receiving another investigational drug are not eligible Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible (except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy) Anti-graft versus host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial Cardiac medications: any medications for treatment of left ventricular systolic dysfunction Patients who have an uncontrolled infection are not eligible Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible Patients with a history of hepatic sinusoid obstructive syndrome (veno-occlusive disease) within the prior 3 months are not eligible Patients with a history of or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible Patients with a history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension Patients with uncontrolled systemic disease(s) such as hypertension or diabetes mellitus are not eligible; blood pressure must be =< the 95th percentile for age, height, and gender Patients with a history of allergic reaction attributed to compounds of similar chemical or biologic composition to the MEK inhibitor, trametinib are not eligible Patients with a clinical diagnosis of Noonan syndrome are not eligible; Note: patients with Casitas B-lineage lymphoma (CBL) syndrome, also known as Noonan-like syndrome, are eligible to enroll
Ages Eligible for Study
-----------------
Minimum Age: 1 Month
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
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (trametinib)<br>Patients receive trametinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a bone marrow aspiration or biopsy at baseline, on day 28 of cycles 1 and 2, at all subsequent odd numbered cycles, and at end of treatment. | Procedure: Bone Marrow Aspiration and Biopsy<br>* Undergo bone marrow aspiration or biopsy<br>Drug: Trametinib<br>* Given PO<br>* Other names: MEK Inhibitor GSK1120212;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response | Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design. A responder is defined as a patient who achieves a best response of PR or CR on the study prior to having an overall response of PD; all others will be considered non-responders. | 12 cycles (1 cycle = 28 days) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will report the percentage of patients within each disease stratum who experienced a grade 3 or higher toxicity with attribution of possible, probable, or definite while on protocol therapy or within 30 days of the last dose of therapy. | Up to cycle 12 (1 cycle = 28 days) |
| Pharmacokinetic (PK) parameters of trametinib | A descriptive analysis of pharmacokinetic parameters of trametinib will be performed to define systemic exposure, drug clearance, Trametinib concentrations, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). | Up to cycle 12 (1 cycle = 28 days) |
| Trametinib concentrations | Will be measured by mass spectrometry. Will be analyzed descriptively. Values will be summarized with means and standard deviations. | Up to cycle 12 (1 cycle = 28 days) |
| Mutant allele burden | Will be measured by next-generation sequencing. Will be analyzed descriptively. Values will be summarized with means and standard deviations. | Up to cycle 12 (1 cycle = 28 days) |
| Complete Response | Complete Response rates will be calculated as the percent of evaluable patients who had an overall best response of Complete Response, and confidence intervals will be constructed accounting for the two-stage design. | 12 cycles (1 cycle = 28 days) |
| Duration of Response | The 2-year Event-Free Survival will be estimated using Kaplan-Meier methodology. | 2-year |
|
|
NCT02050308
|
Web-based Smoking Cessation Program for Tribal College Students
|
The purpose of this study is to test the effectiveness of a culturally-tailored Internet-based program that helps American Indian (AI) tribal college students quit smoking.
|
Many of the approximately 25,000 American Indian (AI) students enrolled in tribal colleges/universities in the US arrive there as smokers. A 2011 study of high school seniors reported that the smoking prevalence among AI students is approximately 40%, the highest rate among all racial and ethnic groups studied. Although prevalence data on smoking among AI college students are limited, studies have shown that the majority of smokers in high school continue to smoke once they reach college. Prohibited from marketing to adolescents and children, the tobacco industry in recent years has shifted its most intense marketing to college students, resulting in increases in smoking rates among them. The transition to college provides amble opportunities for young adults to acquire new and harmful habits. Many of these habits do not seem so alien to young AIs: Cigarette smoking is the number one cause of preventable death among AIs. Cancer is the second leading cause of death among AIs, and lung cancer is the leading cause of cancer deaths for both AI men and women. Cultural factors, socioeconomic circumstances, and lack of culturally-tailored cessation programs for American Indian tribal college students have prevented access to effective interventions that promote smoking cessation. To date, few studies have focused on methods to encourage smoking cessation among tribal college students and no randomized clinical trials have yet been conducted. To address this public health deficit, we propose an innovative, effective, culturally and individually-tailored smoking cessation programs to promote cessation.~Primary aim is to: To test the effectiveness of a culturally-tailored internet-based smoking cessation intervention (I-ANBL) compared to an internet-based heart healthy diet (I-FV:fruit/vegetable) control condition in a randomized controlled trial with Tribal College students. Our hypothesis is that American Indian tribal college students randomized to the culturally-tailored smoking cessation arm will have significantly higher 7-day point prevalence abstinence (defined as no cigarettes in the past 7 days, biochemically verified) rates at 6 months than those receiving the heart healthy diet intervention.
|
Web-based Smoking Cessation Program for Tribal College Students
|
Smoking Cessation
|
* Other: Internet-All Nations Breath of Life (I-ANBL)
* Other: Honoring the Gift of Heart Health
* Drug: Nicotine gum, Patch, or Lozenge or Zyban® or Chantix®
|
Inclusion Criteria:~Currently enrolled at Salish Kootenai College~Have a valid telephone number and email address~Willing to participate in all study components~Willing to be followed-up for 6 months~Self identifies as American Indian or Alaska Native~Is a current smoker~Exclusion Criteria:~Planning to leave college within next 6 months~Medically ineligible as a result of screening questions
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 7-day Point Prevalence Abstinence | self-reported and biochemically (salivary cotinine) verified point prevalence abstinence, defined as no smoking for the previous 7 days, at the 6-month follow-up. | 6 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cigarettes Per Day | effect of intervention on the number of cigarettes smoked daily among those who continue to smoke at Month 6 | Change from Baseline in number of cigarettes smoked daily at 6 months |
| Number of Quit Attempts | comparison of the number of serious quit attempts between the two groups using Poisson regression | 6 months |
| Number of Participants Who Participated in All Sessions Over the Course of 6 Months. | Number of participants who participated in all online sessions and study protocol procedures over the course of 6 months | 6 months |
|
Molecular Mechanisms of Pharmacological Action, Nicotine, Varenicline, Ganglionic Stimulants, Autonomic Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Nicotinic Agonists, Cholinergic Agonists, Cholinergic Agents, Neurotransmitter Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Internet-All Nations Breath of Life (I-ANBL)<br>The culturally-tailored program includes 9 individual Internet-based sessions across a 12 week period and an additional individual Internet-based session at 6 months. Web sessions will last about half-an-hour (30 minutes) and will discuss topics that are important to quitting smoking (like: preparing to quit, dealing with cravings, and support systems, etc.) and topics relevant to American Indian culture (like traditional use of tobacco).~We plan to give participants in our cessation program a choice of varenicline, bupropion, nicotine replacement therapy or no pharmacotherapy. We choose to give our participants a choice because our experience shows that we would be unlikely to recruit AI participants into a trial that requires pharmacotherapy use. | Other: Internet-All Nations Breath of Life (I-ANBL)<br>* Participants will be asked to log into the website prior to the first session to allow for any problems with the site to be fixed prior to sessions starting. Topics we anticipate covering include, but are not limited to: preparing to quit, dealing with cravings, support systems, traditional tobacco, stress reduction, weight management, and staying quit, along with other topics determined during program development. For each session, the tribal college student will begin the session by answering a series of questions to produce an individually-tailored report that will be provided on the screen at the end of each week's session so that the smoker can work on strategies during the week before the next internet session~Weekly procedures will follow the same format as for the first session<br>Drug: Nicotine gum, Patch, or Lozenge or Zyban® or Chantix®<br>* Regardless of the intervention arm to which subjects are assigned, they will choose the option of nicotine replacement therapy they want, as long as they are eligible for it. All participants are offered the medications, but they do not have to take any medication to participate in the study.<br>* Other names: Nictotine Replacement Therapy (Nicotine gum, Patch, or Lozenge) or Pharmacotherapy (Zyban® or Chantix®);|
| Active Comparator: Honoring the Gift of Heart Health<br>The culturally-tailored program includes 9 individual Internet-based sessions across a 12 week period and an additional individual Internet-based session at 6 months. Web sessions will last about half-an-hour (30 minutes) and will discuss topics that are important to heart health (like: Assessing risk for heart disease, increasing fruit and vegetable consumption, physical activity, etc.).~We plan to give participants in our cessation program a choice of varenicline, bupropion, nicotine replacement therapy or no pharmacotherapy. We choose to give our participants a choice because our experience shows that we would be unlikely to recruit AI participants into a trial that requires pharmacotherapy use. | Other: Honoring the Gift of Heart Health<br>* These sessions help American Indians learn about what they can do to prevent heart disease. We will emphasize the increase consumption of fruits and vegetables as well as addressing other heart healthy activities. Honoring the Gift of Heart Health is a user-friendly program developed especially for American Indians. The manual provides the how-to for leading group education sessions. It offers hands-on activities that help people build the skills they need to make simple, practical, and lasting changes to help them fight heart disease. The protocol will follow procedures as the I-ANBL arm, however, this fruit and vegetable arm will not include individually tailored components, but just interactive web-based materials related to increasing heart health, including certain activities.<br>Drug: Nicotine gum, Patch, or Lozenge or Zyban® or Chantix®<br>* Regardless of the intervention arm to which subjects are assigned, they will choose the option of nicotine replacement therapy they want, as long as they are eligible for it. All participants are offered the medications, but they do not have to take any medication to participate in the study.<br>* Other names: Nictotine Replacement Therapy (Nicotine gum, Patch, or Lozenge) or Pharmacotherapy (Zyban® or Chantix®);|
|
Web-based Smoking Cessation Program for Tribal College Students
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test the effectiveness of a culturally-tailored Internet-based program that helps American Indian (AI) tribal college students quit smoking.
Detailed Description
-----------------
Many of the approximately 25,000 American Indian (AI) students enrolled in tribal colleges/universities in the US arrive there as smokers. A 2011 study of high school seniors reported that the smoking prevalence among AI students is approximately 40%, the highest rate among all racial and ethnic groups studied. Although prevalence data on smoking among AI college students are limited, studies have shown that the majority of smokers in high school continue to smoke once they reach college. Prohibited from marketing to adolescents and children, the tobacco industry in recent years has shifted its most intense marketing to college students, resulting in increases in smoking rates among them. The transition to college provides amble opportunities for young adults to acquire new and harmful habits. Many of these habits do not seem so alien to young AIs: Cigarette smoking is the number one cause of preventable death among AIs. Cancer is the second leading cause of death among AIs, and lung cancer is the leading cause of cancer deaths for both AI men and women. Cultural factors, socioeconomic circumstances, and lack of culturally-tailored cessation programs for American Indian tribal college students have prevented access to effective interventions that promote smoking cessation. To date, few studies have focused on methods to encourage smoking cessation among tribal college students and no randomized clinical trials have yet been conducted. To address this public health deficit, we propose an innovative, effective, culturally and individually-tailored smoking cessation programs to promote cessation. Primary aim is to: To test the effectiveness of a culturally-tailored internet-based smoking cessation intervention (I-ANBL) compared to an internet-based heart healthy diet (I-FV:fruit/vegetable) control condition in a randomized controlled trial with Tribal College students. Our hypothesis is that American Indian tribal college students randomized to the culturally-tailored smoking cessation arm will have significantly higher 7-day point prevalence abstinence (defined as no cigarettes in the past 7 days, biochemically verified) rates at 6 months than those receiving the heart healthy diet intervention.
Official Title
-----------------
Web-based Smoking Cessation Program for Tribal College Students
Conditions
-----------------
Smoking Cessation
Intervention / Treatment
-----------------
* Other: Internet-All Nations Breath of Life (I-ANBL)
* Other: Honoring the Gift of Heart Health
* Drug: Nicotine gum, Patch, or Lozenge or Zyban® or Chantix®
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Currently enrolled at Salish Kootenai College Have a valid telephone number and email address Willing to participate in all study components Willing to be followed-up for 6 months Self identifies as American Indian or Alaska Native Is a current smoker Exclusion Criteria: Planning to leave college within next 6 months Medically ineligible as a result of screening questions
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: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Internet-All Nations Breath of Life (I-ANBL)<br>The culturally-tailored program includes 9 individual Internet-based sessions across a 12 week period and an additional individual Internet-based session at 6 months. Web sessions will last about half-an-hour (30 minutes) and will discuss topics that are important to quitting smoking (like: preparing to quit, dealing with cravings, and support systems, etc.) and topics relevant to American Indian culture (like traditional use of tobacco). We plan to give participants in our cessation program a choice of varenicline, bupropion, nicotine replacement therapy or no pharmacotherapy. We choose to give our participants a choice because our experience shows that we would be unlikely to recruit AI participants into a trial that requires pharmacotherapy use. | Other: Internet-All Nations Breath of Life (I-ANBL)<br>* Participants will be asked to log into the website prior to the first session to allow for any problems with the site to be fixed prior to sessions starting. Topics we anticipate covering include, but are not limited to: preparing to quit, dealing with cravings, support systems, traditional tobacco, stress reduction, weight management, and staying quit, along with other topics determined during program development. For each session, the tribal college student will begin the session by answering a series of questions to produce an individually-tailored report that will be provided on the screen at the end of each week's session so that the smoker can work on strategies during the week before the next internet session Weekly procedures will follow the same format as for the first session<br>Drug: Nicotine gum, Patch, or Lozenge or Zyban® or Chantix®<br>* Regardless of the intervention arm to which subjects are assigned, they will choose the option of nicotine replacement therapy they want, as long as they are eligible for it. All participants are offered the medications, but they do not have to take any medication to participate in the study.<br>* Other names: Nictotine Replacement Therapy (Nicotine gum, Patch, or Lozenge) or Pharmacotherapy (Zyban® or Chantix®);|
| Active Comparator: Honoring the Gift of Heart Health<br>The culturally-tailored program includes 9 individual Internet-based sessions across a 12 week period and an additional individual Internet-based session at 6 months. Web sessions will last about half-an-hour (30 minutes) and will discuss topics that are important to heart health (like: Assessing risk for heart disease, increasing fruit and vegetable consumption, physical activity, etc.). We plan to give participants in our cessation program a choice of varenicline, bupropion, nicotine replacement therapy or no pharmacotherapy. We choose to give our participants a choice because our experience shows that we would be unlikely to recruit AI participants into a trial that requires pharmacotherapy use. | Other: Honoring the Gift of Heart Health<br>* These sessions help American Indians learn about what they can do to prevent heart disease. We will emphasize the increase consumption of fruits and vegetables as well as addressing other heart healthy activities. Honoring the Gift of Heart Health is a user-friendly program developed especially for American Indians. The manual provides the how-to for leading group education sessions. It offers hands-on activities that help people build the skills they need to make simple, practical, and lasting changes to help them fight heart disease. The protocol will follow procedures as the I-ANBL arm, however, this fruit and vegetable arm will not include individually tailored components, but just interactive web-based materials related to increasing heart health, including certain activities.<br>Drug: Nicotine gum, Patch, or Lozenge or Zyban® or Chantix®<br>* Regardless of the intervention arm to which subjects are assigned, they will choose the option of nicotine replacement therapy they want, as long as they are eligible for it. All participants are offered the medications, but they do not have to take any medication to participate in the study.<br>* Other names: Nictotine Replacement Therapy (Nicotine gum, Patch, or Lozenge) or Pharmacotherapy (Zyban® or Chantix®);|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With 7-day Point Prevalence Abstinence | self-reported and biochemically (salivary cotinine) verified point prevalence abstinence, defined as no smoking for the previous 7 days, at the 6-month follow-up. | 6 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cigarettes Per Day | effect of intervention on the number of cigarettes smoked daily among those who continue to smoke at Month 6 | Change from Baseline in number of cigarettes smoked daily at 6 months |
| Number of Quit Attempts | comparison of the number of serious quit attempts between the two groups using Poisson regression | 6 months |
| Number of Participants Who Participated in All Sessions Over the Course of 6 Months. | Number of participants who participated in all online sessions and study protocol procedures over the course of 6 months | 6 months |
|
|
NCT05272410
|
Cost-effectiveness of Controlling CPE
|
Spread of extensively drug-resistant bacteria (XDR) such as carbapenemase-producing Enterobacterales (CPE) is a major public health problem. Various prevention and control interventions are implemented to limit the transmission of XDR but they are expensive and often disrupt hospital organization. In this study, a mathematical model will be used to study the effectiveness and cost-effectiveness of control strategies to limit the spread of CPE in a general hospital ward. A case-control study will be conducted to estimate the excess length of stay and mortality attributable to CPE colonisation or infection.
|
Carbapenemase-producing Enterobacterales (CPE) are increasingly common in hospitals and represent a serious health problem. These multidrug-resistant organisms colonise the gastrointestinal tract after direct (person-to-person) or indirect (via contaminated surfaces) transmission and are a common cause of urinary tract infections, ventilator-associated pneumonia and bloodstream infections in healthcare settings. Treatment options for patients infected with CPE are limited leading to high mortality, increased length of hospital stay and hospital costs. The successful implementation of cost-effective infection control measures to prevent CPE spread and infections is key for infection control preventionists and hospital managers.~Recommendations to limit the transmission of CPE in healthcare facilities are based on the early detection of asymptomatic carriers, implementation of contact precautions and isolation in single room. In practice, strategies combining various interventions are employed according to the risk assessment and available resources: 1) universal or targeted rectal screening on admission, 2) standard precautions (SP), applied to all patients regardless of their infectious status, 3) contact precautions (CP) for identified carriers or infected patients, 4) isolation in a single room, 5) environmental cleaning, 6) rectal screening of contact patients, i.e. those whose care was provided by the same team as the CPE patient, and/or 7) isolation of carriers in a dedicated area with dedicated nursing staff (DNS), thereafter designated as cohorting.~However, these control measures pose challenges such as the high cost of patient's screening and cohorting, requirement for single room isolation or staff shortage for implementing precautions. Moreover, the effectiveness and cost-effectiveness of various CPE control strategies is under-documented.~OBJECTIVES:~Primary:~To evaluate the cost-effectiveness of different strategies combining screening and contact precaution measures to control the spread of CPE in a general medicine ward (GW) using a mathematical model.~Secondary:~To assess the impact of CPE colonisation/ infection on patient's outcome (mortality, length of stay)~To analyse the resources used to manage CPE cases~To analyse the care pathway of a CPE case and study whether carrying the CPE represents the opportunity loss for the patient,~METHODS AND TOOLS:~A dynamic, stochastic model simulates the transmission of CPE by the hands of healthcare workers (HCWs) and the environment in a hypothetical GW. Input parameters are based on data from APHP hospitals and from the literature.~12 strategies are compared to the baseline (no control) and combined different prevention and control interventions: targeted or universal screening at admission (TS or US), contact precautions (CP), isolation in a single room, dedicated nursing staff (DNS) for carriers and weekly screening of contact patients (WS). Time horizon is one year.~A hospital perspective is adopted to estimate costs, which included laboratory costs, single room, contact precautions, staff time, i.e. infection control nurse and/or nurses for cohorting, and lost bed-days due to prolonged hospital stay of identified carriers.~A case-control study will be conducted to assess the impact of CPE colonization / infection on patient's outcomes. Cases will be the patients newly identified as CPE colonized or infected during the first semester 2016 in the APHP hospital network, i.e. around 450 cases. In the case of hospital CPE outbreak, index and secondary cases will be included. Cases will be followed until discharge from the hospital setting, including rehabilitation or home care. Since all discharges in France, either from public or private HCFs, are registered in the single national hospital discharge database PMSI (HDD), it is possible to link all hospital stays and retrieve the entire hospital course.~Controls will be selected in the national HDD on a 1:1 ratio, based on the following matching criteria: absence of known colonization with CPE, age, gender, hospital stay in the same unit as the corresponding case during the 1st semester 2016, same DRG and duration of hospital stays at least as long at the time to colonization in the case.~The following information will be collected in cases and controls:~demographic data, country of born (and if so date of entry in France),~Charlson comorbidity score, McCabe score, activity of daily living (ADL) score at discharge from the index hospital stay,~main and secondary DRG in the HDD system,~socioeconomic status, estimated by the address of living (IRIS score), type of registration in the national insurance security,~origin at hospital admission, whether the case is an index or secondary CPE colonized/infected,~whether the case was only colonized or infected, type of Enterobacteriaceae carrying the resistance gene, and type of resistance gene~control measures implemented for controlling the episode: contact precautions, reinforced personnel, dedicated personnel, interruption of admission and transfers~activity of the unit of first admission: number of bed, yearly number of admissions and hospital days A cost-effectiveness analysis will be undertaken to find the most favourable control strategies from the model simulations. Sensitivity analysis will identify the factors that have the greatest impact on the results.
|
Cost-effectiveness of Strategies to Control the Spread of Carbapenemase-producing Enterobacteriaceae (CPE) in Hospitals
|
Carbapenemase-producing Enterobacteriaceae Infections
|
Inclusion Criteria:~patients infected with emerging highly resistant bacteria at acute care hospital.~Exclusion Criteria:~patients infected while hospitalized in intensive care unit.
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICER- the ratio of the difference in costs to difference in health benefits | The incremental cost-effectiveness ratios (ICER) calculated as the extra annual cost of one strategy relative to another divided by CPE cases avoided by that strategy relative to the other strategy | 12 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of CPE acquisitions | Number of CPE acquisitions observed for each strategy simulated in the model | 6 months after the end of the data collection |
| Costs of strategies | Description: costs associated with each strategy (e.g. laboratory costs, cost of single room, contact precautions, staff time) | 6 months after the end of the data collection |
| Number of days when hospital admissions interrupted | Number of days when the presence of EPC in a ward leads to the interruption of new admissions | 6 months after the end of the data collection |
| Number of days when hospital transfers interrupted | Description: Number of days when the presence of EPC in a ward leads to the interruption of transfers | 6 months after the end of the data collection |
| frequency of employment of dedicated staff | % of situations where dedicated staff were employed for the management of CPE cases | 6 months after the end of the data collection |
| length of hospital stay of patients | length of hospital stay for cases (CPE infected or colonised patients) and controls | 6 months after the end of the data collection |
| risk of death | risk of in-hospital death for cases (CPE infected or colonised patients) and controls | 6 months after the end of the data collection |
|
CPE spread, CPE infections, CPE deaths
|
Enterobacteriaceae Infections, Infections, Gram-Negative Bacterial Infections, Bacterial Infections, Bacterial Infections and Mycoses
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| cases<br>Patients colonized or infected with CPE | |
| controls<br>Patients not colonized or infected with CPE | |
|
Cost-effectiveness of Controlling CPE
Study Overview
=================
Brief Summary
-----------------
Spread of extensively drug-resistant bacteria (XDR) such as carbapenemase-producing Enterobacterales (CPE) is a major public health problem. Various prevention and control interventions are implemented to limit the transmission of XDR but they are expensive and often disrupt hospital organization. In this study, a mathematical model will be used to study the effectiveness and cost-effectiveness of control strategies to limit the spread of CPE in a general hospital ward. A case-control study will be conducted to estimate the excess length of stay and mortality attributable to CPE colonisation or infection.
Detailed Description
-----------------
Carbapenemase-producing Enterobacterales (CPE) are increasingly common in hospitals and represent a serious health problem. These multidrug-resistant organisms colonise the gastrointestinal tract after direct (person-to-person) or indirect (via contaminated surfaces) transmission and are a common cause of urinary tract infections, ventilator-associated pneumonia and bloodstream infections in healthcare settings. Treatment options for patients infected with CPE are limited leading to high mortality, increased length of hospital stay and hospital costs. The successful implementation of cost-effective infection control measures to prevent CPE spread and infections is key for infection control preventionists and hospital managers. Recommendations to limit the transmission of CPE in healthcare facilities are based on the early detection of asymptomatic carriers, implementation of contact precautions and isolation in single room. In practice, strategies combining various interventions are employed according to the risk assessment and available resources: 1) universal or targeted rectal screening on admission, 2) standard precautions (SP), applied to all patients regardless of their infectious status, 3) contact precautions (CP) for identified carriers or infected patients, 4) isolation in a single room, 5) environmental cleaning, 6) rectal screening of contact patients, i.e. those whose care was provided by the same team as the CPE patient, and/or 7) isolation of carriers in a dedicated area with dedicated nursing staff (DNS), thereafter designated as cohorting. However, these control measures pose challenges such as the high cost of patient's screening and cohorting, requirement for single room isolation or staff shortage for implementing precautions. Moreover, the effectiveness and cost-effectiveness of various CPE control strategies is under-documented. OBJECTIVES: Primary: To evaluate the cost-effectiveness of different strategies combining screening and contact precaution measures to control the spread of CPE in a general medicine ward (GW) using a mathematical model. Secondary: To assess the impact of CPE colonisation/ infection on patient's outcome (mortality, length of stay) To analyse the resources used to manage CPE cases To analyse the care pathway of a CPE case and study whether carrying the CPE represents the opportunity loss for the patient, METHODS AND TOOLS: A dynamic, stochastic model simulates the transmission of CPE by the hands of healthcare workers (HCWs) and the environment in a hypothetical GW. Input parameters are based on data from APHP hospitals and from the literature. 12 strategies are compared to the baseline (no control) and combined different prevention and control interventions: targeted or universal screening at admission (TS or US), contact precautions (CP), isolation in a single room, dedicated nursing staff (DNS) for carriers and weekly screening of contact patients (WS). Time horizon is one year. A hospital perspective is adopted to estimate costs, which included laboratory costs, single room, contact precautions, staff time, i.e. infection control nurse and/or nurses for cohorting, and lost bed-days due to prolonged hospital stay of identified carriers. A case-control study will be conducted to assess the impact of CPE colonization / infection on patient's outcomes. Cases will be the patients newly identified as CPE colonized or infected during the first semester 2016 in the APHP hospital network, i.e. around 450 cases. In the case of hospital CPE outbreak, index and secondary cases will be included. Cases will be followed until discharge from the hospital setting, including rehabilitation or home care. Since all discharges in France, either from public or private HCFs, are registered in the single national hospital discharge database PMSI (HDD), it is possible to link all hospital stays and retrieve the entire hospital course. Controls will be selected in the national HDD on a 1:1 ratio, based on the following matching criteria: absence of known colonization with CPE, age, gender, hospital stay in the same unit as the corresponding case during the 1st semester 2016, same DRG and duration of hospital stays at least as long at the time to colonization in the case. The following information will be collected in cases and controls: demographic data, country of born (and if so date of entry in France), Charlson comorbidity score, McCabe score, activity of daily living (ADL) score at discharge from the index hospital stay, main and secondary DRG in the HDD system, socioeconomic status, estimated by the address of living (IRIS score), type of registration in the national insurance security, origin at hospital admission, whether the case is an index or secondary CPE colonized/infected, whether the case was only colonized or infected, type of Enterobacteriaceae carrying the resistance gene, and type of resistance gene control measures implemented for controlling the episode: contact precautions, reinforced personnel, dedicated personnel, interruption of admission and transfers activity of the unit of first admission: number of bed, yearly number of admissions and hospital days A cost-effectiveness analysis will be undertaken to find the most favourable control strategies from the model simulations. Sensitivity analysis will identify the factors that have the greatest impact on the results.
Official Title
-----------------
Cost-effectiveness of Strategies to Control the Spread of Carbapenemase-producing Enterobacteriaceae (CPE) in Hospitals
Conditions
-----------------
Carbapenemase-producing Enterobacteriaceae Infections
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients infected with emerging highly resistant bacteria at acute care hospital. Exclusion Criteria: patients infected while hospitalized in intensive care unit.
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 |
| --- | --- |
| cases<br>Patients colonized or infected with CPE | |
| controls<br>Patients not colonized or infected with CPE | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICER- the ratio of the difference in costs to difference in health benefits | The incremental cost-effectiveness ratios (ICER) calculated as the extra annual cost of one strategy relative to another divided by CPE cases avoided by that strategy relative to the other strategy | 12 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of CPE acquisitions | Number of CPE acquisitions observed for each strategy simulated in the model | 6 months after the end of the data collection |
| Costs of strategies | Description: costs associated with each strategy (e.g. laboratory costs, cost of single room, contact precautions, staff time) | 6 months after the end of the data collection |
| Number of days when hospital admissions interrupted | Number of days when the presence of EPC in a ward leads to the interruption of new admissions | 6 months after the end of the data collection |
| Number of days when hospital transfers interrupted | Description: Number of days when the presence of EPC in a ward leads to the interruption of transfers | 6 months after the end of the data collection |
| frequency of employment of dedicated staff | % of situations where dedicated staff were employed for the management of CPE cases | 6 months after the end of the data collection |
| length of hospital stay of patients | length of hospital stay for cases (CPE infected or colonised patients) and controls | 6 months after the end of the data collection |
| risk of death | risk of in-hospital death for cases (CPE infected or colonised patients) and controls | 6 months after the end of the data collection |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CPE spread, CPE infections, CPE deaths
|
||
NCT05227521
|
Feasibility of the Adapted H-GRASP Feedback Program in the Chronic Phase Post Stroke.
|
In a recent cross-sectional study, it was shown that people with a good observed upper limb (UL) motor function but low perceived UL activity show a reduced daily-life UL activity. The investigators will now investigate the feasibility of a phone-monitored home exercise and feedback program for the UL following stroke and the preliminary effects on the perceived UL activity and actual daily-life UL activity for participants with good observed UL motor function but low perceived UL activity in the chronic phase post-stroke.
|
The Feasibility of the Adapted H-GRASP Feedback Program for Perceived and Daily Life UL Activity in Patients With Good Observed But Low Perceived Activity in the Chronic Phase Post Stroke: a Pilot Study.
|
Stroke
|
* Behavioral: Adapted H-GRASP feedback program
|
Inclusion Criteria:~Voluntary written informed consent of the participant has been obtained prior to any screening procedures~First-ever unilateral, supratentorial stroke, as defined by the American Heart Association/American Stroke Association~Minimum six months after stroke~Living in the community~≥18 years old~Good observed UL motor function but low perceived UL activity. Good observed UL motor function is defined as a score >50/66 on the Fugl-Meyer Assessment-Upper Extremity (FMA-UE). Low perceived UL activity is defined as a score ≤75/100 on the hand subscale of the Stroke Impact Scale version 3.0 (SIS-Hand).~Exclusion Criteria:~Other neurological condition than stroke~Musculoskeletal disorder that affects UL use~No informed consent~Participation in an interventional Study with an investigational medicinal product (IMP) or device
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate | % of individuals who were eligible and agreed to participate | 45 days (post-intervention) |
| Retention rate | % of participants who completed the intervention | 45 days (post-intervention) |
| Adherence to the intervention protocol | % of participants who achieved 12 hours of average weekly exercise | 45 days (post-intervention) |
| Safety | # of participants with increased pain while performing exercises as measured by visual analogue scale | 45 days (post-intervention) |
| Activity ratio | Contribution to the activity of one upper limb (UL) versus the other: hours of activity of the affected divided by the unaffected UL | Day 1 (enrolment) |
| Activity ratio | Contribution to the activity of one upper limb (UL) versus the other: hours of activity of the affected divided by the unaffected UL | Day 17 (baseline) |
| Activity ratio | Contribution to the activity of one upper limb (UL) versus the other: hours of activity of the affected divided by the unaffected UL | 45 days (post-intervention) |
| Hand subscale of the Stroke Impact Scale version 3.0 (SIS-Hand) | Perceived activity of the affected UL. Minimum 0 - maximum 100; higher scores mean better outcome. | Day 1 (enrolment) |
| Hand subscale of the Stroke Impact Scale version 3.0 (SIS-Hand) | Perceived activity of the affected UL. Minimum 0 - maximum 100; higher scores mean better outcome. | Day 17 (baseline) |
| Hand subscale of the Stroke Impact Scale version 3.0 (SIS-Hand) | Perceived activity of the affected UL. Minimum 0 - maximum 100; higher scores mean better outcome. | 45 days (post-intervention) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer motor assessment - upper extremity (FMA-UE) | Observed motor function of the affected UL (shoulder, arm, wrist, hand, and fingers) | Day 1 (enrolment), day 17 (baseline), 45 days (post-intervention) |
| Action Research Arm Test (ARAT) | Grasp, grip, pinch and gross movement of the affected UL | Day 17 (baseline), 45 days (post-intervention) |
| Motor Activity Log - 14 Item Version Amount Of Use (MAL-14 AOU) | Patient-reported amount of UL use in daily life | Day 17 (baseline), 45 days (post-intervention) |
| Motor Activity Log - 14 Item Version Quality Of Movement (MAL-14 QOM) | Patient-reported quality of UL use in daily life | Day 17 (baseline), 45 days (post-intervention) |
| Erasmus modified Nottingham Sensory Assessment (Em-NSA) | Sensory assessment of the UL | Day 17 (baseline), 45 days (post-intervention) |
| simplified modified Rankin Scale questionnaire (smRSq) | Global disability. Minimum 0 - maximum 5; higher scores mean worse outcome. | Day 17 (baseline), 45 days (post-intervention) |
| Hospital Anxiety and Depression Scale (HADS) | Symptoms of anxiety and depression. Minimum 0 - maximum 42; higher scores mean worse outcome. | Day 17 (baseline), 45 days (post-intervention) |
| Confidence in Arm and Hand Movement Scale (CAHM) | Perceived self-efficacy in performing tasks with the affected UL. Minimum 0 - maximum 100; higher scores mean better outcome. | Day 17 (baseline), 45 days (post-intervention) |
| Visual Analogue Scale (VAS) | Pain intensity in the affected UL from 0 (no pain) to 10 (extreme). Minimum 0, maximum 10, higher scores mean worse outcome. | Day 17 (baseline), 45 days (post-intervention) |
| EuroQol Five Dimensions Five Levels Questionnaire (EQ-5D-5L) | Health-related quality of life. Minimum 0, maximum 100, higher scores mean better outcome. | Day 17 (baseline), 45 days (post-intervention) |
| Hours of UL activity | Sum of all seconds recorded when the activity count was nonzero and converted to hours | Day 1 (enrolment), day 17 (baseline), 45 days (post-intervention) |
| Bilateral magnitude | Intensity of the movement: sum of the vector magnitude from the two ULs | Day 1 (enrolment), day 17 (baseline), 45 days (post-intervention) |
| Magnitude ratio | Contribution to the activity of one limb versus the other: natural log of the vector magnitude of the affected UL divided by the vector magnitude of the unaffected UL, whereby values greater than and less than -7 were replaced by 7 and -7, respectively, to categorize single limb movement. | Day 1 (enrolment), day 17 (baseline), 45 days (post-intervention) |
| Density plot | Graphical representation of accelerometry data from both ULs | Day 1 (enrolment), day 17 (baseline), 45 days (post-intervention) |
|
upper limb, daily life activity, home-based exercise program, feedback, perceived activity
|
Stroke, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AH-GRASP feedback intervention group<br>All study participants will receive the AH-GRASP feedback intervention. | Behavioral: Adapted H-GRASP feedback program<br>* Combination of the Home-Graded Repetitive Arm Supplementary Program with in home accelerometer-based feedback<br>|
|
Feasibility of the Adapted H-GRASP Feedback Program in the Chronic Phase Post Stroke.
Study Overview
=================
Brief Summary
-----------------
In a recent cross-sectional study, it was shown that people with a good observed upper limb (UL) motor function but low perceived UL activity show a reduced daily-life UL activity. The investigators will now investigate the feasibility of a phone-monitored home exercise and feedback program for the UL following stroke and the preliminary effects on the perceived UL activity and actual daily-life UL activity for participants with good observed UL motor function but low perceived UL activity in the chronic phase post-stroke.
Official Title
-----------------
The Feasibility of the Adapted H-GRASP Feedback Program for Perceived and Daily Life UL Activity in Patients With Good Observed But Low Perceived Activity in the Chronic Phase Post Stroke: a Pilot Study.
Conditions
-----------------
Stroke
Intervention / Treatment
-----------------
* Behavioral: Adapted H-GRASP feedback program
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Voluntary written informed consent of the participant has been obtained prior to any screening procedures First-ever unilateral, supratentorial stroke, as defined by the American Heart Association/American Stroke Association Minimum six months after stroke Living in the community ≥18 years old Good observed UL motor function but low perceived UL activity. Good observed UL motor function is defined as a score >50/66 on the Fugl-Meyer Assessment-Upper Extremity (FMA-UE). Low perceived UL activity is defined as a score ≤75/100 on the hand subscale of the Stroke Impact Scale version 3.0 (SIS-Hand). Exclusion Criteria: Other neurological condition than stroke Musculoskeletal disorder that affects UL use No informed consent Participation in an interventional Study with an investigational medicinal product (IMP) or device
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: AH-GRASP feedback intervention group<br>All study participants will receive the AH-GRASP feedback intervention. | Behavioral: Adapted H-GRASP feedback program<br>* Combination of the Home-Graded Repetitive Arm Supplementary Program with in home accelerometer-based feedback<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate | % of individuals who were eligible and agreed to participate | 45 days (post-intervention) |
| Retention rate | % of participants who completed the intervention | 45 days (post-intervention) |
| Adherence to the intervention protocol | % of participants who achieved 12 hours of average weekly exercise | 45 days (post-intervention) |
| Safety | # of participants with increased pain while performing exercises as measured by visual analogue scale | 45 days (post-intervention) |
| Activity ratio | Contribution to the activity of one upper limb (UL) versus the other: hours of activity of the affected divided by the unaffected UL | Day 1 (enrolment) |
| Activity ratio | Contribution to the activity of one upper limb (UL) versus the other: hours of activity of the affected divided by the unaffected UL | Day 17 (baseline) |
| Activity ratio | Contribution to the activity of one upper limb (UL) versus the other: hours of activity of the affected divided by the unaffected UL | 45 days (post-intervention) |
| Hand subscale of the Stroke Impact Scale version 3.0 (SIS-Hand) | Perceived activity of the affected UL. Minimum 0 - maximum 100; higher scores mean better outcome. | Day 1 (enrolment) |
| Hand subscale of the Stroke Impact Scale version 3.0 (SIS-Hand) | Perceived activity of the affected UL. Minimum 0 - maximum 100; higher scores mean better outcome. | Day 17 (baseline) |
| Hand subscale of the Stroke Impact Scale version 3.0 (SIS-Hand) | Perceived activity of the affected UL. Minimum 0 - maximum 100; higher scores mean better outcome. | 45 days (post-intervention) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer motor assessment - upper extremity (FMA-UE) | Observed motor function of the affected UL (shoulder, arm, wrist, hand, and fingers) | Day 1 (enrolment), day 17 (baseline), 45 days (post-intervention) |
| Action Research Arm Test (ARAT) | Grasp, grip, pinch and gross movement of the affected UL | Day 17 (baseline), 45 days (post-intervention) |
| Motor Activity Log - 14 Item Version Amount Of Use (MAL-14 AOU) | Patient-reported amount of UL use in daily life | Day 17 (baseline), 45 days (post-intervention) |
| Motor Activity Log - 14 Item Version Quality Of Movement (MAL-14 QOM) | Patient-reported quality of UL use in daily life | Day 17 (baseline), 45 days (post-intervention) |
| Erasmus modified Nottingham Sensory Assessment (Em-NSA) | Sensory assessment of the UL | Day 17 (baseline), 45 days (post-intervention) |
| simplified modified Rankin Scale questionnaire (smRSq) | Global disability. Minimum 0 - maximum 5; higher scores mean worse outcome. | Day 17 (baseline), 45 days (post-intervention) |
| Hospital Anxiety and Depression Scale (HADS) | Symptoms of anxiety and depression. Minimum 0 - maximum 42; higher scores mean worse outcome. | Day 17 (baseline), 45 days (post-intervention) |
| Confidence in Arm and Hand Movement Scale (CAHM) | Perceived self-efficacy in performing tasks with the affected UL. Minimum 0 - maximum 100; higher scores mean better outcome. | Day 17 (baseline), 45 days (post-intervention) |
| Visual Analogue Scale (VAS) | Pain intensity in the affected UL from 0 (no pain) to 10 (extreme). Minimum 0, maximum 10, higher scores mean worse outcome. | Day 17 (baseline), 45 days (post-intervention) |
| EuroQol Five Dimensions Five Levels Questionnaire (EQ-5D-5L) | Health-related quality of life. Minimum 0, maximum 100, higher scores mean better outcome. | Day 17 (baseline), 45 days (post-intervention) |
| Hours of UL activity | Sum of all seconds recorded when the activity count was nonzero and converted to hours | Day 1 (enrolment), day 17 (baseline), 45 days (post-intervention) |
| Bilateral magnitude | Intensity of the movement: sum of the vector magnitude from the two ULs | Day 1 (enrolment), day 17 (baseline), 45 days (post-intervention) |
| Magnitude ratio | Contribution to the activity of one limb versus the other: natural log of the vector magnitude of the affected UL divided by the vector magnitude of the unaffected UL, whereby values greater than and less than -7 were replaced by 7 and -7, respectively, to categorize single limb movement. | Day 1 (enrolment), day 17 (baseline), 45 days (post-intervention) |
| Density plot | Graphical representation of accelerometry data from both ULs | Day 1 (enrolment), day 17 (baseline), 45 days (post-intervention) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
upper limb, daily life activity, home-based exercise program, feedback, perceived activity
|
|
NCT03853798
|
Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007
|
This is a multicenter, open-label, extension study to evaluate the long-term safety, tolerability, and efficacy of treatment with AG-348 in participants who were previously enrolled in Study AG348-C-006 or Study AG348-C-007.
|
An Open-Label, Multicenter, Extension Study of AG-348 in Adult Subjects With Pyruvate Kinase Deficiency Previously Enrolled in AG-348 Studies
|
Pyruvate Kinase Deficiency
|
* Drug: AG-348
|
Inclusion Criteria:~Be willing and able to comply with study visits and procedures;~Have signed written informed consent prior to participating in this extension study;~Have completed either antecedent study AG348-C-006 or AG348-C-007 through the Part 2 Week 24 Visit;~Cohorts 2 and 3: Have demonstrated clinical benefit from AG-348 treatment in the antecedent study, in the opinion of the Investigator;~For women of reproductive potential, have a negative pregnancy test during screening;~For women of reproductive potential as well as men with partners who are women of reproductive potential, be abstinent as part of their usual lifestyle, or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of giving informed consent, during the study, and for 28 days following the last dose of study drug for women and 90 days following the last dose of study drug for men.~Exclusion Criteria:~Have a significant medical condition (including clinically significant laboratory abnormality) that developed during his/her antecedent AG- 348 study that confers an unacceptable risk to participating in this extension study, that could confound the interpretation of the study data, and/or that compromises the ability of the participant to complete study visits and procedures.~Are currently pregnant or breastfeeding.~Have a splenectomy scheduled during the study treatment period.~Meet the withdrawal criteria of his/her antecedent AG-348 study during screening of this extension study.~Are currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4 that have not been stopped for a duration of at least 5 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug; or strong inducers of CYP3A4 that have not been stopped for a duration of at least 28 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug on this extension study.~Have received anabolic steroids, including testosterone preparations, within 28 days prior to start of study drug on this extension study.~Have received hematopoietic stimulating agents (eg, erythropoietins, granulocyte colony stimulating factors, thrombopoietins) within 28 days prior to start of study drug on this extension study.~Have exposure to any investigational drug other than AG-348, device, or procedure within 3 months prior to start of study drug on this extension study.
|
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 |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | | From baseline to safety follow-up (up to 198 weeks) |
| Number of Participants with AEs Leading to Dose Reduction, Treatment Interruption and Treatment Discontinuation | | From baseline to safety follow-up (up to 198 weeks) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Hemoglobin (Hb) Response in Participants Who Previously Received Placebo in Study AG348-C-006 | | Weeks 16, 20, 24 |
| Area Under the Concentration-Time Curve (AUC) of AG-348 in Participants Who Previously Received Placebo in Study AG348-C-006 | | Week 12: pre-dose, post-dose at 30 minutes, 1 hour (h), 2 h, 4 h, 8 h |
| Maximum Observed Concentration of AG-348 in Participants Who Previously Received Placebo in Study AG348-C-006 | | Week 12: pre-dose, post-dose at 30 minutes, 1 h, 2 h, 4 h, 8 h |
| Change from Baseline in Hb Concentration | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Bilirubin | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Lactate Dehydrogenase (LDH) | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Haptoglobin Levels | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Reticulocyte Percentages | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Number of Transfusion Events | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Number of Red Blood Cell (RBC) Units Transfused | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Health-Related Quality of Life (HRQoL) Patient-Reported Outcome (PRO) Scores: Pyruvate Kinase Deficiency Diary (PKDD) | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in HRQoL PRO Scores: Pyruvate Kinase Deficiency Impact Assessment (PKDIA) | | From baseline up to Week 193 (Day 1) |
|
Mitapivat, Enzyme Activators, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participants who received placebo in Study AG348-C-006 will enroll in Cohort 1.~Part 1 (Dose Optimization Period, 12 weeks): Participants will begin by receiving 5 milligrams (mg) orally, twice a day. Each participant's dose of AG-348 may be increased to 20 mg twice a day and then to 50 mg twice a day depending on their response to AG-348 and tolerability.~Part 2 (Fixed Dose Period, 12 weeks): Last dose received in Part 1, twice a day.~After completion of Part 2, participants who, in the opinion of the Investigator, have demonstrated clinical benefit from AG-348 treatment will continue AG-348 treatment in the Continued Treatment Period. | Drug: AG-348<br>* Participants will receive 5, 20, or 50 mg twice a day for up to 192 weeks (not including dose taper) unless the dose is modified for reasons related to safety.<br>|
| Experimental: Cohort 2<br>Participants who received AG-348 in Study AG348-C-006 will enroll in Cohort 2.~Participants will continue the AG-348 dose regimen they were receiving at the last visit of Study AG348-C-006. | Drug: AG-348<br>* Participants will receive 5, 20, or 50 mg twice a day for up to 192 weeks (not including dose taper) unless the dose is modified for reasons related to safety.<br>|
| Experimental: Cohort 3<br>Participants who received AG-348 in Study AG348-C-007 will enroll in Cohort 3.~Participants will continue the AG-348 dose regimen they were receiving at the last visit of Study AG348-C-007. | Drug: AG-348<br>* Participants will receive 5, 20, or 50 mg twice a day for up to 192 weeks (not including dose taper) unless the dose is modified for reasons related to safety.<br>|
|
Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007
Study Overview
=================
Brief Summary
-----------------
This is a multicenter, open-label, extension study to evaluate the long-term safety, tolerability, and efficacy of treatment with AG-348 in participants who were previously enrolled in Study AG348-C-006 or Study AG348-C-007.
Official Title
-----------------
An Open-Label, Multicenter, Extension Study of AG-348 in Adult Subjects With Pyruvate Kinase Deficiency Previously Enrolled in AG-348 Studies
Conditions
-----------------
Pyruvate Kinase Deficiency
Intervention / Treatment
-----------------
* Drug: AG-348
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be willing and able to comply with study visits and procedures; Have signed written informed consent prior to participating in this extension study; Have completed either antecedent study AG348-C-006 or AG348-C-007 through the Part 2 Week 24 Visit; Cohorts 2 and 3: Have demonstrated clinical benefit from AG-348 treatment in the antecedent study, in the opinion of the Investigator; For women of reproductive potential, have a negative pregnancy test during screening; For women of reproductive potential as well as men with partners who are women of reproductive potential, be abstinent as part of their usual lifestyle, or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of giving informed consent, during the study, and for 28 days following the last dose of study drug for women and 90 days following the last dose of study drug for men. Exclusion Criteria: Have a significant medical condition (including clinically significant laboratory abnormality) that developed during his/her antecedent AG- 348 study that confers an unacceptable risk to participating in this extension study, that could confound the interpretation of the study data, and/or that compromises the ability of the participant to complete study visits and procedures. Are currently pregnant or breastfeeding. Have a splenectomy scheduled during the study treatment period. Meet the withdrawal criteria of his/her antecedent AG-348 study during screening of this extension study. Are currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4 that have not been stopped for a duration of at least 5 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug; or strong inducers of CYP3A4 that have not been stopped for a duration of at least 28 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug on this extension study. Have received anabolic steroids, including testosterone preparations, within 28 days prior to start of study drug on this extension study. Have received hematopoietic stimulating agents (eg, erythropoietins, granulocyte colony stimulating factors, thrombopoietins) within 28 days prior to start of study drug on this extension study. Have exposure to any investigational drug other than AG-348, device, or procedure within 3 months prior to start of study drug on this extension study.
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 1<br>Participants who received placebo in Study AG348-C-006 will enroll in Cohort 1. Part 1 (Dose Optimization Period, 12 weeks): Participants will begin by receiving 5 milligrams (mg) orally, twice a day. Each participant's dose of AG-348 may be increased to 20 mg twice a day and then to 50 mg twice a day depending on their response to AG-348 and tolerability. Part 2 (Fixed Dose Period, 12 weeks): Last dose received in Part 1, twice a day. After completion of Part 2, participants who, in the opinion of the Investigator, have demonstrated clinical benefit from AG-348 treatment will continue AG-348 treatment in the Continued Treatment Period. | Drug: AG-348<br>* Participants will receive 5, 20, or 50 mg twice a day for up to 192 weeks (not including dose taper) unless the dose is modified for reasons related to safety.<br>|
| Experimental: Cohort 2<br>Participants who received AG-348 in Study AG348-C-006 will enroll in Cohort 2. Participants will continue the AG-348 dose regimen they were receiving at the last visit of Study AG348-C-006. | Drug: AG-348<br>* Participants will receive 5, 20, or 50 mg twice a day for up to 192 weeks (not including dose taper) unless the dose is modified for reasons related to safety.<br>|
| Experimental: Cohort 3<br>Participants who received AG-348 in Study AG348-C-007 will enroll in Cohort 3. Participants will continue the AG-348 dose regimen they were receiving at the last visit of Study AG348-C-007. | Drug: AG-348<br>* Participants will receive 5, 20, or 50 mg twice a day for up to 192 weeks (not including dose taper) unless the dose is modified for reasons related to safety.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | | From baseline to safety follow-up (up to 198 weeks) |
| Number of Participants with AEs Leading to Dose Reduction, Treatment Interruption and Treatment Discontinuation | | From baseline to safety follow-up (up to 198 weeks) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Hemoglobin (Hb) Response in Participants Who Previously Received Placebo in Study AG348-C-006 | | Weeks 16, 20, 24 |
| Area Under the Concentration-Time Curve (AUC) of AG-348 in Participants Who Previously Received Placebo in Study AG348-C-006 | | Week 12: pre-dose, post-dose at 30 minutes, 1 hour (h), 2 h, 4 h, 8 h |
| Maximum Observed Concentration of AG-348 in Participants Who Previously Received Placebo in Study AG348-C-006 | | Week 12: pre-dose, post-dose at 30 minutes, 1 h, 2 h, 4 h, 8 h |
| Change from Baseline in Hb Concentration | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Bilirubin | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Lactate Dehydrogenase (LDH) | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Haptoglobin Levels | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Reticulocyte Percentages | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Number of Transfusion Events | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Number of Red Blood Cell (RBC) Units Transfused | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in Health-Related Quality of Life (HRQoL) Patient-Reported Outcome (PRO) Scores: Pyruvate Kinase Deficiency Diary (PKDD) | | From baseline up to Week 193 (Day 1) |
| Change from Baseline in HRQoL PRO Scores: Pyruvate Kinase Deficiency Impact Assessment (PKDIA) | | From baseline up to Week 193 (Day 1) |
|
||
NCT00024271
|
Surgery, Chemotherapy, and Radiation Therapy in Treating Patients With Peritoneal Cancer
|
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs directly into the tumor after surgery and combining them with radiation therapy may kill more tumor cells.~PURPOSE: Phase II trial to study the effectiveness of combining surgery, chemotherapy, and radiation therapy in treating patients who have peritoneal cancer.
|
OBJECTIVES:~Determine the response rate, duration of response, and duration of survival of patients with peritoneal mesothelioma treated with surgery, intraperitoneal chemotherapy, and whole abdominal radiotherapy.~Determine the toxicity of this regimen in these patients.~OUTLINE: Patients undergo initial surgery, including total omentectomy and excision of gross disease. Approximately 3-4 weeks after surgery, patients receive intraperitoneal (IP) chemotherapy consisting of doxorubicin IP over 2 hours once weekly on weeks 1, 4, 7, and 10 and cisplatin IP and gemcitabine IP once weekly on weeks 2, 5, 8, and 11. Patients also receive interferon gamma IP once weekly on weeks 13-16.~At approximately week 18-20, patients undergo second-look surgery. Patients with no gross disease receive hyperthermia mitomycin IP and cisplatin IP over 90 minutes.~Approximately 2-4 weeks after second-look surgery, patients undergo radiotherapy 5 days a week for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.~Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually for 5 years.~PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.
|
Phase II Trial Of Combined Resection, Intraperitoneal Chemotherapy, And Whole Abdominal Radiation For Treatment Of Peritoneal Mesothelioma
|
Malignant Mesothelioma
|
* Biological: recombinant interferon gamma
* Drug: cisplatin
* Drug: doxorubicin hydrochloride
* Drug: gemcitabine hydrochloride
* Drug: mitomycin C
* Procedure: conventional surgery
* Procedure: hyperthermia treatment
* Radiation: radiation therapy
|
DISEASE CHARACTERISTICS:~Histologically confirmed malignant mesothelioma~Measurable or evaluable disease~Ineligible for other high-priority study~No CNS metastases~PATIENT CHARACTERISTICS:~Age:~Over 18~Performance status:~SWOG 0-2~Karnofsky 60-100%~Life expectancy:~More than 2 months~Hematopoietic:~WBC greater than 3,000/mm3~Platelet count greater than 100,000/mm3~Hepatic:~Bilirubin less than 1.5 times normal~Renal:~Creatinine clearance at least 45 mL/min~BUN less than 1.5 times normal~No significant calcium abnormalities~Cardiovascular:~No symptomatic cardiovascular disease~No New York Heart Association class II, III, or IV heart disease~No congestive heart failure~No angina pectoris~No cardiac arrhythmia~No uncontrolled hypertension~Other:~No significant phosphate, electrolyte, or other metabolic abnormalities (e.g., metabolic acidosis)~No uncontrolled psychiatric disorder or neurologic disease~No seizure disorder~No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or skin cancer~No other serious medical or psychiatric illness~No uncontrolled serious infection~No senility or emotional instability~Not pregnant or nursing~Fertile patients must use effective contraception~PRIOR CONCURRENT THERAPY:~Biologic therapy:~Not specified~Chemotherapy:~No more than 2 prior chemotherapy regimens~No more than 1 prior intraperitoneal chemotherapy regimen~More than 6 weeks since prior chemotherapy~No other concurrent chemotherapy~Endocrine therapy:~No concurrent hormonal therapy except for nondisease-related conditions (e.g., insulin for diabetes)~Concurrent steroids for antiemesis, premedication, adrenal failure, or septic shock allowed~Radiotherapy:~No prior abdominal, pelvic, or lower chest radiotherapy~Surgery:~Prior surgical resection preceding disease recurrence allowed~More than 1 week since prior surgery
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
|
localized malignant mesothelioma, advanced malignant mesothelioma, recurrent malignant mesothelioma
|
Interferons, Interferon-gamma, Gemcitabine, Doxorubicin, Liposomal doxorubicin, Mitomycins, Mitomycin, Antineoplastic Agents, Antimetabolites, Antineoplastic, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Antibiotics, Antineoplastic, Topoisomerase II Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors, Antiviral Agents, Anti-Infective Agents, Alkylating Agents, Nucleic Acid Synthesis Inhibitors
|
| Intervention/Treatment |
| --- |
|Biological: recombinant interferon gamma|nan|
|Drug: cisplatin|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: gemcitabine hydrochloride|nan|
|Drug: mitomycin C|nan|
|Procedure: conventional surgery|nan|
|Procedure: hyperthermia treatment|nan|
|Radiation: radiation therapy|nan|
|
Surgery, Chemotherapy, and Radiation Therapy in Treating Patients With Peritoneal Cancer
Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs directly into the tumor after surgery and combining them with radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining surgery, chemotherapy, and radiation therapy in treating patients who have peritoneal cancer.
Detailed Description
-----------------
OBJECTIVES: Determine the response rate, duration of response, and duration of survival of patients with peritoneal mesothelioma treated with surgery, intraperitoneal chemotherapy, and whole abdominal radiotherapy. Determine the toxicity of this regimen in these patients. OUTLINE: Patients undergo initial surgery, including total omentectomy and excision of gross disease. Approximately 3-4 weeks after surgery, patients receive intraperitoneal (IP) chemotherapy consisting of doxorubicin IP over 2 hours once weekly on weeks 1, 4, 7, and 10 and cisplatin IP and gemcitabine IP once weekly on weeks 2, 5, 8, and 11. Patients also receive interferon gamma IP once weekly on weeks 13-16. At approximately week 18-20, patients undergo second-look surgery. Patients with no gross disease receive hyperthermia mitomycin IP and cisplatin IP over 90 minutes. Approximately 2-4 weeks after second-look surgery, patients undergo radiotherapy 5 days a week for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually for 5 years. PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.
Official Title
-----------------
Phase II Trial Of Combined Resection, Intraperitoneal Chemotherapy, And Whole Abdominal Radiation For Treatment Of Peritoneal Mesothelioma
Conditions
-----------------
Malignant Mesothelioma
Intervention / Treatment
-----------------
* Biological: recombinant interferon gamma
* Drug: cisplatin
* Drug: doxorubicin hydrochloride
* Drug: gemcitabine hydrochloride
* Drug: mitomycin C
* Procedure: conventional surgery
* Procedure: hyperthermia treatment
* Radiation: radiation therapy
Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed malignant mesothelioma Measurable or evaluable disease Ineligible for other high-priority study No CNS metastases PATIENT CHARACTERISTICS: Age: Over 18 Performance status: SWOG 0-2 Karnofsky 60-100% Life expectancy: More than 2 months Hematopoietic: WBC greater than 3,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 1.5 times normal Renal: Creatinine clearance at least 45 mL/min BUN less than 1.5 times normal No significant calcium abnormalities Cardiovascular: No symptomatic cardiovascular disease No New York Heart Association class II, III, or IV heart disease No congestive heart failure No angina pectoris No cardiac arrhythmia No uncontrolled hypertension Other: No significant phosphate, electrolyte, or other metabolic abnormalities (e.g., metabolic acidosis) No uncontrolled psychiatric disorder or neurologic disease No seizure disorder No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or skin cancer No other serious medical or psychiatric illness No uncontrolled serious infection No senility or emotional instability Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No more than 2 prior chemotherapy regimens No more than 1 prior intraperitoneal chemotherapy regimen More than 6 weeks since prior chemotherapy No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy except for nondisease-related conditions (e.g., insulin for diabetes) Concurrent steroids for antiemesis, premedication, adrenal failure, or septic shock allowed Radiotherapy: No prior abdominal, pelvic, or lower chest radiotherapy Surgery: Prior surgical resection preceding disease recurrence allowed More than 1 week since prior surgery
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
Arms and Interventions
| Intervention/Treatment |
| --- |
|Biological: recombinant interferon gamma|nan|
|Drug: cisplatin|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: gemcitabine hydrochloride|nan|
|Drug: mitomycin C|nan|
|Procedure: conventional surgery|nan|
|Procedure: hyperthermia treatment|nan|
|Radiation: radiation therapy|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
-----------------
localized malignant mesothelioma, advanced malignant mesothelioma, recurrent malignant mesothelioma
|
|
NCT00939276
|
Macular Edema Incidence/Severity Reduction With Nevanac
|
The purpose of this study is to evaluate NEVANAC in patients with diabetic retinopathy who developed macular edema (ME) within 90 days following cataract surgery.
| null |
Diabetic Retinopathy
|
* Drug: Nepafenac ophthalmic suspension, 0.1% (NEVANAC®)
* Drug: Nepafenac ophthalmic suspension vehicle
|
Inclusion Criteria:~Planned cataract extraction by phacoemulsification with the implantation of a posterior chamber intraocular lens (IOL) into the lens capsule.~History of Type 1 or Type 2 diabetes.~History of nonproliferative diabetic retinopathy (NPDR), mild, moderate, or severe, in the study eye as defined by the International Clinical Diabetic Retinopathy Disease Severity Scale.~Able to understand and sign an informed consent approved by an IRB/IEC.~Central subfield macular thickness less than or equal to 320 μm in the study eye prior to cataract surgery.~Absence of clinically significant macular edema in the study eye as detected by clinical exam.~Other protocol-defined inclusion criteria may apply.~Exclusion Criteria:~Signs of vitreomacular traction or epiretinal membrane in the study eye as detected by the reading center or Investigator.~Current or previous ocular disease other than diabetic retinopathy in the study eye that, in the opinion of the Investigator, would have confounded the assessments of the macula, the retina, or central vision.~Planned multiple procedures for the study eye during the cataract/IOL implantation surgery (eg, trabeculoplasty, corneal transplant).~Corneal transplant in study eye.~Baseline cumulative corneal fluorescein staining score (ie, sum of scores for all 5 corneal regions) for the study eye greater than or equal to 5, or baseline corneal fluorescein staining score in any single region for the study eye greater than or equal to 3.~Other protocol-defined exclusion criteria may apply.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who develop macular edema within 90 days following cataract surgery | | Time to event |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in best-corrected visual acuity (BCVA) from baseline to Day 90 | | Baseline, Day 90 |
|
cataract surgery, macular edema, prevention
|
Anti-Inflammatory Agents, Physiological Effects of Drugs, Nepafenac, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Antirheumatic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEVANAC<br>One drop instilled in the study eye 3 times daily (morning, midafternoon, and bedtime) beginning the day before surgery, continuing on the day of surgery and through the first 90 days following surgery | Drug: Nepafenac ophthalmic suspension, 0.1% (NEVANAC®)<br>* One drop instilled in the study eye 3 times daily (morning, midafternoon, and bedtime) beginning the day before surgery, continuing on the day of surgery and through the first 90 days following surgery<br>* Other names: NEVANAC®;|
| Placebo Comparator: Nepafenac Vehicle<br>One drop instilled in the study eye 3 times daily (morning, midafternoon, and bedtime) beginning the day before surgery, continuing on the day of surgery and through the first 90 days following surgery | Drug: Nepafenac ophthalmic suspension vehicle<br>* One drop instilled in the study eye 3 times daily (morning, midafternoon, and bedtime) beginning the day before surgery, continuing on the day of surgery and through the first 90 days following surgery<br>|
|
Macular Edema Incidence/Severity Reduction With Nevanac
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate NEVANAC in patients with diabetic retinopathy who developed macular edema (ME) within 90 days following cataract surgery.
Conditions
-----------------
Diabetic Retinopathy
Intervention / Treatment
-----------------
* Drug: Nepafenac ophthalmic suspension, 0.1% (NEVANAC®)
* Drug: Nepafenac ophthalmic suspension vehicle
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Planned cataract extraction by phacoemulsification with the implantation of a posterior chamber intraocular lens (IOL) into the lens capsule. History of Type 1 or Type 2 diabetes. History of nonproliferative diabetic retinopathy (NPDR), mild, moderate, or severe, in the study eye as defined by the International Clinical Diabetic Retinopathy Disease Severity Scale. Able to understand and sign an informed consent approved by an IRB/IEC. Central subfield macular thickness less than or equal to 320 μm in the study eye prior to cataract surgery. Absence of clinically significant macular edema in the study eye as detected by clinical exam. Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Signs of vitreomacular traction or epiretinal membrane in the study eye as detected by the reading center or Investigator. Current or previous ocular disease other than diabetic retinopathy in the study eye that, in the opinion of the Investigator, would have confounded the assessments of the macula, the retina, or central vision. Planned multiple procedures for the study eye during the cataract/IOL implantation surgery (eg, trabeculoplasty, corneal transplant). Corneal transplant in study eye. Baseline cumulative corneal fluorescein staining score (ie, sum of scores for all 5 corneal regions) for the study eye greater than or equal to 5, or baseline corneal fluorescein staining score in any single region for the study eye greater than or equal to 3. Other protocol-defined exclusion criteria may apply.
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: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEVANAC<br>One drop instilled in the study eye 3 times daily (morning, midafternoon, and bedtime) beginning the day before surgery, continuing on the day of surgery and through the first 90 days following surgery | Drug: Nepafenac ophthalmic suspension, 0.1% (NEVANAC®)<br>* One drop instilled in the study eye 3 times daily (morning, midafternoon, and bedtime) beginning the day before surgery, continuing on the day of surgery and through the first 90 days following surgery<br>* Other names: NEVANAC®;|
| Placebo Comparator: Nepafenac Vehicle<br>One drop instilled in the study eye 3 times daily (morning, midafternoon, and bedtime) beginning the day before surgery, continuing on the day of surgery and through the first 90 days following surgery | Drug: Nepafenac ophthalmic suspension vehicle<br>* One drop instilled in the study eye 3 times daily (morning, midafternoon, and bedtime) beginning the day before surgery, continuing on the day of surgery and through the first 90 days following surgery<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who develop macular edema within 90 days following cataract surgery | | Time to event |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in best-corrected visual acuity (BCVA) from baseline to Day 90 | | Baseline, Day 90 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cataract surgery, macular edema, prevention
|
|
NCT02704754
|
Suvorexant and Trauma Related Insomnia
|
Problems sleeping are common after exposure to highly threatening experiences and can occur with and without a diagnosis of posttraumatic stress disorder (PTSD). Established treatments for PTSD are limited for addressing insomnia and many insomnia treatments appear to be limited in the context of PTSD. Suvorexant is FDA approved for insomnia and among approved drugs has a unique mechanism of action that may be well suited for targetting arousal at night dysregulated by trauma. The investigators will evaluate the efficacy of suvorexant for insomnia that developed in relation to trauma exposure, utilizing a placebo control, and polysomnography to identify biomarkers of response, in a six week trial.
|
Disturbed sleep is one of the most common and distressing responses to exposure to severe trauma and can persist in many of those affected with and without accompanying posttraumatic stress disorder (PTSD). Insomnia is a risk factor for many of the conditions that are prevalent in trauma-exposed populations including PTSD, depression, and physical health conditions such as obesity, and cardiovascular disease. Trauma-related insomnia (TRI) is not typically differentiated in studies characterizing insomnia and its treatment, and insomnia accompanying PTSD has been shown to be relatively refractory to the treatments that are established for PTSD. Thus treatment of TRI presents an unmet need that has implications for the large and growing groups of people exposed to trauma in terms of relieving distress and preventing further psychiatric and medical morbidity.~Most of the data on TRI comes from research on populations with PTSD. Difficulty initiating and maintaining sleep is designated as one of the heightened arousal symptoms of PTSD in the DSM. Sleep studies have suggested increased wake after sleep onset (WASO), reduced slow wave sleep (SWS) in some PTSD populations and fragmented rapid eye movement (REM) sleep when PTSD is developing, and during its more acute stages. Suvorexant is a first in class orexin antagonist and is approved by the FDA for the indication of insomnia. Orexin antagonists dampen the activity of a specific arousal enhancing system in the brain during sleep. In rodent models suvorexant has been shown to enhance, and in healthy humans, to not affect slow wave and REM activity (in contrast with traditional hypnotics which can diminish both). Reducing arousal during sleep while reducing WASO and maintaining REM and slow wave sleep is a promising profile for the treatment of TRI. We are therefore proposing a placebo controlled evaluation to assess the efficacy of suvorexant for treating TRI with and without PTSD and its tolerability in these populations. We will include polysomnography (PSG) in order to have objective sleep outcomes and probe potential mechanisms and biomarkers predicting response. The proposed study will meet the objective below and test the following hypotheses:~Objective. To evaluate the efficacy of suvorexant for participants that meet criteria for insomnia and who identify a severely threatening event (DSM criterion A trauma) as a precipitant or a factor that significantly exacerbated their sleep disturbance.~The investigators hypothesize that suvorexant will improve subjective and objective indices of sleep disturbance; specifically, our primary outcome the polysomnographic (PSG) measure of sleep efficiency will be increased in the group receiving suvorexant compared with the group receiving placebo.~The effect of suvorexant versus placebo on the secondary outcome measures of the Insomnia Severity Index (ISI) scores and co-occurring symptoms of PTSD will also be evaluated.~Exploratory analyses will include comparison of response patterns among those with versus without significant symptoms of PTSD and relationships between increased in slow wave and rapid eye movement (REM) sleep and improvement in ISI scores and PTSD symptoms.~Adverse experiences and the tolerability of suvorexant in the recruited population with TRI will also be evaluated.
|
Suvorexant and Trauma Related Insomnia
|
Insomnia, Posttraumatic Stress Disorder
|
* Drug: suvorexant
* Other: placebo
|
Inclusion Criteria:~Physically healthy adults age 18-55 who meet DSM-5 criteria for insomnia and Criterion A (exposure to a traumatic event) for PTSD. The index trauma must have occurred within the past 5 years and at least 3 months before enrolling, and insomnia symptoms must have started or worsened after the exposure to the index trauma~Exclusion Criteria:~Psychiatric disorders other than insomnia, PTSD and specific phobias; including bipolar and psychotic disorders and meeting criteria for DSM-5 moderate alcohol or drug use disorders within the past year.~Diagnosis of a sleep disorder other than insomnia including PSG findings of apnea/hypopnea or periodic limb movement indices > 10/hour;~Medical conditions that require consistent use of medication or compromise sleep;~History of moderate to severe traumatic brain injury or mild traumatic brain injury with ongoing post-concussive symptoms;~Suicidal ideation with intent to act or with specific plan and intent in the past 6 months (Type 4 - 5 ideation on the Columbia Suicide Severity Rating Scale) or a concerning history of prior suicidal behavior.~Caffeine use exceeding 5 cups of coffee per day or its equivalent;~Habitual bedtimes after 3 AM, habitual rise times after 10 AM, or habitual napping > 1hour/day;~Pregnancy or breastfeeding, or expecting to conceive while in study;~Positive urine toxicology.
|
18 Years
|
55 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insomnia Severity Index Score From Baseline. | A seven-item measure used to evaluate insomnia severity for the preceding two weeks. Items are scored on a 5-point scale and a total score ranging between 0 and 28 is obtained by summing the seven items, with higher scores indicating greater insomnia severity. | Baseline score minus 6 weeks or last observation (measure was also obtained at 2 and 4 weeks, the mathematical mean for the last observation was 5 weeks). |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinician Administered PTSD Scale Score | Evaluates the frequency and intensity of each of the diagnostic symptoms of PTSD including nightmares and insomnia, total score was used which is a summation of all item scores, scores range between 0 to 80 with higher scores indicating more severe symptoms. | Baseline score minus 6 weeks or last observation (measure was also obtained at 2 and 4 weeks, the mathematical mean for the last observation was 5 weeks). |
| Polysomnographically Measured Wake After Sleep Onset | Polysomnography will provide objective measures of sleep, wake after sleep onset is the amount of wake time that occurs after initially falling asleep to the final awakening for the total sleep period measured in minutes. | Baseline values minus the values at 2 weeks. |
|
Suvorexant, Sleep Aids, Pharmaceutical, Hypnotics and Sedatives, Central Nervous System Depressants, Physiological Effects of Drugs, Orexin Receptor Antagonists, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: suvorexant<br>10mg administered before bedtime, during the first week; if well tolerated then the dose is increased to 20 mg before bedtime. | Drug: suvorexant<br>* First in class orexin antagonist recently approved by the FDA for the treatment of insomnia<br>* Other names: Belsomra;|
| Placebo Comparator: Placebo pill<br>A pill without active ingredients~Randomization occurs 1:1 with stratification for gender and PTSD status. | Other: placebo<br>* Pill with inactive ingredients<br>|
|
Suvorexant and Trauma Related Insomnia
Study Overview
=================
Brief Summary
-----------------
Problems sleeping are common after exposure to highly threatening experiences and can occur with and without a diagnosis of posttraumatic stress disorder (PTSD). Established treatments for PTSD are limited for addressing insomnia and many insomnia treatments appear to be limited in the context of PTSD. Suvorexant is FDA approved for insomnia and among approved drugs has a unique mechanism of action that may be well suited for targetting arousal at night dysregulated by trauma. The investigators will evaluate the efficacy of suvorexant for insomnia that developed in relation to trauma exposure, utilizing a placebo control, and polysomnography to identify biomarkers of response, in a six week trial.
Detailed Description
-----------------
Disturbed sleep is one of the most common and distressing responses to exposure to severe trauma and can persist in many of those affected with and without accompanying posttraumatic stress disorder (PTSD). Insomnia is a risk factor for many of the conditions that are prevalent in trauma-exposed populations including PTSD, depression, and physical health conditions such as obesity, and cardiovascular disease. Trauma-related insomnia (TRI) is not typically differentiated in studies characterizing insomnia and its treatment, and insomnia accompanying PTSD has been shown to be relatively refractory to the treatments that are established for PTSD. Thus treatment of TRI presents an unmet need that has implications for the large and growing groups of people exposed to trauma in terms of relieving distress and preventing further psychiatric and medical morbidity. Most of the data on TRI comes from research on populations with PTSD. Difficulty initiating and maintaining sleep is designated as one of the heightened arousal symptoms of PTSD in the DSM. Sleep studies have suggested increased wake after sleep onset (WASO), reduced slow wave sleep (SWS) in some PTSD populations and fragmented rapid eye movement (REM) sleep when PTSD is developing, and during its more acute stages. Suvorexant is a first in class orexin antagonist and is approved by the FDA for the indication of insomnia. Orexin antagonists dampen the activity of a specific arousal enhancing system in the brain during sleep. In rodent models suvorexant has been shown to enhance, and in healthy humans, to not affect slow wave and REM activity (in contrast with traditional hypnotics which can diminish both). Reducing arousal during sleep while reducing WASO and maintaining REM and slow wave sleep is a promising profile for the treatment of TRI. We are therefore proposing a placebo controlled evaluation to assess the efficacy of suvorexant for treating TRI with and without PTSD and its tolerability in these populations. We will include polysomnography (PSG) in order to have objective sleep outcomes and probe potential mechanisms and biomarkers predicting response. The proposed study will meet the objective below and test the following hypotheses: Objective. To evaluate the efficacy of suvorexant for participants that meet criteria for insomnia and who identify a severely threatening event (DSM criterion A trauma) as a precipitant or a factor that significantly exacerbated their sleep disturbance. The investigators hypothesize that suvorexant will improve subjective and objective indices of sleep disturbance; specifically, our primary outcome the polysomnographic (PSG) measure of sleep efficiency will be increased in the group receiving suvorexant compared with the group receiving placebo. The effect of suvorexant versus placebo on the secondary outcome measures of the Insomnia Severity Index (ISI) scores and co-occurring symptoms of PTSD will also be evaluated. Exploratory analyses will include comparison of response patterns among those with versus without significant symptoms of PTSD and relationships between increased in slow wave and rapid eye movement (REM) sleep and improvement in ISI scores and PTSD symptoms. Adverse experiences and the tolerability of suvorexant in the recruited population with TRI will also be evaluated.
Official Title
-----------------
Suvorexant and Trauma Related Insomnia
Conditions
-----------------
Insomnia, Posttraumatic Stress Disorder
Intervention / Treatment
-----------------
* Drug: suvorexant
* Other: placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Physically healthy adults age 18-55 who meet DSM-5 criteria for insomnia and Criterion A (exposure to a traumatic event) for PTSD. The index trauma must have occurred within the past 5 years and at least 3 months before enrolling, and insomnia symptoms must have started or worsened after the exposure to the index trauma Exclusion Criteria: Psychiatric disorders other than insomnia, PTSD and specific phobias; including bipolar and psychotic disorders and meeting criteria for DSM-5 moderate alcohol or drug use disorders within the past year. Diagnosis of a sleep disorder other than insomnia including PSG findings of apnea/hypopnea or periodic limb movement indices > 10/hour; Medical conditions that require consistent use of medication or compromise sleep; History of moderate to severe traumatic brain injury or mild traumatic brain injury with ongoing post-concussive symptoms; Suicidal ideation with intent to act or with specific plan and intent in the past 6 months (Type 4 - 5 ideation on the Columbia Suicide Severity Rating Scale) or a concerning history of prior suicidal behavior. Caffeine use exceeding 5 cups of coffee per day or its equivalent; Habitual bedtimes after 3 AM, habitual rise times after 10 AM, or habitual napping > 1hour/day; Pregnancy or breastfeeding, or expecting to conceive while in study; Positive urine toxicology.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 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: suvorexant<br>10mg administered before bedtime, during the first week; if well tolerated then the dose is increased to 20 mg before bedtime. | Drug: suvorexant<br>* First in class orexin antagonist recently approved by the FDA for the treatment of insomnia<br>* Other names: Belsomra;|
| Placebo Comparator: Placebo pill<br>A pill without active ingredients Randomization occurs 1:1 with stratification for gender and PTSD status. | Other: placebo<br>* Pill with inactive ingredients<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insomnia Severity Index Score From Baseline. | A seven-item measure used to evaluate insomnia severity for the preceding two weeks. Items are scored on a 5-point scale and a total score ranging between 0 and 28 is obtained by summing the seven items, with higher scores indicating greater insomnia severity. | Baseline score minus 6 weeks or last observation (measure was also obtained at 2 and 4 weeks, the mathematical mean for the last observation was 5 weeks). |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinician Administered PTSD Scale Score | Evaluates the frequency and intensity of each of the diagnostic symptoms of PTSD including nightmares and insomnia, total score was used which is a summation of all item scores, scores range between 0 to 80 with higher scores indicating more severe symptoms. | Baseline score minus 6 weeks or last observation (measure was also obtained at 2 and 4 weeks, the mathematical mean for the last observation was 5 weeks). |
| Polysomnographically Measured Wake After Sleep Onset | Polysomnography will provide objective measures of sleep, wake after sleep onset is the amount of wake time that occurs after initially falling asleep to the final awakening for the total sleep period measured in minutes. | Baseline values minus the values at 2 weeks. |
|
|
NCT01923818
|
Treatment of Rivaroxaban Versus Aspirin for Non-disabling Cerebrovascular Events
|
Transient ischemic attack (TIA) or minor ischemic stroke has a high risk of early recurrent stroke. As the golden standard, aspirin effect modestly on acute ischemic stroke, and slightly increase the risk of intracerebral hemorrhage. Recently, rivaroxaban, a new oral anticoagulant, is proved to be as effective as traditional anticoagulants, while carrying significantly less risk of intracranial hemorrhage.~The TRACE trial is a randomized, double-blind, multicenter, controlled clinical trial in China. The investigators will assess the hypothesis that a 30-days rivaroxaban regimen is superior to aspirin alone for the treatment of high-risk patients with acute nondisabling cerebrovascular event.
|
The TRACE study is a randomized, double-blind clinical trial with a target enrollment of 3,700 Chinese patients. Two subtypes of patients will be enrolled: I, acute disabling ischemic stroke (<24 hours of symptoms onset); II, acute TIA (<24 hours of symptoms onset).~Patients will be randomized into 3 groups:~Receiving a 100-mg dose of aspirin and placebo rivaroxaban from day 1 to day 30~Receiving a 5-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30~Receiving a 10-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30~The primary efficacy end point is percentage of patients with new stroke (ischemic or hemorrhage) at 90 days.
|
Randomized,Double-blind Trial Comparing the Effects of a Rivaroxaban Regimen During the First 30 Days,Versus Aspirin for the Acute Treatment of TIA or Minor Stroke
|
Ischemic Stroke, TIA
|
* Drug: rivaroxaban
* Drug: Aspirin
* Drug: placebo
|
Inclusion Criteria:~Adult subjects (male or female ≥18 years old)~Acute nondisabling ischemic stroke (NIHSS ≤3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset. Symptom onset is defined by the last see normal principle~TIA (neurologic deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with investigational medication within 24 hours of symptoms onset. Symptom onset is defined by the last see normal principle~Informed consent signed~Exclusion Criteria:~Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major nonischemic brain disease, on baseline head CT or MRI scan~mRS score >2 at randomization (premorbid historical assessment)~NIHSS ≥4 at randomization~Clear indication for anticoagulation (atrial fibrillation, mechanical cardiac valves, deep venous thrombosis, pulmonary embolism or known hypercoagulable state)~Contraindication to investigational medications~Thrombolysis for ischemic stroke within preceding 7 days~History of intracranial hemorrhage~Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anticoagulation~Gastrointestinal bleed or major surgery within 3 months~Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months~TIA or minor stroke induced by angiography or surgery~Severe noncardiovascular comorbidity with life expectancy <3 months~Women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test result~Severe renal failure, defined as Glomerular Filtration Rate (GFR) <30 ml/min Severe hepatic insufficiency (Child-Pugh score B to C)
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of patients with new stroke (ischemic or hemorrhage) | | 90 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death) | | 30 days |
| mRS score changes (continuous) and dichotomized at percentage with score 0 to 2 versus 3 to 6 | | 30 days and 90 days |
| Changes in NIHSS scores | | 90 days |
| moderate to severe bleeding events | | 90 days |
| Total mortality | | 90 days |
| Adverse events/severe adverse events reported by the investigators | | 90 days |
|
rivaroxaban, aspirin, new oral anticoagulant, TIA, acute minor ischemic stroke
|
Aspirin, Rivaroxaban, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Inflammatory Agents, Antirheumatic Agents, Fibrinolytic Agents, Fibrin Modulating Agents, Molecular Mechanisms of Pharmacological Action, Platelet Aggregation Inhibitors, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Antipyretics, Factor Xa Inhibitors, Antithrombins, Serine Proteinase Inhibitors, Protease Inhibitors, Anticoagulants
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: aspirin<br>Receiving a 100-mg dose of aspirin and placebo rivaroxaban from day 1 to day 30 | Drug: Aspirin<br>* non-steroidal anti-inflammatory drugs<br>* Other names: Acetylsalicylic acid;Drug: placebo<br> <br> |
| Experimental: Rivaroxaban 5mg<br>Receiving a 5-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30 | Drug: rivaroxaban<br>* orally active direct factor Xa inhibitor<br>* Other names: Xarelto;Drug: placebo<br> <br> |
| Experimental: rivaroxaban 10mg<br>Receiving a 10-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30 | Drug: rivaroxaban<br>* orally active direct factor Xa inhibitor<br>* Other names: Xarelto;Drug: placebo<br> <br> |
|
Treatment of Rivaroxaban Versus Aspirin for Non-disabling Cerebrovascular Events
Study Overview
=================
Brief Summary
-----------------
Transient ischemic attack (TIA) or minor ischemic stroke has a high risk of early recurrent stroke. As the golden standard, aspirin effect modestly on acute ischemic stroke, and slightly increase the risk of intracerebral hemorrhage. Recently, rivaroxaban, a new oral anticoagulant, is proved to be as effective as traditional anticoagulants, while carrying significantly less risk of intracranial hemorrhage. The TRACE trial is a randomized, double-blind, multicenter, controlled clinical trial in China. The investigators will assess the hypothesis that a 30-days rivaroxaban regimen is superior to aspirin alone for the treatment of high-risk patients with acute nondisabling cerebrovascular event.
Detailed Description
-----------------
The TRACE study is a randomized, double-blind clinical trial with a target enrollment of 3,700 Chinese patients. Two subtypes of patients will be enrolled: I, acute disabling ischemic stroke (<24 hours of symptoms onset); II, acute TIA (<24 hours of symptoms onset). Patients will be randomized into 3 groups: Receiving a 100-mg dose of aspirin and placebo rivaroxaban from day 1 to day 30 Receiving a 5-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30 Receiving a 10-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30 The primary efficacy end point is percentage of patients with new stroke (ischemic or hemorrhage) at 90 days.
Official Title
-----------------
Randomized,Double-blind Trial Comparing the Effects of a Rivaroxaban Regimen During the First 30 Days,Versus Aspirin for the Acute Treatment of TIA or Minor Stroke
Conditions
-----------------
Ischemic Stroke, TIA
Intervention / Treatment
-----------------
* Drug: rivaroxaban
* Drug: Aspirin
* Drug: placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult subjects (male or female ≥18 years old) Acute nondisabling ischemic stroke (NIHSS ≤3 at the time of randomization) that can be treated with study drug within 24 hours of symptoms onset. Symptom onset is defined by the last see normal principle TIA (neurologic deficit attributed to focal brain ischemia, with resolution of the deficit within 24 hours of symptom onset), that can be treated with investigational medication within 24 hours of symptoms onset. Symptom onset is defined by the last see normal principle Informed consent signed Exclusion Criteria: Diagnosis of hemorrhage or other pathology, such as vascular malformation, tumor, abscess or other major nonischemic brain disease, on baseline head CT or MRI scan mRS score >2 at randomization (premorbid historical assessment) NIHSS ≥4 at randomization Clear indication for anticoagulation (atrial fibrillation, mechanical cardiac valves, deep venous thrombosis, pulmonary embolism or known hypercoagulable state) Contraindication to investigational medications Thrombolysis for ischemic stroke within preceding 7 days History of intracranial hemorrhage Current treatment (last dose given within 10 days before randomization) with heparin therapy or oral anticoagulation Gastrointestinal bleed or major surgery within 3 months Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months TIA or minor stroke induced by angiography or surgery Severe noncardiovascular comorbidity with life expectancy <3 months Women of childbearing age not practicing reliable contraception who do not have a documented negative pregnancy test result Severe renal failure, defined as Glomerular Filtration Rate (GFR) <30 ml/min Severe hepatic insufficiency (Child-Pugh score B to C)
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: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: aspirin<br>Receiving a 100-mg dose of aspirin and placebo rivaroxaban from day 1 to day 30 | Drug: Aspirin<br>* non-steroidal anti-inflammatory drugs<br>* Other names: Acetylsalicylic acid;Drug: placebo<br> <br> |
| Experimental: Rivaroxaban 5mg<br>Receiving a 5-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30 | Drug: rivaroxaban<br>* orally active direct factor Xa inhibitor<br>* Other names: Xarelto;Drug: placebo<br> <br> |
| Experimental: rivaroxaban 10mg<br>Receiving a 10-mg dose of rivaroxaban and placebo aspirin from day 1 to day 30 | Drug: rivaroxaban<br>* orally active direct factor Xa inhibitor<br>* Other names: Xarelto;Drug: placebo<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of patients with new stroke (ischemic or hemorrhage) | | 90 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death) | | 30 days |
| mRS score changes (continuous) and dichotomized at percentage with score 0 to 2 versus 3 to 6 | | 30 days and 90 days |
| Changes in NIHSS scores | | 90 days |
| moderate to severe bleeding events | | 90 days |
| Total mortality | | 90 days |
| Adverse events/severe adverse events reported by the investigators | | 90 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
rivaroxaban, aspirin, new oral anticoagulant, TIA, acute minor ischemic stroke
|
NCT04258592
|
18F-MFBG PET Imaging of the Norepinephrine Transporter in Neural Crest and Neuroendocrine Tumors
|
The aim of this study is to evaluate the potential and feasibility of 18F-metafluorobenzylguanidine (18F-MFBG) positron emission tomography (PET) in patients with neural crest and neuroendocrine tumors.
|
Ten neural crest tumor or neuroendocrine tumor (NET) patients, with a routine clinical 123I-metaiodobenzylguanidine (123I-MIBG imaging) (planar + single photon emission tomography (SPECT)) performed in the previous six months or scheduled within three months, will undergo a dynamic PET scan for the first 30 minutes, followed by 3 static whole-body PET/CTs up to three hours post injection for a pharmacokinetics study and efficacy assessment of 18F-MFBG in humans. Furthermore, a comparison with 123I-MIBG imaging will be performed.
|
18F-MFBG PET Imaging of the Norepinephrine Transporter in Neural Crest and Neuroendocrine Tumors: a Phase I PET/CT Study
|
Neural Crest Tumor, Neuroendocrine Tumors
|
* Drug: (18F)MFBG
* Device: PET/CT
* Other: Venous blood samples
|
Inclusion Criteria:~Subject is aged 1 year or older~Signed Informed Consent by the participant (adult) or his/her parents or legal guardian (minors)~Subject is diagnosed with a neural crest tumor or neuroendocrine tumor~Subject is judged to be in good general condition by the investigator on the basis of medical history, physical examination including vital signs and clinical laboratory tests, besides the diagnosis of a neural crest tumor~Subject should have a routine clinical 123I-MIBG scintigraphy (planar + SPECT/CT) performed within 6 months prior to the inclusion visit or scheduled within 3 months after the inclusion visit~Adult female subjects should be post-menopausal or surgically sterile or using effective contraceptive with negative pregnancy test. Minor female participants of childbearing potential that are sexually active should be using effective contraceptive with negative pregnancy test~Exclusion Criteria:~Subject has a previous or ongoing recurrent or chronic disease, other than a neural crest tumor, at high risk to interfere with the evaluation of the trial according to the judgement of the investigator, e.g. known gastro-intestinal, hepatic, renal, cardiovascular, metabolic or hormonal disease, cancer, major neurological or convulsive disorder or any psychiatric disease~Subject is currently, or within two weeks prior to the inclusion visit, a user (including ''recreational use'') of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse~Subject is unable to refrain from smoking more than 10 cigarettes per day during the study~Subject has had exposure to ionizing radiation (> 1 mSv) in other research studies within the last 12 months~Subject suffers from claustrophobia or cannot tolerate confinement during PET/CT scanning procedures~Adult subject cannot lie still for 45 minutes inside the scanner. Minor participant cannot lie still for the duration of at least one whole-body PET/CT, varying from 15 to 30 minutes depending on the length of the child, except for children who will be sedated for one scan~Subject is unwilling to avoid unusual, unaccustomed, or strenuous physical activity (i.e. weight lifting, running, bicycling) from the time of the selection visit until the final safety telephone follow-up interview~Subject or his/her parents or legal guardian in case of minors, does not understand the study procedure~Subject is unwilling or unable to perform all of the study procedures, or is considered unsuitable in any way by the principal investigator.~Subject is potentially pregnant (serum and urinary hCG test will be performed in women where pregnancy is not excluded) or is breast-feeding~Subject has recently (< 30 days or 5 times the plasma half-life of the investigated drug, whichever is longest) participated or is simultaneously participating in another prospective interventional clinical trial~Subject has a history of multiple and/or severe allergies to drugs or food~Subject underwent surgery between the selection and inclusion visit~Adult subject is mentally or legally incapacitated
|
1 Year
| null |
All
|
No
|
Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmation of 18F-MFBG as a hNET imaging agent in patients with neural crest and neuroendocrine tumors. | The primary endpoint will be met if in 8 out of 10 patients, at least 80% of the known positive lesions on 123I-MIBG imaging is visualized. | 20 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normal-organ and tumor uptake of 18F-MFBG as a function of time | Patients will undergo dynamic PET scanning followed by three static whole-body PET/CT scans at different time points post injection. Uptake as a function of time (pharmacokinetics) will be studied using the software package PMOD (PMOD technologies LLC, Zürich, Switzerland). Volumes of interest (VOIs) will be delineated in relevant normal organs and tumor lesions on all PET images and standardized uptake values (SUV) in all these VOIs will be measured to compute normal-organ and tumor uptake as a function of time. | 20 months |
| Identify the ideal time point for imaging after 18F-MFBG injection. | Tumor-to-background ratios as a function of time will be measured. The time point resulting in optimal tumor-to-background ratios, taking into account a realistic implementation in clinical practice, will be defined as the ideal time point for imaging. | 20 months |
| Safety analysis of 18F-MFBG administration: Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 | The impact of 18F-MFBG administration on clinical symptoms and signs and biochemistry values will be evaluated. Baseline values will be recorded and subjects will be assessed clinically and with serial biochemical analysis. Adverse events will be scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | 20 months |
| Assessment of lesion targeting by 18F-MFBG as compared to 123I-MIBG | A lesion-by-lesion analysis (visual and semi-quantitative) will be performed to compare the number of detected lesions using both tracers. | 20 months |
|
PET/CT, norepinephrine transporter imaging, 18F-MFBG
|
Neoplasms, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Neoplasms, Nerve Tissue
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients<br>A single dose of 18F-MFBG will be intravenously injected in 10 patients with neural crest tumors or neuroendocrine tumors. Adult patients will first undergo a dynamic PET scan, followed by whole-body PET/CT scans at various time points for a pharmacokinetics study and efficacy assessment. Pediatric patients will undergo, depending on what is feasible for the child, at least 1 and up to 2 static whole-body PET/CTs. In patients 12 years or older, also a dynamic PET scan can be performed. | Drug: (18F)MFBG<br>* One intravenous injection of 4 MBq/kg (adults) One intravenous injection of 2 MBq/kg (minor participants)<br>* Other names: 18F-MFBG;Device: PET/CT<br>* Adult patients will undergo a dynamic PET scan for the first 30 minutes, followed by 3 static whole-body PET/CTs at 60 ± 10 min, 120 ± 30 min and 180 ± 30 min post injection. Pediatric patients will undergo, depending on what is feasible for the child, at least 1 and up to 2 static whole-body PET/CTs. In patients 12 years or older, also a dynamic PET scan can be performed.<br>Other: Venous blood samples<br>* Blood samples will be obtained for laboratory safety evaluation for initial screening and safety evaluation after injection. Furthermore, in patients undergoing a dynamic PET scan venous blood samples will be obtained for metabolite analysis and activity measurements at various time points post injection (5 ± 2 min, 10 ± 5 min, 20 ± 10 min, 40 ± 20 min, 60 ± 30 min and 120 ± 60 min in adult participants; 5 ± 2 min, 10 ± 5 min, 30 ± 15 min, 50 ± 25 min, 90 ± 30 min in minor participants).<br>|
|
18F-MFBG PET Imaging of the Norepinephrine Transporter in Neural Crest and Neuroendocrine Tumors
Study Overview
=================
Brief Summary
-----------------
The aim of this study is to evaluate the potential and feasibility of 18F-metafluorobenzylguanidine (18F-MFBG) positron emission tomography (PET) in patients with neural crest and neuroendocrine tumors.
Detailed Description
-----------------
Ten neural crest tumor or neuroendocrine tumor (NET) patients, with a routine clinical 123I-metaiodobenzylguanidine (123I-MIBG imaging) (planar + single photon emission tomography (SPECT)) performed in the previous six months or scheduled within three months, will undergo a dynamic PET scan for the first 30 minutes, followed by 3 static whole-body PET/CTs up to three hours post injection for a pharmacokinetics study and efficacy assessment of 18F-MFBG in humans. Furthermore, a comparison with 123I-MIBG imaging will be performed.
Official Title
-----------------
18F-MFBG PET Imaging of the Norepinephrine Transporter in Neural Crest and Neuroendocrine Tumors: a Phase I PET/CT Study
Conditions
-----------------
Neural Crest Tumor, Neuroendocrine Tumors
Intervention / Treatment
-----------------
* Drug: (18F)MFBG
* Device: PET/CT
* Other: Venous blood samples
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is aged 1 year or older Signed Informed Consent by the participant (adult) or his/her parents or legal guardian (minors) Subject is diagnosed with a neural crest tumor or neuroendocrine tumor Subject is judged to be in good general condition by the investigator on the basis of medical history, physical examination including vital signs and clinical laboratory tests, besides the diagnosis of a neural crest tumor Subject should have a routine clinical 123I-MIBG scintigraphy (planar + SPECT/CT) performed within 6 months prior to the inclusion visit or scheduled within 3 months after the inclusion visit Adult female subjects should be post-menopausal or surgically sterile or using effective contraceptive with negative pregnancy test. Minor female participants of childbearing potential that are sexually active should be using effective contraceptive with negative pregnancy test Exclusion Criteria: Subject has a previous or ongoing recurrent or chronic disease, other than a neural crest tumor, at high risk to interfere with the evaluation of the trial according to the judgement of the investigator, e.g. known gastro-intestinal, hepatic, renal, cardiovascular, metabolic or hormonal disease, cancer, major neurological or convulsive disorder or any psychiatric disease Subject is currently, or within two weeks prior to the inclusion visit, a user (including ''recreational use'') of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse Subject is unable to refrain from smoking more than 10 cigarettes per day during the study Subject has had exposure to ionizing radiation (> 1 mSv) in other research studies within the last 12 months Subject suffers from claustrophobia or cannot tolerate confinement during PET/CT scanning procedures Adult subject cannot lie still for 45 minutes inside the scanner. Minor participant cannot lie still for the duration of at least one whole-body PET/CT, varying from 15 to 30 minutes depending on the length of the child, except for children who will be sedated for one scan Subject is unwilling to avoid unusual, unaccustomed, or strenuous physical activity (i.e. weight lifting, running, bicycling) from the time of the selection visit until the final safety telephone follow-up interview Subject or his/her parents or legal guardian in case of minors, does not understand the study procedure Subject is unwilling or unable to perform all of the study procedures, or is considered unsuitable in any way by the principal investigator. Subject is potentially pregnant (serum and urinary hCG test will be performed in women where pregnancy is not excluded) or is breast-feeding Subject has recently (< 30 days or 5 times the plasma half-life of the investigated drug, whichever is longest) participated or is simultaneously participating in another prospective interventional clinical trial Subject has a history of multiple and/or severe allergies to drugs or food Subject underwent surgery between the selection and inclusion visit Adult subject is mentally or legally incapacitated
Ages Eligible for Study
-----------------
Minimum Age: 1 Year
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: Patients<br>A single dose of 18F-MFBG will be intravenously injected in 10 patients with neural crest tumors or neuroendocrine tumors. Adult patients will first undergo a dynamic PET scan, followed by whole-body PET/CT scans at various time points for a pharmacokinetics study and efficacy assessment. Pediatric patients will undergo, depending on what is feasible for the child, at least 1 and up to 2 static whole-body PET/CTs. In patients 12 years or older, also a dynamic PET scan can be performed. | Drug: (18F)MFBG<br>* One intravenous injection of 4 MBq/kg (adults) One intravenous injection of 2 MBq/kg (minor participants)<br>* Other names: 18F-MFBG;Device: PET/CT<br>* Adult patients will undergo a dynamic PET scan for the first 30 minutes, followed by 3 static whole-body PET/CTs at 60 ± 10 min, 120 ± 30 min and 180 ± 30 min post injection. Pediatric patients will undergo, depending on what is feasible for the child, at least 1 and up to 2 static whole-body PET/CTs. In patients 12 years or older, also a dynamic PET scan can be performed.<br>Other: Venous blood samples<br>* Blood samples will be obtained for laboratory safety evaluation for initial screening and safety evaluation after injection. Furthermore, in patients undergoing a dynamic PET scan venous blood samples will be obtained for metabolite analysis and activity measurements at various time points post injection (5 ± 2 min, 10 ± 5 min, 20 ± 10 min, 40 ± 20 min, 60 ± 30 min and 120 ± 60 min in adult participants; 5 ± 2 min, 10 ± 5 min, 30 ± 15 min, 50 ± 25 min, 90 ± 30 min in minor participants).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmation of 18F-MFBG as a hNET imaging agent in patients with neural crest and neuroendocrine tumors. | The primary endpoint will be met if in 8 out of 10 patients, at least 80% of the known positive lesions on 123I-MIBG imaging is visualized. | 20 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normal-organ and tumor uptake of 18F-MFBG as a function of time | Patients will undergo dynamic PET scanning followed by three static whole-body PET/CT scans at different time points post injection. Uptake as a function of time (pharmacokinetics) will be studied using the software package PMOD (PMOD technologies LLC, Zürich, Switzerland). Volumes of interest (VOIs) will be delineated in relevant normal organs and tumor lesions on all PET images and standardized uptake values (SUV) in all these VOIs will be measured to compute normal-organ and tumor uptake as a function of time. | 20 months |
| Identify the ideal time point for imaging after 18F-MFBG injection. | Tumor-to-background ratios as a function of time will be measured. The time point resulting in optimal tumor-to-background ratios, taking into account a realistic implementation in clinical practice, will be defined as the ideal time point for imaging. | 20 months |
| Safety analysis of 18F-MFBG administration: Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 | The impact of 18F-MFBG administration on clinical symptoms and signs and biochemistry values will be evaluated. Baseline values will be recorded and subjects will be assessed clinically and with serial biochemical analysis. Adverse events will be scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. | 20 months |
| Assessment of lesion targeting by 18F-MFBG as compared to 123I-MIBG | A lesion-by-lesion analysis (visual and semi-quantitative) will be performed to compare the number of detected lesions using both tracers. | 20 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PET/CT, norepinephrine transporter imaging, 18F-MFBG
|
NCT03280745
|
Hypertonic Saline for Fluid Resuscitation After Cardiac Surgery
|
Background: Volume replacement strategies and type of fluid used in patients undergoing cardiac surgery have changed during the last years. Currently used crystalloid solutes have a variable composition and a major impact on organ function and outcome. Additionally critically ill patients are prone to fluid overload, which is despite common perception, not a benign occurrence as it is associated with prolonged ICU- and hospital length of stay and increased mortality rates. Fluid resuscitation using bolus or continuous infusion of hypertonic saline was used for more than thirty years. Only a few studies have been conducted so far, but they showed that infusion of hypertonic saline results in less volume administered, increased renal function less weight gain in critically ill patients when compared to other crystalloids.~Aim: This preliminary randomized controlled double-blind study aims to identify whether fluid resuscitation using hypertonic saline (HS) when used in addition to lactated Ringers solution results in less total fluid amount administered in patients following cardiac surgery. Additionally we want to evaluate whether the use of hypertonic saline results less need for pharmacological cardiocirculatory support, increased renal function, less postoperative volume overload shortened post-cardiac bypass immune suppression and increased postoperative outcomes.~Study intervention: At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl or 0.9% NaCl by infusion pump over 60 minutes. If necessary, fluid resuscitation will thereafter be performed with Ringer's lactate to normalize peripheral perfusion and to allow weaning of vasopressors.
|
Hypertonic Saline for Fluid Resuscitation After Cardiac Surgery
|
Cardiovascular Diseases, Valvular Heart Disease
|
* Drug: Hypertonic saline
* Drug: 0.9% saline
|
Inclusion Criteria:~Adult patients undergoing cardiac surgery for ischemic or valvular heart disease~Exclusion Criteria:~Patients unable to give informed consent~Patients with age <18 years~Pregnancy or breastfeeding~Left-ventricular ejection fraction (LVEF) < 30% preoperatively~Preexisting renal insufficiency with an eGFR <30 ml/min/1.73m2~Patients with postoperative circulatory support devices such as LVAD, IABP, Impella, ECMO~Preexisting serum sodium of >145mmol/l or <135 mmol/L~Preexisting serum chloremia >107mmol/l or < 98 mmol/L~Systemic steroid therapy (at any dose at time of inclusion)~Chronic liver disease (bilirubin >3 mg.dl)~Any signs of infection or sepsis defined as clear clinical evidence for active infection or current antibiotic therapy
|
18 Years
| null |
All
|
No
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl or 0.9% NaCl by infusion pump over 60 minutes. If necessary, fluid resuscitation will be performed with Ringer's lactate to normalize peripheral perfusion and to allow weaning of vasopressors.
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total cumulative amount of fluids infused | | daily until ICU discharge, max until postoperative day 90 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative weight gain | | until postoperative day 6 |
| total postoperative cumulative urinary output | | daily until ICU discharge, max until postoperative day 90 |
| total cumulative dose of inopressors per kg bodyweight /hour | cumulation of norepinephrine and epinephrine | until ICU discharge, max until postoperative day 90 |
| time on inopressors | norepinephrine and/or epinephrine | from ICU admission until stop of inopressors, max until postoperative day 90 |
| variation in renal function markers | renal damage maker (TIMP2-IGFB, creatinine) | until postoperative day 6 |
| variation in acid-base homeostasis | pH, base excess, lactate, bicarbonate, electrolytes | until postoperative day 6 |
| variation in immune function | mHLA-DR | until postoperative day 6 |
| time on the ventilator | | from ICU admission until time of extubation, maximum 90 days |
| occurence of infection | | occurence of infection during the index hospitalisation or subsequent admissions due to infection upto 90 postoperative days |
| length of stay | time to ICU/hospital-discharge | time to ICU/hospital-discharge however long this may take, maximum 90 days |
| readmissions to the ICU | | readmissions to the ICU within postoperative 90 days |
| mortality | | until postoperative day 90 |
|
Cardiovascular Diseases, Heart Diseases, Heart Valve Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 7.3% NaCl (intervention)<br>At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl NaCl by infusion pump over 60 minutes. | Drug: Hypertonic saline<br>* At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl by infusion pump over 60 minutes.<br>* Other names: 7.9% NaCl;|
| Active Comparator: 0.9% NaCl (comparator)<br>At admission to the ICU patients will receive 5ml/kg body weight of 0.9% NaCl by infusion pump over 60 minutes. | Drug: 0.9% saline<br>* At admission to the ICU patients will receive 5ml/kg body weight of 0.9% NaCl by infusion pump over 60 minutes.<br>* Other names: normal saline;|
|
Hypertonic Saline for Fluid Resuscitation After Cardiac Surgery
Study Overview
=================
Brief Summary
-----------------
Background: Volume replacement strategies and type of fluid used in patients undergoing cardiac surgery have changed during the last years. Currently used crystalloid solutes have a variable composition and a major impact on organ function and outcome. Additionally critically ill patients are prone to fluid overload, which is despite common perception, not a benign occurrence as it is associated with prolonged ICU- and hospital length of stay and increased mortality rates. Fluid resuscitation using bolus or continuous infusion of hypertonic saline was used for more than thirty years. Only a few studies have been conducted so far, but they showed that infusion of hypertonic saline results in less volume administered, increased renal function less weight gain in critically ill patients when compared to other crystalloids. Aim: This preliminary randomized controlled double-blind study aims to identify whether fluid resuscitation using hypertonic saline (HS) when used in addition to lactated Ringers solution results in less total fluid amount administered in patients following cardiac surgery. Additionally we want to evaluate whether the use of hypertonic saline results less need for pharmacological cardiocirculatory support, increased renal function, less postoperative volume overload shortened post-cardiac bypass immune suppression and increased postoperative outcomes. Study intervention: At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl or 0.9% NaCl by infusion pump over 60 minutes. If necessary, fluid resuscitation will thereafter be performed with Ringer's lactate to normalize peripheral perfusion and to allow weaning of vasopressors.
Official Title
-----------------
Hypertonic Saline for Fluid Resuscitation After Cardiac Surgery
Conditions
-----------------
Cardiovascular Diseases, Valvular Heart Disease
Intervention / Treatment
-----------------
* Drug: Hypertonic saline
* Drug: 0.9% saline
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients undergoing cardiac surgery for ischemic or valvular heart disease Exclusion Criteria: Patients unable to give informed consent Patients with age <18 years Pregnancy or breastfeeding Left-ventricular ejection fraction (LVEF) < 30% preoperatively Preexisting renal insufficiency with an eGFR <30 ml/min/1.73m2 Patients with postoperative circulatory support devices such as LVAD, IABP, Impella, ECMO Preexisting serum sodium of >145mmol/l or <135 mmol/L Preexisting serum chloremia >107mmol/l or < 98 mmol/L Systemic steroid therapy (at any dose at time of inclusion) Chronic liver disease (bilirubin >3 mg.dl) Any signs of infection or sepsis defined as clear clinical evidence for active infection or current antibiotic 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl or 0.9% NaCl by infusion pump over 60 minutes. If necessary, fluid resuscitation will be performed with Ringer's lactate to normalize peripheral perfusion and to allow weaning of vasopressors.
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 7.3% NaCl (intervention)<br>At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl NaCl by infusion pump over 60 minutes. | Drug: Hypertonic saline<br>* At admission to the ICU patients will receive 5ml/kg body weight of 7.3% NaCl by infusion pump over 60 minutes.<br>* Other names: 7.9% NaCl;|
| Active Comparator: 0.9% NaCl (comparator)<br>At admission to the ICU patients will receive 5ml/kg body weight of 0.9% NaCl by infusion pump over 60 minutes. | Drug: 0.9% saline<br>* At admission to the ICU patients will receive 5ml/kg body weight of 0.9% NaCl by infusion pump over 60 minutes.<br>* Other names: normal saline;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total cumulative amount of fluids infused | | daily until ICU discharge, max until postoperative day 90 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative weight gain | | until postoperative day 6 |
| total postoperative cumulative urinary output | | daily until ICU discharge, max until postoperative day 90 |
| total cumulative dose of inopressors per kg bodyweight /hour | cumulation of norepinephrine and epinephrine | until ICU discharge, max until postoperative day 90 |
| time on inopressors | norepinephrine and/or epinephrine | from ICU admission until stop of inopressors, max until postoperative day 90 |
| variation in renal function markers | renal damage maker (TIMP2-IGFB, creatinine) | until postoperative day 6 |
| variation in acid-base homeostasis | pH, base excess, lactate, bicarbonate, electrolytes | until postoperative day 6 |
| variation in immune function | mHLA-DR | until postoperative day 6 |
| time on the ventilator | | from ICU admission until time of extubation, maximum 90 days |
| occurence of infection | | occurence of infection during the index hospitalisation or subsequent admissions due to infection upto 90 postoperative days |
| length of stay | time to ICU/hospital-discharge | time to ICU/hospital-discharge however long this may take, maximum 90 days |
| readmissions to the ICU | | readmissions to the ICU within postoperative 90 days |
| mortality | | until postoperative day 90 |
|
||
NCT05596019
|
Specific Neurodynamic Exercises on Disability and Neck Pain in Old Women
|
This is a randomized, parallel, double-blind clinical trial. The main objective is to compare the efficacy of multimodal exercise with specific neurodynamic exercises and multimodal exercise with non-specific exercises in disability and neck pain in women older than 65 years.~The intervention in both groups will be carried out for 4 weeks, with three weekly sessions. Two evaluations will be carried out, a pre-intervention evaluation and a post-intervention evaluation. We will assess neck pain, disability, upper limb strength, cervical mobility, cervical pressure pain thresholds, kinesiophobia and catastrophism.
|
Effectiveness of Specific Neurodynamic Exercises Compared With Non-specific Exercises on Disability and Neck Pain in Women Older Than 65 Years
|
Neck Pain
|
* Procedure: specific neurodynamic exercises
* Procedure: multimodal exercise
|
Inclusion Criteria:~Women older than 65 years.~Neck pain~Exclusion Criteria:~Tumors~Pacemakers~Fibrillations~Cardiac pathology or uncontrolled hypertension~History of severe trauma/recent cervical surgery~Uncontrolled systemic and inflammatory pathologies~Congenital collagen compromise~Presence of difficulties in performing the Initial Evaluation tests~Language barriers~Pending litigation or legal claim
|
65 Years
| null |
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Longitudinal prospective, controlled, single-blind study
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Numerical Pain Rating Scale (NPRS) will be used. It is a scale used to quantify the patient's pain level on an 11-point numerical scale 0-10 with 0 being no pain and 10 being the worst possible pain. | four weeks. |
| Neck disability | The Neck Disability Index (NDI) will be used. It is a modification of the Oswestry Low Back Pain Disability Index. It is a scale used to measure disability associated with cervical pain due to acute or chronic conditions. He has 10 items: 7 related to activities of daily living, 2 related to pain and 1 related to concentration. The test can be interpreted with a maximum score of 50. | four weeks |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cervical range of motion | The Cervical Range of Motion (CROM) device (Performance Attainment Associates, USA) will be used to measure the cervical range of motion, including flexion, extension, lateral flexion and rotation. | four weeks |
| Hand grip strength | The strength will be recorded with Jamar Plus: Digital dynamometer to assess grip strength. | four weeks |
| upper limb strength | The strength in upper limb movements will be recorded with the device wireless MicroFET 2: Hand-held dynamometer for force assessment. | four weeks |
| Pressure pain threshold | Pressure algometry measurements will be performed with a digital algometer to assess pressure pain thresholds. (Algometer model: Pain Test™ FPIX 10). | four weeks |
| Kinesiophobia | The Tampa Scale for kinesiophobia (TSK-13) will be used. It is a patient-reported outcome measure designed to help identify kinesiophobia. This version is a 13-item questionnaire aimed at the assessment of fear of movement/re-injury. Each item is provided with a 4-points Likert scale with scoring alternatives ranging from strongly disagree [0] to strongly agree [4] . This gives a possible total raw score range from 0 to 52. | four weeks |
| Catastrophism | Pain Catastrophizing Scale (PCS) will be used. People are asked to indicate the degree to which they have the above thoughts and feelings when they are experiencing pain using the 0 (not at all) to 4 (all the time) scale. A total score is yielded (ranging from 0-52). | four weeks |
|
exercise, neck pain, neurodynamic, elderly
|
Pain, Neck Pain, Neurologic Manifestations
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: neurodynamics specific exercise group<br>The experimental group will perform a multimodal therapeutic physical exercise program. The components of balance, walking, cardiovascular endurance, strength and flexibility will be worked globally, in addition to including respiratory exercises.~Specific neurodynamic exercises oriented to the treatment of the main nerves of the brachial plexus will be included as part of the exercise sessions. The specific neurodynamic program will consist of the following exercises:~Opening of the cervical conjunction holes with cranio-cervical and cervical flexion movements, cervical lateroflexions and lateral vertebral sliding self-mobilizations.~Opening of the thoracic passages of the brachial plexus with stretching of the scalene muscles, opening of the costoclavicular space and stretching of the pectoralis minor muscles.~Specific exercises of neurodynamic sliding of the nerves of the upper limb: median, radial and ulnar nerves. | Procedure: specific neurodynamic exercises<br>* Specific neurodynamic exercises in women older than 65 years with neck pain<br>|
| Active Comparator: The nonspecific exercise group<br>The nonspecific exercise group performed balance, cardiovascular endurance, stability, upper and lower limb strength, flexibility, and breathing exercises. | Procedure: multimodal exercise<br>* Multimodal and nonspecific exercises in women older than 65 years with neck pain<br>|
|
Specific Neurodynamic Exercises on Disability and Neck Pain in Old Women
Study Overview
=================
Brief Summary
-----------------
This is a randomized, parallel, double-blind clinical trial. The main objective is to compare the efficacy of multimodal exercise with specific neurodynamic exercises and multimodal exercise with non-specific exercises in disability and neck pain in women older than 65 years. The intervention in both groups will be carried out for 4 weeks, with three weekly sessions. Two evaluations will be carried out, a pre-intervention evaluation and a post-intervention evaluation. We will assess neck pain, disability, upper limb strength, cervical mobility, cervical pressure pain thresholds, kinesiophobia and catastrophism.
Official Title
-----------------
Effectiveness of Specific Neurodynamic Exercises Compared With Non-specific Exercises on Disability and Neck Pain in Women Older Than 65 Years
Conditions
-----------------
Neck Pain
Intervention / Treatment
-----------------
* Procedure: specific neurodynamic exercises
* Procedure: multimodal exercise
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women older than 65 years. Neck pain Exclusion Criteria: Tumors Pacemakers Fibrillations Cardiac pathology or uncontrolled hypertension History of severe trauma/recent cervical surgery Uncontrolled systemic and inflammatory pathologies Congenital collagen compromise Presence of difficulties in performing the Initial Evaluation tests Language barriers Pending litigation or legal claim
Ages Eligible for Study
-----------------
Minimum Age: 65 Years
Sexes Eligible for Study
-----------------
Female
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: Longitudinal prospective, controlled, single-blind study
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: neurodynamics specific exercise group<br>The experimental group will perform a multimodal therapeutic physical exercise program. The components of balance, walking, cardiovascular endurance, strength and flexibility will be worked globally, in addition to including respiratory exercises. Specific neurodynamic exercises oriented to the treatment of the main nerves of the brachial plexus will be included as part of the exercise sessions. The specific neurodynamic program will consist of the following exercises: Opening of the cervical conjunction holes with cranio-cervical and cervical flexion movements, cervical lateroflexions and lateral vertebral sliding self-mobilizations. Opening of the thoracic passages of the brachial plexus with stretching of the scalene muscles, opening of the costoclavicular space and stretching of the pectoralis minor muscles. Specific exercises of neurodynamic sliding of the nerves of the upper limb: median, radial and ulnar nerves. | Procedure: specific neurodynamic exercises<br>* Specific neurodynamic exercises in women older than 65 years with neck pain<br>|
| Active Comparator: The nonspecific exercise group<br>The nonspecific exercise group performed balance, cardiovascular endurance, stability, upper and lower limb strength, flexibility, and breathing exercises. | Procedure: multimodal exercise<br>* Multimodal and nonspecific exercises in women older than 65 years with neck pain<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Numerical Pain Rating Scale (NPRS) will be used. It is a scale used to quantify the patient's pain level on an 11-point numerical scale 0-10 with 0 being no pain and 10 being the worst possible pain. | four weeks. |
| Neck disability | The Neck Disability Index (NDI) will be used. It is a modification of the Oswestry Low Back Pain Disability Index. It is a scale used to measure disability associated with cervical pain due to acute or chronic conditions. He has 10 items: 7 related to activities of daily living, 2 related to pain and 1 related to concentration. The test can be interpreted with a maximum score of 50. | four weeks |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cervical range of motion | The Cervical Range of Motion (CROM) device (Performance Attainment Associates, USA) will be used to measure the cervical range of motion, including flexion, extension, lateral flexion and rotation. | four weeks |
| Hand grip strength | The strength will be recorded with Jamar Plus: Digital dynamometer to assess grip strength. | four weeks |
| upper limb strength | The strength in upper limb movements will be recorded with the device wireless MicroFET 2: Hand-held dynamometer for force assessment. | four weeks |
| Pressure pain threshold | Pressure algometry measurements will be performed with a digital algometer to assess pressure pain thresholds. (Algometer model: Pain Test™ FPIX 10). | four weeks |
| Kinesiophobia | The Tampa Scale for kinesiophobia (TSK-13) will be used. It is a patient-reported outcome measure designed to help identify kinesiophobia. This version is a 13-item questionnaire aimed at the assessment of fear of movement/re-injury. Each item is provided with a 4-points Likert scale with scoring alternatives ranging from strongly disagree [0] to strongly agree [4] . This gives a possible total raw score range from 0 to 52. | four weeks |
| Catastrophism | Pain Catastrophizing Scale (PCS) will be used. People are asked to indicate the degree to which they have the above thoughts and feelings when they are experiencing pain using the 0 (not at all) to 4 (all the time) scale. A total score is yielded (ranging from 0-52). | four weeks |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
exercise, neck pain, neurodynamic, elderly
|
|
NCT03849729
|
Effectiveness and Tolerability of Phentermine in Patients Under Bariatric Surgery
|
Surgical management of Morbid Obesity is increasingly frequent. A low-calorie diet is recommended with the main goal of reducing intrahepatic fat infiltration, fat tissue and making easier the surgery. Information the use pharmacological interventions during the preoperative period in this population are rare.
|
This is a randomized, control trial to investigate the effect and safety of Phentermine in patients with obesity who need a bariatric surgery (BMI >35 kg/m2 with comorbidities or BMI > 40 kg/m2).~Screening will be made to select eligible participants before intervention. Participants were randomly assigned to one of two groups (low-calorie diet + phentermine 15 mg or low-calorie diet + placebo) for therapies during 6 weeks. Anthropometric measurements (weight, body composition, body mass index and waist-hip index), serum metabolic profile (glucose, total cholesterol, HDL-c, LDL-c, triglycerides, and HOMA-IR) markers of inflammation (IL-1, IL-6 and PCR) and hepatic ultrasound will be measured 2 times for each participant. Surgical complications (anastomosis filtration, intestinal obstruction or stenosis, need to perform open surgery and mortality) will be evaluated. Adverse events associated with phentermine (blood pressure, cardiac frequency, headache, gastrointestinal symptoms, euphoria, anxiety and insomnia) will be collected.
|
Effectiveness and Tolerability of Phentermine in the Reduction of Intrahepatic Fat Infiltration, Adipose Tissue and Postoperative Complications in Patients Under Bariatric Surgery
|
Obesity, Morbid Obesity, Bariatric Surgery, Non-alcoholic Fatty Liver, Weight Loss
|
* Drug: Phentermine
* Other: Placebo
|
Inclusion Criteria:~Women and men~>18 years and <55 years old.~Diagnosis of obesity grade II with comorbidities~Diagnosis of obesity grade III with or without comorbidities~Approved to bariatric surgery by an interdisciplinary committee~Having signed the Informed consent form~Exclusion Criteria:~Use of addictive substances~Inability or lack of understanding to achieve lifestyle and behaviour changes~Mental disease~Severe Pulmonary disease~Giant Hiatal hernia, gastric or duodenal ulcer~Unstable coronary artery disease~Portal hypertension or esophageal varices~Surgical or anesthetic high risk
|
18 Years
|
55 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental, analytic, comparative, prospective, longitudinal and double-blinded study.
Masking: Triple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Intrahepatic fat | Intrahepatic fat semi-qualitative asessment: mild(<20%), moderate (20-30%), severe (>30%) | Change from baseline after 6 weeks treatment based on hepatic ultrasound. |
| Fat tissue | Fat tissue: fat mass in Kilograms and percentage | change from baseline after 6 weeks treatment based on body composition by bioimpedance |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic profile | Changes in serum metabolic profile: mg/dL | Change from baseline after 6 weeks treatment based on glucose, total cholesterol, HDL-c, LDL-c, triglycerides, and HOMA-IR. |
| Markers of inflammation | Changes in serum markers of inflammation: pg/mL | Change from baseline after 6 weeks treatment based on IL-1, IL-6 and PCR |
| Surgical complications | Prevalence of surgical complications (yes or no): 1) dehiscence of anastomosis, 2) intestinal obstruction, 3) intestinal stenosis | Surgical complications during hospitalization and up to 30 days after surgery 1) dehiscence of anastomosis, 2) intestinal obstruction, 3) intestinal stenosis |
| Adverse events associated with phentermine | Determine the frequency and severity of adverse events | Adverse events during and the end of 6-8 weeks of phentermine (blood pressure, cardiac frequency, headache, gastrointestinal symptoms, euphoria, anxiety and insomnia) associated with phentermine. |
|
Obesity, Obesity treatment, Non-alcoholic Fatty Liver, Weight Loss
|
Phentermine, Central Nervous System Stimulants, Physiological Effects of Drugs, Appetite Depressants, Anti-Obesity Agents, Sympathomimetics, Autonomic Agents, Peripheral Nervous System Agents, Adrenergic Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phentermine<br>Low-calorie diet + Phentermine Capsules 15 mg po by 6 weeks, one time a day before bariatric surgery. | Drug: Phentermine<br>* This is a randomized, control trial to investigate the effect and safety of Phentermine in patients with obesity who need a bariatric surgery (BMI >35 kg/m2 with comorbidities or BMI > 40 kg/m2).<br>* Other names: Terfamex;|
| Placebo Comparator: Placebo<br>Low-calorie diet + Placebo Capsules po by 6 weeks, one time a day before bariatric surgery. | Other: Placebo<br>* his is a randomized, control trial to investigate the effect and safety of Phentermine in patients with obesity who need a bariatric surgery (BMI >35 kg/m2 with comorbidities or BMI > 40 kg/m2).<br>|
|
Effectiveness and Tolerability of Phentermine in Patients Under Bariatric Surgery
Study Overview
=================
Brief Summary
-----------------
Surgical management of Morbid Obesity is increasingly frequent. A low-calorie diet is recommended with the main goal of reducing intrahepatic fat infiltration, fat tissue and making easier the surgery. Information the use pharmacological interventions during the preoperative period in this population are rare.
Detailed Description
-----------------
This is a randomized, control trial to investigate the effect and safety of Phentermine in patients with obesity who need a bariatric surgery (BMI >35 kg/m2 with comorbidities or BMI > 40 kg/m2). Screening will be made to select eligible participants before intervention. Participants were randomly assigned to one of two groups (low-calorie diet + phentermine 15 mg or low-calorie diet + placebo) for therapies during 6 weeks. Anthropometric measurements (weight, body composition, body mass index and waist-hip index), serum metabolic profile (glucose, total cholesterol, HDL-c, LDL-c, triglycerides, and HOMA-IR) markers of inflammation (IL-1, IL-6 and PCR) and hepatic ultrasound will be measured 2 times for each participant. Surgical complications (anastomosis filtration, intestinal obstruction or stenosis, need to perform open surgery and mortality) will be evaluated. Adverse events associated with phentermine (blood pressure, cardiac frequency, headache, gastrointestinal symptoms, euphoria, anxiety and insomnia) will be collected.
Official Title
-----------------
Effectiveness and Tolerability of Phentermine in the Reduction of Intrahepatic Fat Infiltration, Adipose Tissue and Postoperative Complications in Patients Under Bariatric Surgery
Conditions
-----------------
Obesity, Morbid Obesity, Bariatric Surgery, Non-alcoholic Fatty Liver, Weight Loss
Intervention / Treatment
-----------------
* Drug: Phentermine
* Other: Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women and men >18 years and <55 years old. Diagnosis of obesity grade II with comorbidities Diagnosis of obesity grade III with or without comorbidities Approved to bariatric surgery by an interdisciplinary committee Having signed the Informed consent form Exclusion Criteria: Use of addictive substances Inability or lack of understanding to achieve lifestyle and behaviour changes Mental disease Severe Pulmonary disease Giant Hiatal hernia, gastric or duodenal ulcer Unstable coronary artery disease Portal hypertension or esophageal varices Surgical or anesthetic high risk
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 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: Experimental, analytic, comparative, prospective, longitudinal and double-blinded study.
Masking: Triple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phentermine<br>Low-calorie diet + Phentermine Capsules 15 mg po by 6 weeks, one time a day before bariatric surgery. | Drug: Phentermine<br>* This is a randomized, control trial to investigate the effect and safety of Phentermine in patients with obesity who need a bariatric surgery (BMI >35 kg/m2 with comorbidities or BMI > 40 kg/m2).<br>* Other names: Terfamex;|
| Placebo Comparator: Placebo<br>Low-calorie diet + Placebo Capsules po by 6 weeks, one time a day before bariatric surgery. | Other: Placebo<br>* his is a randomized, control trial to investigate the effect and safety of Phentermine in patients with obesity who need a bariatric surgery (BMI >35 kg/m2 with comorbidities or BMI > 40 kg/m2).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Intrahepatic fat | Intrahepatic fat semi-qualitative asessment: mild(<20%), moderate (20-30%), severe (>30%) | Change from baseline after 6 weeks treatment based on hepatic ultrasound. |
| Fat tissue | Fat tissue: fat mass in Kilograms and percentage | change from baseline after 6 weeks treatment based on body composition by bioimpedance |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic profile | Changes in serum metabolic profile: mg/dL | Change from baseline after 6 weeks treatment based on glucose, total cholesterol, HDL-c, LDL-c, triglycerides, and HOMA-IR. |
| Markers of inflammation | Changes in serum markers of inflammation: pg/mL | Change from baseline after 6 weeks treatment based on IL-1, IL-6 and PCR |
| Surgical complications | Prevalence of surgical complications (yes or no): 1) dehiscence of anastomosis, 2) intestinal obstruction, 3) intestinal stenosis | Surgical complications during hospitalization and up to 30 days after surgery 1) dehiscence of anastomosis, 2) intestinal obstruction, 3) intestinal stenosis |
| Adverse events associated with phentermine | Determine the frequency and severity of adverse events | Adverse events during and the end of 6-8 weeks of phentermine (blood pressure, cardiac frequency, headache, gastrointestinal symptoms, euphoria, anxiety and insomnia) associated with phentermine. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Obesity, Obesity treatment, Non-alcoholic Fatty Liver, Weight Loss
|
NCT03633149
|
Choices4Health: Intervention to Prevent Substance-exposed Pregnancy
|
This is a 4-year randomized, controlled study to test the efficacy of the CHOICES4Health-T (C4H-T) delivered by a computerized tablet, CHOICES4Health-C (C4H-C), delivered by a counselor, and brief advice (BA), on reducing preconception substance-exposed pregnancy risk (i.e. drinking below risk levels; tobacco and marijuana cessation; effective contraception use) among women (aged 18-44) presenting to the 13 primary care clinics that serve adults within the Harris Health System. Given the natural fit between contraceptive and HIV prevention counseling the CHOICES4Health interventions will also target HIV sexual risk behaviors.
|
A randomized group design (N = 240) will be used to test the efficacy of the C4H-C and C4H-T interventions relative to Brief Advice (BA) to reduce the risk of substance-exposed pregnancy) SEP in preconception women of childbearing age. Follow-up assessments will be conducted at 3, 6, and 9 months.~Each of the substances targeted in this study (risk drinking, cigarette smoking, and marijuana use) is commonly used relative to other substances and is singly or jointly associated with risk for poor fetal outcomes. Thus, women who are not using effective contraception (i.e., use of effective birth-control methods during all vaginal intercourse) and have any one or more substance-risk behaviors in the 30 days before intake will be eligible for the study.~Urn randomization will be used to stratify women on all three substance-risk behaviors to ensure a balanced number of women presenting with alcohol-exposed pregnancy (AEP), tobacco-exposed pregnancy (TEP), and marijuana-exposed pregnancy (MEP) risks across the three study conditions. To address risk distribution for women who present with more than one risk behavior the urn randomization will also be programmed to balance single risk and multiple risk women across the study conditions. In sum, the urn randomization will include four assignment criteria: AEP, TEP, MEP, and multiple risks. Finally, different numbers of women will be needed for each type of substance-exposed pregnancy risk in order to provide sufficient power for the investigator's analytic tests. For example, approximately 25% more women at risk of AEP are required than for TEP to attain the same power. The investigators will include over sampling rules and stopping rules to ensure adequate recruitment for AEP, TEP, and MEP.
|
Tablet-based Intervention to Prevent Substance-exposed Pregnancy in Primary Care
|
Prenatal Alcohol Exposure, Prenatal Tobacco Exposure, Prenatal Marijuana Exposure
|
* Behavioral: Computer tablet-delivered C4H
* Behavioral: Person-delivered C4H
* Behavioral: Brief Advice
|
Inclusion Criteria: Women who:~are 18-44 years old;~have no condition causing infertility (e.g., tubal ligation, hysterectomy, menopause);~are not pregnant or planning to become pregnant in the next 12 months;~are available for the follow-up period;~had vaginal intercourse during the previous 30 days with a fertile man and did not use effective contraception every time AND are drinking at risk levels (more than 3 drinks/day or more than 7 drinks/week); OR are reporting marijuana use in the previous month, OR are currently smoking cigarettes (at least weekly use) during the 30-day baseline period.~Exclusion Criteria: Women who:~have severe cognitive, and/or psychiatric impairment that precludes cooperation with study protocol, per judgment of the C4H interventionist or research staff;~are unable to read, write, and speak English or Spanish;~are unable or unwilling to meet study requirements, including followup assessments.
|
18 Years
|
44 Years
|
Female
|
Accepts Healthy Volunteers
|
Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in risk of alcohol-exposed pregnancy (AEP) as measured by self-reported daily standard drinks, vaginal sex, and use of contraception on the Timeline Followback calendar. | Risk of AEP is defined as any risk drinking (>3 drinks/day or >7 drinks/week on average) and any occurrence of vaginal sex with no use or ineffective use of contraception in the assessment period. Self-reported daily alcohol use (in standard drinks), vaginal intercourse, and contraception (effective use) data from the Timeline Followback will be used to calculate risk of AEP for the previous 90 days. Change in Risk of AEP will be examined at 3-, 6-, and 9-months post-intake. A participant will be considered at risk of AEP at each of the 3-, 6-, and 9 month timepoints if the participant had any occurrence of vaginal sex without the use of effective contraception and had more than 3 standard drinks on any day or more than 7 standard drinks per week on average in any 30 day period in the previous 90 days. Risk of AEP will be a dichotomous outcome (at risk of AEP or at reduced risk of AEP). | 3, 6, and 9 months |
| Change in risk of tobacco-exposed pregnancy (TEP) as measured by self-reported daily number of cigarettes, vaginal sex, and use of contraception on the Timeline Followback calendar. | Risk of TEP is defined as currently smoking cigarettes (at least weekly use) and any occurrence of vaginal sex with no use or ineffective use of contraception in the assessment period. Self-reported data from the Timeline Followback will be used to calculate risk of TEP for the previous 90 days at 3-, 6 , and 9 months post-intake. A participant will be considered at risk of TEP at each of the 3-, 6-, and 9 month timepoints if the participant had any occurrence of vaginal sex without the use of effective contraception and she had at least weekly smoking in any 30 day period in the previous 90 days. Risk of TEP will be a dichotomous outcome (at risk of TEP or at reduced risk of TEP). | 3, 6, and 9 months |
| Change in risk of marijuana-exposed pregnancy (MEP) as measured by self-reported marijuana use, vaginal sex, and use of contraception on the Timeline Followback calendar. | Risk of MEP is defined as any day with marijuana use and any occurrence of vaginal sex with no use or ineffective use of contraception in the assessment period. Self-reported data from the Timeline Followback will be used to calculate risk of MEP for the previous 90 days at 3-, 6- , and 9 months post-intake. A participant will be considered at risk of MEP at each of the 3-, 6-, and 9 month timepoints if the participant had any occurrence of vaginal sex without the use of effective contraception and had any day with marijuana use in any 30 day period in the previous 90 days. Risk of MEP will be a dichotomous outcome (at risk of MEP or at reduced risk of MEP). | 3, 6, and 9 months |
| Change in risk drinking as measured by self-reported number of standard drinks on the Timeline Followback calendar. | Risk drinking is defined as drinking more than 3 standard drinks on any day or drinking more than 7 standard drinks in a week on average in the previous 90 days. Self-reported data from the Timeline Followback will be used to calculate risk drinking for the previous 90 days at 3-, 6-, and 9-months post-intake. Risk drinking will be a dichotomous outcome (yes or no). | 3, 6, and 9 months |
| Change in cigarette smoking as measured by self-reported number of cigarettes smoked each day on the Timeline Followback calendar. | Cigarette smoking is defined as at least weekly cigarette smoking in the previous 90 days on the Timeline Followback calendar at 3-, 6-, and 9-months post-intake. Cigarette smoking will be a dichotomous outcome (yes or no). In addition, smoking will be validated using biological test to assess cotinine levels. | 3, 6, and 9 months |
| Change in marijuana use as measured by self-reported use for each day on the Timeline Followback calendar. | Marijuana use is defined as any day with any marijuana use in the previous 90 days on the Timeline Followback calendar at 3-, 6-, and 9-months post-intake. Marijuana use will be a dichotomous outcome (yes or no). In addition, marijuana use will be validated using a biological test to assess Tetrahydrocannabinol (THC) levels. | 3, 6, and 9 months |
|
prenatal alcohol exposure, marijuana, smoking cessation, computer-delivered intervention, contraception, behavioral intervention, motivational interviewing
|
Marijuana Abuse, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Computer tablet-delivered C4H<br>Two session CHOICES4Health intervention delivered by a computer tablet to address no use or ineffective use of contraception, and risky alcohol use, or cigarette smoking, or marijuana use. | Behavioral: Computer tablet-delivered C4H<br>* Two session CHOICES intervention targeting ineffective contraception and risky alcohol use and/or cigarette smoking and/or marijuana use to reduce the risk of a substance-exposed pregnancy delivered on a computer-tablet.<br>* Other names: C4H-T;|
| Experimental: Person-delivered C4H<br>Two session CHOICES4Health intervention delivered by a counselor to address no use or ineffective use of contraception, and risky alcohol use, or cigarette smoking, or marijuana use. | Behavioral: Person-delivered C4H<br>* Two session CHOICES intervention targeting ineffective contraception and risky alcohol use and/or cigarette smoking and/or marijuana use to reduce the risk of a substance-exposed pregnancy delivered by a counselor.<br>* Other names: C4H-C;|
| Active Comparator: Brief Advice<br>Women will receive advice and educational material from a research assistant about risk drinking, smoking, marijuana, and contraception, depending on their specific risk behaviors, as well as information about women's health. In addition, the women will receive referrals to the Harris Health System's SBIRT clinic if needed. | Behavioral: Brief Advice<br>* Brief advice delivered by a research associate about healthy behaviors for women including use of contraception and alcohol, tobacco, and marijuana use<br>* Other names: BA;|
|
Choices4Health: Intervention to Prevent Substance-exposed Pregnancy
Study Overview
=================
Brief Summary
-----------------
This is a 4-year randomized, controlled study to test the efficacy of the CHOICES4Health-T (C4H-T) delivered by a computerized tablet, CHOICES4Health-C (C4H-C), delivered by a counselor, and brief advice (BA), on reducing preconception substance-exposed pregnancy risk (i.e. drinking below risk levels; tobacco and marijuana cessation; effective contraception use) among women (aged 18-44) presenting to the 13 primary care clinics that serve adults within the Harris Health System. Given the natural fit between contraceptive and HIV prevention counseling the CHOICES4Health interventions will also target HIV sexual risk behaviors.
Detailed Description
-----------------
A randomized group design (N = 240) will be used to test the efficacy of the C4H-C and C4H-T interventions relative to Brief Advice (BA) to reduce the risk of substance-exposed pregnancy) SEP in preconception women of childbearing age. Follow-up assessments will be conducted at 3, 6, and 9 months. Each of the substances targeted in this study (risk drinking, cigarette smoking, and marijuana use) is commonly used relative to other substances and is singly or jointly associated with risk for poor fetal outcomes. Thus, women who are not using effective contraception (i.e., use of effective birth-control methods during all vaginal intercourse) and have any one or more substance-risk behaviors in the 30 days before intake will be eligible for the study. Urn randomization will be used to stratify women on all three substance-risk behaviors to ensure a balanced number of women presenting with alcohol-exposed pregnancy (AEP), tobacco-exposed pregnancy (TEP), and marijuana-exposed pregnancy (MEP) risks across the three study conditions. To address risk distribution for women who present with more than one risk behavior the urn randomization will also be programmed to balance single risk and multiple risk women across the study conditions. In sum, the urn randomization will include four assignment criteria: AEP, TEP, MEP, and multiple risks. Finally, different numbers of women will be needed for each type of substance-exposed pregnancy risk in order to provide sufficient power for the investigator's analytic tests. For example, approximately 25% more women at risk of AEP are required than for TEP to attain the same power. The investigators will include over sampling rules and stopping rules to ensure adequate recruitment for AEP, TEP, and MEP.
Official Title
-----------------
Tablet-based Intervention to Prevent Substance-exposed Pregnancy in Primary Care
Conditions
-----------------
Prenatal Alcohol Exposure, Prenatal Tobacco Exposure, Prenatal Marijuana Exposure
Intervention / Treatment
-----------------
* Behavioral: Computer tablet-delivered C4H
* Behavioral: Person-delivered C4H
* Behavioral: Brief Advice
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women who: are 18-44 years old; have no condition causing infertility (e.g., tubal ligation, hysterectomy, menopause); are not pregnant or planning to become pregnant in the next 12 months; are available for the follow-up period; had vaginal intercourse during the previous 30 days with a fertile man and did not use effective contraception every time AND are drinking at risk levels (more than 3 drinks/day or more than 7 drinks/week); OR are reporting marijuana use in the previous month, OR are currently smoking cigarettes (at least weekly use) during the 30-day baseline period. Exclusion Criteria: Women who: have severe cognitive, and/or psychiatric impairment that precludes cooperation with study protocol, per judgment of the C4H interventionist or research staff; are unable to read, write, and speak English or Spanish; are unable or unwilling to meet study requirements, including followup assessments.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 44 Years
Sexes Eligible for Study
-----------------
Female
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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Computer tablet-delivered C4H<br>Two session CHOICES4Health intervention delivered by a computer tablet to address no use or ineffective use of contraception, and risky alcohol use, or cigarette smoking, or marijuana use. | Behavioral: Computer tablet-delivered C4H<br>* Two session CHOICES intervention targeting ineffective contraception and risky alcohol use and/or cigarette smoking and/or marijuana use to reduce the risk of a substance-exposed pregnancy delivered on a computer-tablet.<br>* Other names: C4H-T;|
| Experimental: Person-delivered C4H<br>Two session CHOICES4Health intervention delivered by a counselor to address no use or ineffective use of contraception, and risky alcohol use, or cigarette smoking, or marijuana use. | Behavioral: Person-delivered C4H<br>* Two session CHOICES intervention targeting ineffective contraception and risky alcohol use and/or cigarette smoking and/or marijuana use to reduce the risk of a substance-exposed pregnancy delivered by a counselor.<br>* Other names: C4H-C;|
| Active Comparator: Brief Advice<br>Women will receive advice and educational material from a research assistant about risk drinking, smoking, marijuana, and contraception, depending on their specific risk behaviors, as well as information about women's health. In addition, the women will receive referrals to the Harris Health System's SBIRT clinic if needed. | Behavioral: Brief Advice<br>* Brief advice delivered by a research associate about healthy behaviors for women including use of contraception and alcohol, tobacco, and marijuana use<br>* Other names: BA;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in risk of alcohol-exposed pregnancy (AEP) as measured by self-reported daily standard drinks, vaginal sex, and use of contraception on the Timeline Followback calendar. | Risk of AEP is defined as any risk drinking (>3 drinks/day or >7 drinks/week on average) and any occurrence of vaginal sex with no use or ineffective use of contraception in the assessment period. Self-reported daily alcohol use (in standard drinks), vaginal intercourse, and contraception (effective use) data from the Timeline Followback will be used to calculate risk of AEP for the previous 90 days. Change in Risk of AEP will be examined at 3-, 6-, and 9-months post-intake. A participant will be considered at risk of AEP at each of the 3-, 6-, and 9 month timepoints if the participant had any occurrence of vaginal sex without the use of effective contraception and had more than 3 standard drinks on any day or more than 7 standard drinks per week on average in any 30 day period in the previous 90 days. Risk of AEP will be a dichotomous outcome (at risk of AEP or at reduced risk of AEP). | 3, 6, and 9 months |
| Change in risk of tobacco-exposed pregnancy (TEP) as measured by self-reported daily number of cigarettes, vaginal sex, and use of contraception on the Timeline Followback calendar. | Risk of TEP is defined as currently smoking cigarettes (at least weekly use) and any occurrence of vaginal sex with no use or ineffective use of contraception in the assessment period. Self-reported data from the Timeline Followback will be used to calculate risk of TEP for the previous 90 days at 3-, 6 , and 9 months post-intake. A participant will be considered at risk of TEP at each of the 3-, 6-, and 9 month timepoints if the participant had any occurrence of vaginal sex without the use of effective contraception and she had at least weekly smoking in any 30 day period in the previous 90 days. Risk of TEP will be a dichotomous outcome (at risk of TEP or at reduced risk of TEP). | 3, 6, and 9 months |
| Change in risk of marijuana-exposed pregnancy (MEP) as measured by self-reported marijuana use, vaginal sex, and use of contraception on the Timeline Followback calendar. | Risk of MEP is defined as any day with marijuana use and any occurrence of vaginal sex with no use or ineffective use of contraception in the assessment period. Self-reported data from the Timeline Followback will be used to calculate risk of MEP for the previous 90 days at 3-, 6- , and 9 months post-intake. A participant will be considered at risk of MEP at each of the 3-, 6-, and 9 month timepoints if the participant had any occurrence of vaginal sex without the use of effective contraception and had any day with marijuana use in any 30 day period in the previous 90 days. Risk of MEP will be a dichotomous outcome (at risk of MEP or at reduced risk of MEP). | 3, 6, and 9 months |
| Change in risk drinking as measured by self-reported number of standard drinks on the Timeline Followback calendar. | Risk drinking is defined as drinking more than 3 standard drinks on any day or drinking more than 7 standard drinks in a week on average in the previous 90 days. Self-reported data from the Timeline Followback will be used to calculate risk drinking for the previous 90 days at 3-, 6-, and 9-months post-intake. Risk drinking will be a dichotomous outcome (yes or no). | 3, 6, and 9 months |
| Change in cigarette smoking as measured by self-reported number of cigarettes smoked each day on the Timeline Followback calendar. | Cigarette smoking is defined as at least weekly cigarette smoking in the previous 90 days on the Timeline Followback calendar at 3-, 6-, and 9-months post-intake. Cigarette smoking will be a dichotomous outcome (yes or no). In addition, smoking will be validated using biological test to assess cotinine levels. | 3, 6, and 9 months |
| Change in marijuana use as measured by self-reported use for each day on the Timeline Followback calendar. | Marijuana use is defined as any day with any marijuana use in the previous 90 days on the Timeline Followback calendar at 3-, 6-, and 9-months post-intake. Marijuana use will be a dichotomous outcome (yes or no). In addition, marijuana use will be validated using a biological test to assess Tetrahydrocannabinol (THC) levels. | 3, 6, and 9 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
prenatal alcohol exposure, marijuana, smoking cessation, computer-delivered intervention, contraception, behavioral intervention, motivational interviewing
|
|
NCT03445689
|
Oxygenation Instability and Maturation of Control of Breathing in Premature Infants
|
Premature infants present with significant oxygenation instability in the form of frequent spontaneous episodes of hypoxemia during the first weeks after birth. These infants are also exposed to hyperoxemia.~The objective of this study is to determine the extent to which exposure to frequent episodes of hypoxemia and hyperoxemia in extreme premature infants during the early stages of their evolving lung disease is associated with altered maturation and function of their respiratory control system.~This study is part of the Prematurity-Related Ventilatory Control (Pre-Vent): Role in Respiratory Outcomes Clinical Research Centers (CRC) (U01) cooperative program of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).
|
Most extreme premature infants present with respiratory failure due to altered lung function compounded by breathing instability due to an immature respiratory control function.~Premature infants present with significant oxygenation instability in the form of frequent spontaneous episodes of hypoxemia during the first weeks after birth. As a result, these infants receive oxygen supplementation but this is often excessive and these infants are also exposed to hyperoxemia. The extent to which these episodes of hypoxemia or the exposure to hyperoxemia impact on the maturation and function of the control of breathing system in extreme premature infants during the evolving stages of their respiratory disease is unknown. This is a prospective study that will systematically evaluate such association in extreme premature infants.~The main objective of this study is to determine the extent to which exposure to frequent episodes of hypoxemia and hyperoxemia in extreme premature infants during the early stages of their evolving lung disease is associated with altered maturation and function of their respiratory control system.~This study is part of the Prematurity-Related Ventilatory Control (Pre-Vent): Role in Respiratory Outcomes Clinical Research Centers (CRC) (U01) cooperative program of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).
|
Oxygenation Instability and Maturation of Control of Breathing in Premature Infants
|
Infant,Premature
|
* Other: Assessment of oxygenation instability
* Other: Determination of mechanisms of hypoxemia episodes
* Other: Assessment of respiratory instability
* Other: apneic threshold of CO2
* Other: Assessment of peripheral chemoreceptor function
* Other: Assessment of central chemo-receptor function
|
Inclusion Criteria:~Premature infants born at 23 0/7- 28 6/7 weeks gestational age~Postnatal age up to equivalent to 36 weeks postmenstrual age~Requiring supplemental oxygen and/or receiving mechanical ventilation, CPAP, nasal ventilation or nasal cannula~Exclusion Criteria:~Severe congenital anomalies that may affect life expectancy or pulmonary or neurosensory development~Severe CNS pathology that may alter respiratory control function
| null | null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral chemoreceptor control of breathing function | Ventilatory response to oxygen (Dejours test) | at 32 weeks corrected postmenstrual age |
| Peripheral chemoreceptor control of breathing function | Ventilatory response to oxygen (Dejours test) | at 36 weeks corrected postmenstrual age |
| Central chemoreceptor control of breathing function | Ventilatory response to carbon dioxide | at 32 weeks corrected postmenstrual age |
| Central chemoreceptor control of breathing function | Ventilatory response to carbon dioxide | at 36 weeks corrected postmenstrual age |
| Change in peripheral chemoreceptor control of breathing function | Ventilatory response to oxygen (Dejours test) | Change from 32 to 36 weeks postmenstrual age |
| Change in central chemoreceptor control of breathing function | Ventilatory response to carbon dioxide | Change from 32 to 36 weeks postmenstrual age |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilatory stability - Apnea frequency | Frequency of apnea episodes per hour | at 32 and 36 weeks corrected postmenstrual age |
| Ventilatory stability - Periodic breathing density | Percent of time with periodic breathing | at 32 and 36 weeks corrected postmenstrual age |
| Ventilatory stability - Time series analysis of inter-breath interval | Tail slope of the log-scaled probability density function of the inter-breath time series | at 32 and 36 weeks corrected postmenstrual age |
| Mechanisms of episodic hypoxemia | Classify etiology of episodes of hypoxemia as central, obstructive, or mixed apnea or active exhalation based on measurements of respiratory inductance plethysmography, esophageal pressure | at 32 and 36 weeks corrected postmenstrual age |
| Apneic CO2 threshold in central apnea | Carbon dioxide level change at onset of central apnea | at 32 and 36 weeks corrected postmenstrual age |
| Apneic CO2 threshold during mechanical ventilation | Carbon dioxide level change at onset of central apnea with stepwise increase in ventilator rate | at 32 and 36 weeks corrected postmenstrual age |
|
Premature Birth, Obstetric Labor, Premature, Obstetric Labor Complications, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases
|
| Intervention/Treatment |
| --- |
|Other: Assessment of oxygenation instability|Recordings of SpO2 and heart rate will be analyzed by dedicated software to obtain frequency, duration and severity of episodes of hypoxemia and hyperoxemia.|
|Other: Determination of mechanisms of hypoxemia episodes|Recordings of SpO2, heart rate, esophageal pressure, tidal volume, minute volume, respiratory rate and transcutaneous PCO2 will be analyzed to determine the prevalence, severity and duration of hypoxemia episodes produced by the different mechanisms.|
|Other: Assessment of respiratory instability|Recordings of tidal volume, minute volume and respiratory rate will be analyzed to determine frequency of apnea, periodic breathing, distribution of inter-breath intervals.|
|Other: apneic threshold of CO2|In mechanically ventilated infants the apneic threshold of CO2 will be measured by transcutaneous PCO2 following a step wise increase in ventilator rate until spontaneous breathing ceases transiently. In spontaneously breathing infants the apnea threshold of CO2 will be measured during episodes central apnea.|
|Other: Assessment of peripheral chemoreceptor function|The Dejours test will be used to assess peripheral chemoreceptor function by measuring the immediate ventilatory response to high-inspired oxygen.|
|Other: Assessment of central chemo-receptor function|Central chemo-receptor function will be assessed by measuring the ventilatory response to inspired CO2.|
|
Oxygenation Instability and Maturation of Control of Breathing in Premature Infants
Study Overview
=================
Brief Summary
-----------------
Premature infants present with significant oxygenation instability in the form of frequent spontaneous episodes of hypoxemia during the first weeks after birth. These infants are also exposed to hyperoxemia. The objective of this study is to determine the extent to which exposure to frequent episodes of hypoxemia and hyperoxemia in extreme premature infants during the early stages of their evolving lung disease is associated with altered maturation and function of their respiratory control system. This study is part of the Prematurity-Related Ventilatory Control (Pre-Vent): Role in Respiratory Outcomes Clinical Research Centers (CRC) (U01) cooperative program of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).
Detailed Description
-----------------
Most extreme premature infants present with respiratory failure due to altered lung function compounded by breathing instability due to an immature respiratory control function. Premature infants present with significant oxygenation instability in the form of frequent spontaneous episodes of hypoxemia during the first weeks after birth. As a result, these infants receive oxygen supplementation but this is often excessive and these infants are also exposed to hyperoxemia. The extent to which these episodes of hypoxemia or the exposure to hyperoxemia impact on the maturation and function of the control of breathing system in extreme premature infants during the evolving stages of their respiratory disease is unknown. This is a prospective study that will systematically evaluate such association in extreme premature infants. The main objective of this study is to determine the extent to which exposure to frequent episodes of hypoxemia and hyperoxemia in extreme premature infants during the early stages of their evolving lung disease is associated with altered maturation and function of their respiratory control system. This study is part of the Prematurity-Related Ventilatory Control (Pre-Vent): Role in Respiratory Outcomes Clinical Research Centers (CRC) (U01) cooperative program of the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH).
Official Title
-----------------
Oxygenation Instability and Maturation of Control of Breathing in Premature Infants
Conditions
-----------------
Infant,Premature
Intervention / Treatment
-----------------
* Other: Assessment of oxygenation instability
* Other: Determination of mechanisms of hypoxemia episodes
* Other: Assessment of respiratory instability
* Other: apneic threshold of CO2
* Other: Assessment of peripheral chemoreceptor function
* Other: Assessment of central chemo-receptor function
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Premature infants born at 23 0/7- 28 6/7 weeks gestational age Postnatal age up to equivalent to 36 weeks postmenstrual age Requiring supplemental oxygen and/or receiving mechanical ventilation, CPAP, nasal ventilation or nasal cannula Exclusion Criteria: Severe congenital anomalies that may affect life expectancy or pulmonary or neurosensory development Severe CNS pathology that may alter respiratory control function
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Intervention/Treatment |
| --- |
|Other: Assessment of oxygenation instability|Recordings of SpO2 and heart rate will be analyzed by dedicated software to obtain frequency, duration and severity of episodes of hypoxemia and hyperoxemia.|
|Other: Determination of mechanisms of hypoxemia episodes|Recordings of SpO2, heart rate, esophageal pressure, tidal volume, minute volume, respiratory rate and transcutaneous PCO2 will be analyzed to determine the prevalence, severity and duration of hypoxemia episodes produced by the different mechanisms.|
|Other: Assessment of respiratory instability|Recordings of tidal volume, minute volume and respiratory rate will be analyzed to determine frequency of apnea, periodic breathing, distribution of inter-breath intervals.|
|Other: apneic threshold of CO2|In mechanically ventilated infants the apneic threshold of CO2 will be measured by transcutaneous PCO2 following a step wise increase in ventilator rate until spontaneous breathing ceases transiently. In spontaneously breathing infants the apnea threshold of CO2 will be measured during episodes central apnea.|
|Other: Assessment of peripheral chemoreceptor function|The Dejours test will be used to assess peripheral chemoreceptor function by measuring the immediate ventilatory response to high-inspired oxygen.|
|Other: Assessment of central chemo-receptor function|Central chemo-receptor function will be assessed by measuring the ventilatory response to inspired CO2.|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral chemoreceptor control of breathing function | Ventilatory response to oxygen (Dejours test) | at 32 weeks corrected postmenstrual age |
| Peripheral chemoreceptor control of breathing function | Ventilatory response to oxygen (Dejours test) | at 36 weeks corrected postmenstrual age |
| Central chemoreceptor control of breathing function | Ventilatory response to carbon dioxide | at 32 weeks corrected postmenstrual age |
| Central chemoreceptor control of breathing function | Ventilatory response to carbon dioxide | at 36 weeks corrected postmenstrual age |
| Change in peripheral chemoreceptor control of breathing function | Ventilatory response to oxygen (Dejours test) | Change from 32 to 36 weeks postmenstrual age |
| Change in central chemoreceptor control of breathing function | Ventilatory response to carbon dioxide | Change from 32 to 36 weeks postmenstrual age |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilatory stability - Apnea frequency | Frequency of apnea episodes per hour | at 32 and 36 weeks corrected postmenstrual age |
| Ventilatory stability - Periodic breathing density | Percent of time with periodic breathing | at 32 and 36 weeks corrected postmenstrual age |
| Ventilatory stability - Time series analysis of inter-breath interval | Tail slope of the log-scaled probability density function of the inter-breath time series | at 32 and 36 weeks corrected postmenstrual age |
| Mechanisms of episodic hypoxemia | Classify etiology of episodes of hypoxemia as central, obstructive, or mixed apnea or active exhalation based on measurements of respiratory inductance plethysmography, esophageal pressure | at 32 and 36 weeks corrected postmenstrual age |
| Apneic CO2 threshold in central apnea | Carbon dioxide level change at onset of central apnea | at 32 and 36 weeks corrected postmenstrual age |
| Apneic CO2 threshold during mechanical ventilation | Carbon dioxide level change at onset of central apnea with stepwise increase in ventilator rate | at 32 and 36 weeks corrected postmenstrual age |
|
||
NCT00610584
|
Acupuncture for Seasonal Allergic Rhinitis
|
Acupuncture is widely use by patients with seasonal allergic rhinitis (SAR), although there is only limited evidence of its effectiveness. The aim of this three armed randomised controlled multicentre trial is to investigate the efficacy of acupuncture plus rescue medication vs. minimal (sham) acupuncture plus rescue medication vs. (b) rescue medication alone in the treatment of seasonal allergic rhinitis.
|
Acupuncture is widely use by patients with seasonal allergic rhinitis (SAR), although there is only limited evidence of its effectiveness. The aims of this 3-armed, randomised controlled trial are to investigate whether acupuncture plus rescue medication is non-inferior (closed testing procedure: in case of success in non-inferiority: test of superiority) to minimal acupuncture plus rescue medication in the treatment of SAR (closed testing procedure: closed testing procedure: in case of success in non-inferiority: test of superiority), and whether acupuncture plus rescue medication is non-inferior to rescue medication alone consisting only of oral antihistamines for this indication. The trial interventions will be performed in approximately 40 outpatient centres in Germany. In total, 400 patients with SAR will be randomised to one of three groups: acupuncture plus rescue medication, minimal acupuncture (i.e. superficial needling at non-acupuncture points) plus rescue medication, or rescue medication only. Rescue medication will consist of oral antihistamines. Acupuncture and minimal acupuncture will be administered by physicians specialised in acupuncture and will consist of 12 sessions per patient in the first 8 weeks. Patients in the rescue medication group will receive 12 sessions of acupuncture after 8 weeks. The primary outcome measures will be the mean of Rhinitis Quality of Life Questionnaire score (RQLQ scores between weeks 6 and 8 of the first year (adjusted for baseline values) and the Rescue Medication Score (RMS) between weeks 6 and 8 of the first year (adjusted for baseline values).
|
Acupuncture for Seasonal Allergic Rhinitis (ACUSAR) - A Randomised Controlled Trial
|
Seasonal Allergic Rhinitis
|
* Procedure: acupuncture
* Procedure: minimal (sham)acupuncture
* Drug: cetirizine dihydrochloride (rescue medication)
|
Inclusion Criteria:~Female or male patients (aged 16-45 years) with seasonal allergic rhinitis, clinically positive and test positive (skin-prick test and/or RAST) to grass and birch pollen~Patients with >2 years of moderate to severe SAR~Positive skin-prick test and/or RAST (at least class 2) results~Visual analogue scale >40mm and <80 mm for SAR symptoms during the past year~Patients must be able to complete a diary for self-evaluation of symptoms and recording use of anti-symptomatic medication~Use of, or indication for, oral antihistamines as anti-allergic medication~Written informed consent~Exclusion Criteria:~Perennial SAR or other types of chronic rhinitis~Allergic asthma and/or moderate to severe atopic dermatitis~Active tuberculosis~Autoimmune disorders~Severe chronic inflammatory diseases~History of anaphylactic reactions~Hypersensitivity to Rescue medication or related drugs used in study related drugs~Specific immunotherapy >3 years~Simultaneous participation in other clinical trials~Serious acute or chronic organic disease or mental disorder~Pregnancy or breast feeding~Allergy desensitisation therapy (current, during the past two years, or planned in the next two years)~Blood coagulation disorder and/or current use of anticoagulants~Previous acupuncture treatment for SAR~Any Complementary and alternative medicine treatment at the moment, in the last three months or planned in the next two years
|
16 Years
|
45 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rhinitis Quality of Life Questionnaire score (RQLQ scores between weeks 6 and 8 of the first year (adjusted for baseline values) and the Rescue Medication Score between weeks 6 and 8 of the first year (adjusted for baseline values). | | Weeks 6 and 8 of the first year (adjusted for baseline values). |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life (SF-36), responder rate (RQLQ score of 0.5 or more), global evaluation of treatment success, VAS (0-100 mm) overall symptom severity and nasal, eye, pharyngeal and common symptoms, safety, patients constitution, health economic analyses. | | Baseline, 8 weeks and 16 weeks in the first year and baseline and week 8 in the second year |
|
seasonal allergic rhinitis, acupuncture, RCT, CAM
|
Physiological Effects of Drugs, Cetirizine, Anti-Allergic Agents, Histamine H1 Antagonists, Non-Sedating, Histamine H1 Antagonists, Histamine Antagonists, Histamine Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>verum acupuncture plus rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily)) | Procedure: acupuncture<br>* arm 1: verum acupuncture group: 12 interventions (semi-standardised): 8 in the first 4 weeks and 4 in the next 4 weeks + rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily))<br>|
| Placebo Comparator: 2<br>minimal (sham) acupuncture plus rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily)) | Procedure: minimal (sham)acupuncture<br>* arm 2: minimal (sham) acupuncture group: 12 interventions (standardised): 8 in the first 4 weeks and 4 in the next 4 weeks + rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily))<br>|
| Active Comparator: 3<br>rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily))alone | Drug: cetirizine dihydrochloride (rescue medication)<br>* arm 3: rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily)) alone<br>|
|
Acupuncture for Seasonal Allergic Rhinitis
Study Overview
=================
Brief Summary
-----------------
Acupuncture is widely use by patients with seasonal allergic rhinitis (SAR), although there is only limited evidence of its effectiveness. The aim of this three armed randomised controlled multicentre trial is to investigate the efficacy of acupuncture plus rescue medication vs. minimal (sham) acupuncture plus rescue medication vs. (b) rescue medication alone in the treatment of seasonal allergic rhinitis.
Detailed Description
-----------------
Acupuncture is widely use by patients with seasonal allergic rhinitis (SAR), although there is only limited evidence of its effectiveness. The aims of this 3-armed, randomised controlled trial are to investigate whether acupuncture plus rescue medication is non-inferior (closed testing procedure: in case of success in non-inferiority: test of superiority) to minimal acupuncture plus rescue medication in the treatment of SAR (closed testing procedure: closed testing procedure: in case of success in non-inferiority: test of superiority), and whether acupuncture plus rescue medication is non-inferior to rescue medication alone consisting only of oral antihistamines for this indication. The trial interventions will be performed in approximately 40 outpatient centres in Germany. In total, 400 patients with SAR will be randomised to one of three groups: acupuncture plus rescue medication, minimal acupuncture (i.e. superficial needling at non-acupuncture points) plus rescue medication, or rescue medication only. Rescue medication will consist of oral antihistamines. Acupuncture and minimal acupuncture will be administered by physicians specialised in acupuncture and will consist of 12 sessions per patient in the first 8 weeks. Patients in the rescue medication group will receive 12 sessions of acupuncture after 8 weeks. The primary outcome measures will be the mean of Rhinitis Quality of Life Questionnaire score (RQLQ scores between weeks 6 and 8 of the first year (adjusted for baseline values) and the Rescue Medication Score (RMS) between weeks 6 and 8 of the first year (adjusted for baseline values).
Official Title
-----------------
Acupuncture for Seasonal Allergic Rhinitis (ACUSAR) - A Randomised Controlled Trial
Conditions
-----------------
Seasonal Allergic Rhinitis
Intervention / Treatment
-----------------
* Procedure: acupuncture
* Procedure: minimal (sham)acupuncture
* Drug: cetirizine dihydrochloride (rescue medication)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female or male patients (aged 16-45 years) with seasonal allergic rhinitis, clinically positive and test positive (skin-prick test and/or RAST) to grass and birch pollen Patients with >2 years of moderate to severe SAR Positive skin-prick test and/or RAST (at least class 2) results Visual analogue scale >40mm and <80 mm for SAR symptoms during the past year Patients must be able to complete a diary for self-evaluation of symptoms and recording use of anti-symptomatic medication Use of, or indication for, oral antihistamines as anti-allergic medication Written informed consent Exclusion Criteria: Perennial SAR or other types of chronic rhinitis Allergic asthma and/or moderate to severe atopic dermatitis Active tuberculosis Autoimmune disorders Severe chronic inflammatory diseases History of anaphylactic reactions Hypersensitivity to Rescue medication or related drugs used in study related drugs Specific immunotherapy >3 years Simultaneous participation in other clinical trials Serious acute or chronic organic disease or mental disorder Pregnancy or breast feeding Allergy desensitisation therapy (current, during the past two years, or planned in the next two years) Blood coagulation disorder and/or current use of anticoagulants Previous acupuncture treatment for SAR Any Complementary and alternative medicine treatment at the moment, in the last three months or planned in the next two years
Ages Eligible for Study
-----------------
Minimum Age: 16 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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>verum acupuncture plus rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily)) | Procedure: acupuncture<br>* arm 1: verum acupuncture group: 12 interventions (semi-standardised): 8 in the first 4 weeks and 4 in the next 4 weeks + rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily))<br>|
| Placebo Comparator: 2<br>minimal (sham) acupuncture plus rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily)) | Procedure: minimal (sham)acupuncture<br>* arm 2: minimal (sham) acupuncture group: 12 interventions (standardised): 8 in the first 4 weeks and 4 in the next 4 weeks + rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily))<br>|
| Active Comparator: 3<br>rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily))alone | Drug: cetirizine dihydrochloride (rescue medication)<br>* arm 3: rescue medication (up to 2 doses of second-generation oral antihistamines daily (e.g. 2 x 1 cetirizine dihydrochloride/daily)) alone<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rhinitis Quality of Life Questionnaire score (RQLQ scores between weeks 6 and 8 of the first year (adjusted for baseline values) and the Rescue Medication Score between weeks 6 and 8 of the first year (adjusted for baseline values). | | Weeks 6 and 8 of the first year (adjusted for baseline values). |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life (SF-36), responder rate (RQLQ score of 0.5 or more), global evaluation of treatment success, VAS (0-100 mm) overall symptom severity and nasal, eye, pharyngeal and common symptoms, safety, patients constitution, health economic analyses. | | Baseline, 8 weeks and 16 weeks in the first year and baseline and week 8 in the second year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
seasonal allergic rhinitis, acupuncture, RCT, CAM
|
NCT02197455
|
Tofacitnib for the Treatment of Alopecia Areata and Variants
|
The purpose of this study is to investigate the ability of tofacitinib citrate, a Janus kinase inhibitor, to generate hair regrowth in patients with moderate to severe alopecia areata and its variants.
|
This study is an open-label pilot study. Participants will be treated with oral tofacitinib for a maximum of 5 months. Participants will be evaluated at 3 months after completion of therapy to evaluate for durability of response, late response and/or late adverse effects.
|
Tofacitnib for the Treatment of Alopecia Areata and Variants
|
Alopecia Areata (AA), Alopecia Totalis (AT), Alopecia Universalis (AU)
|
* Drug: Tofacitinib Administration
|
Inclusion Criteria:~Age >= 18 years old~Diagnosis of alopecia areata with >50% scalp involvement, alopecia totalis, or alopecia universalis~Hair loss present for at least 6 months~No treatment for alopecia areata in past 2 months~No evidence of hair regrowth~Females of childbearing potential must use birth control while taking the medication and there must be a negative pregnancy test documented prior to starting the medication~Exclusion Criteria:~Age <18 years old~Patients have received treatment known to affect alopecia areata within 2 months of enrolling in the study~Patients with a history of malignancy (except history of successfully treated basal cell or squamous cell carcinoma of the skin)~Patients known to be HIV or hepatitis B or C positive~Patients with positive tuberculin skin test or positive QuantiFERON TB test~Patients with leukopenia or anemia~Patients with renal or hepatic impairment~Patients with peptic ulcer disease~Patients taking immunosuppressive medications, including but not limited to prednisone, methotrexate, mycophenolate mofetil, azathioprine, tacrolimus, cyclosporine, or TNH-alpha inhibitors~Women of childbearing potential who are unable or unwilling to use birth control while taking the medication~Women who are pregnant or nursing
|
18 Years
|
90 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Severity of Alopecia Tool (SALT) Score | SALT score range is from 0 (no hair loss) to 100 (100% hair loss) | 3 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Skindex 16 Scores | Skindex 16 is a quality of life questionaire with a range of 0-100 wherein 1 is not bothered by the condition and 100 is always bothered by the condition | 3 months |
|
Tofacitinib, Janus Kinase Inhibitors, Protein Kinase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tofacitinib Administration<br>5 mg of Tofacitinib will be taken by mouth twice daily for 3 months. | Drug: Tofacitinib Administration<br>* 5 mg of Tofacitinib will be taken by mouth twice daily for 3 months.<br>|
|
Tofacitnib for the Treatment of Alopecia Areata and Variants
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the ability of tofacitinib citrate, a Janus kinase inhibitor, to generate hair regrowth in patients with moderate to severe alopecia areata and its variants.
Detailed Description
-----------------
This study is an open-label pilot study. Participants will be treated with oral tofacitinib for a maximum of 5 months. Participants will be evaluated at 3 months after completion of therapy to evaluate for durability of response, late response and/or late adverse effects.
Official Title
-----------------
Tofacitnib for the Treatment of Alopecia Areata and Variants
Conditions
-----------------
Alopecia Areata (AA), Alopecia Totalis (AT), Alopecia Universalis (AU)
Intervention / Treatment
-----------------
* Drug: Tofacitinib Administration
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >= 18 years old Diagnosis of alopecia areata with >50% scalp involvement, alopecia totalis, or alopecia universalis Hair loss present for at least 6 months No treatment for alopecia areata in past 2 months No evidence of hair regrowth Females of childbearing potential must use birth control while taking the medication and there must be a negative pregnancy test documented prior to starting the medication Exclusion Criteria: Age <18 years old Patients have received treatment known to affect alopecia areata within 2 months of enrolling in the study Patients with a history of malignancy (except history of successfully treated basal cell or squamous cell carcinoma of the skin) Patients known to be HIV or hepatitis B or C positive Patients with positive tuberculin skin test or positive QuantiFERON TB test Patients with leukopenia or anemia Patients with renal or hepatic impairment Patients with peptic ulcer disease Patients taking immunosuppressive medications, including but not limited to prednisone, methotrexate, mycophenolate mofetil, azathioprine, tacrolimus, cyclosporine, or TNH-alpha inhibitors Women of childbearing potential who are unable or unwilling to use birth control while taking the medication Women who are pregnant or nursing
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?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tofacitinib Administration<br>5 mg of Tofacitinib will be taken by mouth twice daily for 3 months. | Drug: Tofacitinib Administration<br>* 5 mg of Tofacitinib will be taken by mouth twice daily for 3 months.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Severity of Alopecia Tool (SALT) Score | SALT score range is from 0 (no hair loss) to 100 (100% hair loss) | 3 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Skindex 16 Scores | Skindex 16 is a quality of life questionaire with a range of 0-100 wherein 1 is not bothered by the condition and 100 is always bothered by the condition | 3 months |
|
|
NCT00137852
|
Cisplatin, CPT-11 and Celecoxib With Radiation Therapy and Surgery for Operable Esophageal Cancer
|
This is a study for patients with resectable, locally advanced esophageal cancer. There is evidence to suggest that celecoxib in combination with cisplatin and irinotecan (CPT-11) may work well with radiation therapy to kill cancer cells. The primary goal is to develop a well-tolerated cancer treatment that has an acceptable response rate.
|
Patients will take celecoxib orally twice daily 3 days prior to radiation therapy and until one week prior to surgery. Celecoxib will then be restarted when the patient is discharged from the hospital following surgery and continued for 26 weeks.~Patients will receive chemotherapy (cisplatin and irinotecan) weekly on weeks 1, 2, 4 and 5 during radiation therapy. Chemotherapy must occur on or before the fifth day of radiation therapy.~Radiation therapy will be performed 5 days a week over a 5.6 week period.~Patients will undergo an esophagectomy within 4-8 weeks of chemotherapy/radiation therapy. Technically accessible lymph nodes will also be removed.~During chemotherapy/radiation therapy, a physical exam and bloodwork will be conducted weekly.~Between chemotherapy/radiation therapy and surgery a physical exam, bloodwork and CT of chest, abdomen, and pelvis should be performed.~After the completion of treatment and surgery, a physical exam and bloodwork should be done every 6 weeks for 6 months, then every 3 months for 1 1/2 years, then every 6 months for 3 years.
|
Phase II Trial of Cisplatin, CPT-11, Celecoxib (PCC), Concurrent Radiation Therapy, and Surgery for Resectable Esophageal Cancer
|
Esophageal Cancer
|
* Drug: Cisplatin
* Drug: Irinotecan
* Drug: Celecoxib
* Procedure: Radiation Therapy
* Procedure: Esophagectomy
|
Inclusion Criteria:~Age greater than or equal to 18 years.~Adenocarcinoma or squamous cell carcinoma of the esophagus, including the gastroesophageal junction, histologically confirmed, American Joint Committee on Cancer (AJCC) Stage IIA, IIB, III. Additionally, patients with tumors of the lower thoracic esophagus and gastroesophageal junction may have regional lymph node involvement (M1A-Stage IVA), as long as the lymphadenopathy can be entirely encompassed by the radiation field.~Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.~Neutrophils greater than or equal to 1,500/ μL.~Platelets greater than or equal to 100,000/ μL.~Serum bilirubin less than or equal to 1.5 mg/dl.~Serum creatinine less than or equal to 1.5 mg/dl.~Aspartamine transaminase (AST or SGOT) less than or equal to 3x upper institutional normal limit.~Alkaline phosphatase less than or equal to 5x upper institutional normal limit.~Exclusion Criteria:~No prior surgery for esophageal or gastro-esophageal junction cancer.~No prior chemotherapy or radiation therapy.~Biopsy proven tumor invasion of the tracheobronchial tree or a tracheoesophageal fistula.~Metastatic disease to distant organs (e.g. liver, lungs, bone) or non-regional lymph nodes. Patients with supraclavicular/cervical lymph node involvement or patients with a proximal esophageal primary and celiac/gastro-hepatic lymph node involvement are also excluded.~Patients with co-morbid disease that, in the opinion of the investigator, makes combined chemo-radiotherapy inadvisable (e.g. New York State Grade III-IV heart disease, myocardial infarction in the last 4 months, uncontrolled infection, uncontrolled diabetes, uncontrolled hypertension, uncontrolled psychiatric illness or organ allograft(s) on immunosuppressive therapy).~Pregnant or lactating women or women of childbearing potential with either a positive or no pregnancy test at baseline.~Women of childbearing potential not using a reliable and appropriate contraceptive method. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.)~Other active malignancy (i.e. hematologic malignancy, metastatic solid tumor, or resected Stage I-IV solid tumor less than 3 years after resection).~Patients with known Gilbert's disease or interstitial pulmonary fibrosis.~Patients with prior severe reaction to nonsteroidal anti-inflammatory drugs (NSAIDs), sulfonamides, or celecoxib.~Patients with a history of seizure disorders who are receiving antiepileptic medication.~Positive malignant cytology of the pleura, pericardium or peritoneum.~Uncontrolled diarrhea (National Cancer Institute Common Toxicity Criteria [NCI CTC] greater than or equal to Grade 2).~Peripheral neuropathy (NCI CTC greater than or equal to Grade 2).~Symptomatic hearing loss, requiring a hearing aid or for which a hearing aid has been suggested by a health professional.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of combination of chemotherapy, radiation therapy and surgery in resectable esophageal carcinoma | | |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the side effects of chemotherapy and radiation therapy in patients with resectable esophageal carcinoma | | 2 years |
|
Esophageal Cancer, Resectable Esophageal Cancer, Radiation Therapy, Celecoxib, Irinotecan, Cisplatin
|
Celecoxib, Irinotecan, Antineoplastic Agents, Topoisomerase I Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Anti-Inflammatory Agents, Non-Steroidal, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Anti-Inflammatory Agents, Antirheumatic Agents, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cisplatin/CPT-11/Celecoxib/XRT/Surgery<br>Cisplatin, CPT-11 and Celecoxib With Radiation Therapy and Surgery for Operable Esophageal Cancer | Drug: Cisplatin<br>* Given weekly on weeks 1, 2, 4 and 5 during radiation therapy.<br>Drug: Irinotecan<br>* Given weekly on weeks 1, 2, 4 and 5 during radiation therapy<br>* Other names: CPT-11;Drug: Celecoxib<br>* Given twice daily 3 days prior to radiation and up until one week prior to surgery. It will then be started again once the participant is released from the hospital following surgery for 26 weeks.<br>Procedure: Radiation Therapy<br>* 5 days a week for 5-6 weeks<br>Procedure: Esophagectomy<br>* Within 4-8 weeks of chemoradiation therapy<br>|
|
Cisplatin, CPT-11 and Celecoxib With Radiation Therapy and Surgery for Operable Esophageal Cancer
Study Overview
=================
Brief Summary
-----------------
This is a study for patients with resectable, locally advanced esophageal cancer. There is evidence to suggest that celecoxib in combination with cisplatin and irinotecan (CPT-11) may work well with radiation therapy to kill cancer cells. The primary goal is to develop a well-tolerated cancer treatment that has an acceptable response rate.
Detailed Description
-----------------
Patients will take celecoxib orally twice daily 3 days prior to radiation therapy and until one week prior to surgery. Celecoxib will then be restarted when the patient is discharged from the hospital following surgery and continued for 26 weeks. Patients will receive chemotherapy (cisplatin and irinotecan) weekly on weeks 1, 2, 4 and 5 during radiation therapy. Chemotherapy must occur on or before the fifth day of radiation therapy. Radiation therapy will be performed 5 days a week over a 5.6 week period. Patients will undergo an esophagectomy within 4-8 weeks of chemotherapy/radiation therapy. Technically accessible lymph nodes will also be removed. During chemotherapy/radiation therapy, a physical exam and bloodwork will be conducted weekly. Between chemotherapy/radiation therapy and surgery a physical exam, bloodwork and CT of chest, abdomen, and pelvis should be performed. After the completion of treatment and surgery, a physical exam and bloodwork should be done every 6 weeks for 6 months, then every 3 months for 1 1/2 years, then every 6 months for 3 years.
Official Title
-----------------
Phase II Trial of Cisplatin, CPT-11, Celecoxib (PCC), Concurrent Radiation Therapy, and Surgery for Resectable Esophageal Cancer
Conditions
-----------------
Esophageal Cancer
Intervention / Treatment
-----------------
* Drug: Cisplatin
* Drug: Irinotecan
* Drug: Celecoxib
* Procedure: Radiation Therapy
* Procedure: Esophagectomy
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age greater than or equal to 18 years. Adenocarcinoma or squamous cell carcinoma of the esophagus, including the gastroesophageal junction, histologically confirmed, American Joint Committee on Cancer (AJCC) Stage IIA, IIB, III. Additionally, patients with tumors of the lower thoracic esophagus and gastroesophageal junction may have regional lymph node involvement (M1A-Stage IVA), as long as the lymphadenopathy can be entirely encompassed by the radiation field. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Neutrophils greater than or equal to 1,500/ μL. Platelets greater than or equal to 100,000/ μL. Serum bilirubin less than or equal to 1.5 mg/dl. Serum creatinine less than or equal to 1.5 mg/dl. Aspartamine transaminase (AST or SGOT) less than or equal to 3x upper institutional normal limit. Alkaline phosphatase less than or equal to 5x upper institutional normal limit. Exclusion Criteria: No prior surgery for esophageal or gastro-esophageal junction cancer. No prior chemotherapy or radiation therapy. Biopsy proven tumor invasion of the tracheobronchial tree or a tracheoesophageal fistula. Metastatic disease to distant organs (e.g. liver, lungs, bone) or non-regional lymph nodes. Patients with supraclavicular/cervical lymph node involvement or patients with a proximal esophageal primary and celiac/gastro-hepatic lymph node involvement are also excluded. Patients with co-morbid disease that, in the opinion of the investigator, makes combined chemo-radiotherapy inadvisable (e.g. New York State Grade III-IV heart disease, myocardial infarction in the last 4 months, uncontrolled infection, uncontrolled diabetes, uncontrolled hypertension, uncontrolled psychiatric illness or organ allograft(s) on immunosuppressive therapy). Pregnant or lactating women or women of childbearing potential with either a positive or no pregnancy test at baseline. Women of childbearing potential not using a reliable and appropriate contraceptive method. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.) Other active malignancy (i.e. hematologic malignancy, metastatic solid tumor, or resected Stage I-IV solid tumor less than 3 years after resection). Patients with known Gilbert's disease or interstitial pulmonary fibrosis. Patients with prior severe reaction to nonsteroidal anti-inflammatory drugs (NSAIDs), sulfonamides, or celecoxib. Patients with a history of seizure disorders who are receiving antiepileptic medication. Positive malignant cytology of the pleura, pericardium or peritoneum. Uncontrolled diarrhea (National Cancer Institute Common Toxicity Criteria [NCI CTC] greater than or equal to Grade 2). Peripheral neuropathy (NCI CTC greater than or equal to Grade 2). Symptomatic hearing loss, requiring a hearing aid or for which a hearing aid has been suggested by a health professional.
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: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cisplatin/CPT-11/Celecoxib/XRT/Surgery<br>Cisplatin, CPT-11 and Celecoxib With Radiation Therapy and Surgery for Operable Esophageal Cancer | Drug: Cisplatin<br>* Given weekly on weeks 1, 2, 4 and 5 during radiation therapy.<br>Drug: Irinotecan<br>* Given weekly on weeks 1, 2, 4 and 5 during radiation therapy<br>* Other names: CPT-11;Drug: Celecoxib<br>* Given twice daily 3 days prior to radiation and up until one week prior to surgery. It will then be started again once the participant is released from the hospital following surgery for 26 weeks.<br>Procedure: Radiation Therapy<br>* 5 days a week for 5-6 weeks<br>Procedure: Esophagectomy<br>* Within 4-8 weeks of chemoradiation therapy<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of combination of chemotherapy, radiation therapy and surgery in resectable esophageal carcinoma | | |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the side effects of chemotherapy and radiation therapy in patients with resectable esophageal carcinoma | | 2 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Esophageal Cancer, Resectable Esophageal Cancer, Radiation Therapy, Celecoxib, Irinotecan, Cisplatin
|
NCT00256477
|
A Controlled Breathing Course for Social & Emotional Health for Vietnam Veterans With Chronic PTSD-RCT
|
The main aim of this project is to evaluate the use of a specific Yoga technique of controlled breathing in Vietnam War Veterans with chronic posttraumatic stress disorder. This method is currently the subject of a United States grant application to formally test American War Veterans from Afghanistan and Iraq. Drs Gerbarg and Brown are collaborating with The Bay Pines Veterans Administration Medical Center in Florida to develop a study of this course for treatment of American veterans returning from Afghanistan and Iraq. Elements of this method have been used on a variety of populations. Whilst this is a multi-component intervention, it is postulated that the most active ingredient in the program is a specific Yoga breathing technique called Sudarshan Kriya (SK).
|
The main aim of this project is to evaluate the use of a specific Yoga technique of controlled breathing in Vietnam War Veterans with chronic posttraumatic stress disorder. This method is currently the subject of a United States grant application to formally test American War Veterans from Afghanistan and Iraq. Drs Gerbarg and Brown are collaborating with The Bay Pines Veterans Administration Medical Center in Florida to develop a study of this course for treatment of American veterans returning from Afghanistan and Iraq. Elements of this method have been used on a variety of populations. Whilst this is a multi-component intervention, it is postulated that the most active ingredient in the program is a specific Yoga breathing technique called Sudarshan Kriya (SK).~This program has been developed by Sri Sri Ravi Shankar, chief yoga teacher and Head of The Art of Living Foundation (Ravishankar 2002). Further, this method has been applied widely for the treatment of Acute Stress Disorder and Posttraumatic Stress Disorder in individual cases (Gerbarg and Brown 2005Direct communication). For example, this controlled breathing program has been reported to have relieved posttraumatic stress disorder (PTSD) in large groups of people affected by mass disasters such as war (Kosovo, Bosnia, Iraq and Sudan) (Biswas 2004; Joseph 2004; Luedemann 2004), terrorism (New York City 9/11) (Anonymous 2001b), (Kashmir, India, Israel) and natural disasters (Gujurat earthquake, 2000) (Anonymous 2001a) Iran flood, Asian Tsunami. This controlled breathing program is reported to have also helped police (Slovenia, India, Washington, DC) and military personnel (Iraq) (cited in Gerbarg and Brown 2004), (Gerbarg 2005Personal communication). Pilot studies conducted by the Principal Investigator using similar techniques showed positive health results for Vietnam Veterans with PTSD in Australia (Carter and Byrne 2004). However, although randomized clinical trials have been performed for depression with good effect
|
A Controlled Breathing Course Promoting Social and Emotional Health for Vietnam Veterans With Chronic Posttraumatic Stress Disorder - A Randomised Controlled Trial
|
Posttraumatic Stress Disorder
|
* Behavioral: Sudarshan KRIYA Breathing Technique
|
Inclusion Criteria:~suffering chronic post traumatic stress disorder tested by CAPS~Vietnam Veteran~Adequate Cognition~Exclusion Criteria:~Inadequate cogition~suicidality~psychosis~substance abuse other than alcohol
|
50 Years
|
70 Years
|
Male
|
Accepts Healthy Volunteers
|
Primary Purpose: Educational/Counseling/Training
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduce the symptoms of PTSD | | |
| Reduce the comorbid conditions of Depression and alcohol dependence | | |
|
Stress Disorders, Traumatic, Stress Disorders, Post-Traumatic, Trauma and Stressor Related Disorders, Mental Disorders
|
| Intervention/Treatment |
| --- |
|Behavioral: Sudarshan KRIYA Breathing Technique|nan|
|
A Controlled Breathing Course for Social & Emotional Health for Vietnam Veterans With Chronic PTSD-RCT
Study Overview
=================
Brief Summary
-----------------
The main aim of this project is to evaluate the use of a specific Yoga technique of controlled breathing in Vietnam War Veterans with chronic posttraumatic stress disorder. This method is currently the subject of a United States grant application to formally test American War Veterans from Afghanistan and Iraq. Drs Gerbarg and Brown are collaborating with The Bay Pines Veterans Administration Medical Center in Florida to develop a study of this course for treatment of American veterans returning from Afghanistan and Iraq. Elements of this method have been used on a variety of populations. Whilst this is a multi-component intervention, it is postulated that the most active ingredient in the program is a specific Yoga breathing technique called Sudarshan Kriya (SK).
Detailed Description
-----------------
The main aim of this project is to evaluate the use of a specific Yoga technique of controlled breathing in Vietnam War Veterans with chronic posttraumatic stress disorder. This method is currently the subject of a United States grant application to formally test American War Veterans from Afghanistan and Iraq. Drs Gerbarg and Brown are collaborating with The Bay Pines Veterans Administration Medical Center in Florida to develop a study of this course for treatment of American veterans returning from Afghanistan and Iraq. Elements of this method have been used on a variety of populations. Whilst this is a multi-component intervention, it is postulated that the most active ingredient in the program is a specific Yoga breathing technique called Sudarshan Kriya (SK). This program has been developed by Sri Sri Ravi Shankar, chief yoga teacher and Head of The Art of Living Foundation (Ravishankar 2002). Further, this method has been applied widely for the treatment of Acute Stress Disorder and Posttraumatic Stress Disorder in individual cases (Gerbarg and Brown 2005Direct communication). For example, this controlled breathing program has been reported to have relieved posttraumatic stress disorder (PTSD) in large groups of people affected by mass disasters such as war (Kosovo, Bosnia, Iraq and Sudan) (Biswas 2004; Joseph 2004; Luedemann 2004), terrorism (New York City 9/11) (Anonymous 2001b), (Kashmir, India, Israel) and natural disasters (Gujurat earthquake, 2000) (Anonymous 2001a) Iran flood, Asian Tsunami. This controlled breathing program is reported to have also helped police (Slovenia, India, Washington, DC) and military personnel (Iraq) (cited in Gerbarg and Brown 2004), (Gerbarg 2005Personal communication). Pilot studies conducted by the Principal Investigator using similar techniques showed positive health results for Vietnam Veterans with PTSD in Australia (Carter and Byrne 2004). However, although randomized clinical trials have been performed for depression with good effect
Official Title
-----------------
A Controlled Breathing Course Promoting Social and Emotional Health for Vietnam Veterans With Chronic Posttraumatic Stress Disorder - A Randomised Controlled Trial
Conditions
-----------------
Posttraumatic Stress Disorder
Intervention / Treatment
-----------------
* Behavioral: Sudarshan KRIYA Breathing Technique
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: suffering chronic post traumatic stress disorder tested by CAPS Vietnam Veteran Adequate Cognition Exclusion Criteria: Inadequate cogition suicidality psychosis substance abuse other than alcohol
Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Educational/Counseling/Training
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single
Arms and Interventions
| Intervention/Treatment |
| --- |
|Behavioral: Sudarshan KRIYA Breathing Technique|nan|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduce the symptoms of PTSD | | |
| Reduce the comorbid conditions of Depression and alcohol dependence | | |
|
||
NCT01736852
|
Evaluation of CRB in PROM Patients
|
The CRB study is designed to study the safety and effectiveness of the Cook Cervical Ripening Balloon (CRB) for the induction of labor in term and near-term patients with premature rupture of membranes (PROM).
|
Randomized Study to Compare the Cook Cervical Ripening Balloon (CRB) Plus Pitocin to Pitocin Alone in Premature Rupture of Membranes (PROM) Patients
|
Premature Rupture of Fetal Membranes
|
* Device: CRB
* Drug: Pitocin
|
Inclusion Criteria:~PROM not in labor~Exclusion Criteria:~Contraindication to vaginal delivery~Contraindication to labor induction~Abnormal fetal heart-rate patterns~Maternal heart disease~Severe maternal hypertension~Pelvic structural abnormality
|
18 Years
| null |
Female
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of Labor | Time, in minutes, from the start of labor induction through delivery | Start of labor induction through delivery, an expected average of 6 hours |
| Incidence of Infection | number of patients with chorioamnionitis | Through hospital discharge, an expected average of 3 days |
|
Premature Rupture of Membrane (Pregnancy), PROM, Cervical Ripening, Induced Labor
|
Oxytocin, Oxytocics, Reproductive Control Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRB plus Pitocin<br> | Device: CRB<br>* Labor induction using the CRB<br>Drug: Pitocin<br>* Labor induction using Pitocin<br>|
| Active Comparator: Pitocin<br> | Drug: Pitocin<br>* Labor induction using Pitocin<br>|
|
Evaluation of CRB in PROM Patients
Study Overview
=================
Brief Summary
-----------------
The CRB study is designed to study the safety and effectiveness of the Cook Cervical Ripening Balloon (CRB) for the induction of labor in term and near-term patients with premature rupture of membranes (PROM).
Official Title
-----------------
Randomized Study to Compare the Cook Cervical Ripening Balloon (CRB) Plus Pitocin to Pitocin Alone in Premature Rupture of Membranes (PROM) Patients
Conditions
-----------------
Premature Rupture of Fetal Membranes
Intervention / Treatment
-----------------
* Device: CRB
* Drug: Pitocin
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: PROM not in labor Exclusion Criteria: Contraindication to vaginal delivery Contraindication to labor induction Abnormal fetal heart-rate patterns Maternal heart disease Severe maternal hypertension Pelvic structural abnormality
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRB plus Pitocin<br> | Device: CRB<br>* Labor induction using the CRB<br>Drug: Pitocin<br>* Labor induction using Pitocin<br>|
| Active Comparator: Pitocin<br> | Drug: Pitocin<br>* Labor induction using Pitocin<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of Labor | Time, in minutes, from the start of labor induction through delivery | Start of labor induction through delivery, an expected average of 6 hours |
| Incidence of Infection | number of patients with chorioamnionitis | Through hospital discharge, an expected average of 3 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Premature Rupture of Membrane (Pregnancy), PROM, Cervical Ripening, Induced Labor
|
||
NCT00635479
|
Role of Vacuum Assisted Closure (VAC) Device in Postoperative Management of Pelvic and Acetabular Fractures
|
The purpose of this research is to study the efficacy and cost effectiveness of the VAC device in comparison to traditional gauze wound dressing in pelvic, acetabular and hip fractures, specifically to see if there is a reduction in the incidence of post operative surgical wound drainage, infections, and hospital stay.
|
Soft tissue injuries are commonly associated with pelvic and acetabular injuries and additional tissue injury occurs during surgery. Post operative wound drainage, infections and prolonged hospital stay are a common problem during postoperative care. Traditional treatment is dressing of the surgical wound with different conventional dressings.~Use of negative pressure wound therapy has been shown to be beneficial in significantly decreasing wound drainage. Stannard et al. reported the results of randomizing 44 patients with lower extremity fractures (including 4 pilon fractures) into either receiving standard post operative dressing versus NPWT (negative pressure wound therapy). His results showed no difference in infection rate or wound breakdown, but did show a significant difference in the drainage time. The NPWT group stopped draining 3 days earlier than the standard dressing group. The use of NPWT has greatly increased over the years and has been an important adjunct to wound management. These results and anecdotal clinical experience with the use of NPWT (wound VAC) has led us to develop our research question; Does the use of incisional VAC following pelvic &/or acetabular surgery decrease wound complications.~The VAC (KCI USA) device is relatively new device that utilizes negative pressure as a treatment modality for soft tissue injuries following high velocity injuries. VAC device exerts intermittent or constant negative pressure and removes excess fluid from the interstitial space and increases perfusion through vessels. Previous VAC studies showed decreased bacterial load after applying VAC device to the infected wounds.~There have been no randomized studies to prove the cost effectiveness and efficacy of VAC device in reducing wound drainage, infections, and prolonged hospital stays in comparison to traditional gauze dressing wound management during post operative management of pelvic and acetabular fractures.~In examining the incidence of wound complications/infections, we can determine if the incisional VAC decreases the need for additional intervention and if there are any patient related factors (i.e. obesity) related to increased risk of wound complications.
|
Role of Vacuum Assisted Closure (VAC) Device in Postoperative Management of Pelvic and Acetabular Fractures
|
Pelvic Fractures, Acetabular Fractures, Hip Fractures
|
* Device: VAC device
* Other: Gauze dressing
|
Inclusion Criteria:~18 years or older~Scheduled for surgical repair of pelvic and/or acetabular fracture~Subject/guardian able to provide informed consent~Exclusion Criteria:~Less than 18 years of age~Subject/guardian unable to provide informed consent
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Wound Infections | | Until wound healed, up to 1 year |
|
Fractures, Pelvic bones, Acetabulum, Hip bones
|
Fractures, Bone, Hip Fractures, Wounds and Injuries, Femoral Fractures, Hip Injuries, Leg Injuries
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VAC Device placement<br>will have the VAC device used for post-operative management of acetabular fractures and pelvic fractures. | Device: VAC device<br>* Vacuum Assisted Closure (VAC) device for surgical incision<br>* Other names: Incisional Vac;|
| Active Comparator: Gauze dressing<br>will receive current traditional surgical wound management with daily dressing changes in post operative management of acetabular fractures and pelvic fractures. | Other: Gauze dressing<br>* Gauze dressing for surgical incision<br>|
|
Role of Vacuum Assisted Closure (VAC) Device in Postoperative Management of Pelvic and Acetabular Fractures
Study Overview
=================
Brief Summary
-----------------
The purpose of this research is to study the efficacy and cost effectiveness of the VAC device in comparison to traditional gauze wound dressing in pelvic, acetabular and hip fractures, specifically to see if there is a reduction in the incidence of post operative surgical wound drainage, infections, and hospital stay.
Detailed Description
-----------------
Soft tissue injuries are commonly associated with pelvic and acetabular injuries and additional tissue injury occurs during surgery. Post operative wound drainage, infections and prolonged hospital stay are a common problem during postoperative care. Traditional treatment is dressing of the surgical wound with different conventional dressings. Use of negative pressure wound therapy has been shown to be beneficial in significantly decreasing wound drainage. Stannard et al. reported the results of randomizing 44 patients with lower extremity fractures (including 4 pilon fractures) into either receiving standard post operative dressing versus NPWT (negative pressure wound therapy). His results showed no difference in infection rate or wound breakdown, but did show a significant difference in the drainage time. The NPWT group stopped draining 3 days earlier than the standard dressing group. The use of NPWT has greatly increased over the years and has been an important adjunct to wound management. These results and anecdotal clinical experience with the use of NPWT (wound VAC) has led us to develop our research question; Does the use of incisional VAC following pelvic &/or acetabular surgery decrease wound complications. The VAC (KCI USA) device is relatively new device that utilizes negative pressure as a treatment modality for soft tissue injuries following high velocity injuries. VAC device exerts intermittent or constant negative pressure and removes excess fluid from the interstitial space and increases perfusion through vessels. Previous VAC studies showed decreased bacterial load after applying VAC device to the infected wounds. There have been no randomized studies to prove the cost effectiveness and efficacy of VAC device in reducing wound drainage, infections, and prolonged hospital stays in comparison to traditional gauze dressing wound management during post operative management of pelvic and acetabular fractures. In examining the incidence of wound complications/infections, we can determine if the incisional VAC decreases the need for additional intervention and if there are any patient related factors (i.e. obesity) related to increased risk of wound complications.
Official Title
-----------------
Role of Vacuum Assisted Closure (VAC) Device in Postoperative Management of Pelvic and Acetabular Fractures
Conditions
-----------------
Pelvic Fractures, Acetabular Fractures, Hip Fractures
Intervention / Treatment
-----------------
* Device: VAC device
* Other: Gauze dressing
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years or older Scheduled for surgical repair of pelvic and/or acetabular fracture Subject/guardian able to provide informed consent Exclusion Criteria: Less than 18 years of age Subject/guardian unable to provide 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?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VAC Device placement<br>will have the VAC device used for post-operative management of acetabular fractures and pelvic fractures. | Device: VAC device<br>* Vacuum Assisted Closure (VAC) device for surgical incision<br>* Other names: Incisional Vac;|
| Active Comparator: Gauze dressing<br>will receive current traditional surgical wound management with daily dressing changes in post operative management of acetabular fractures and pelvic fractures. | Other: Gauze dressing<br>* Gauze dressing for surgical incision<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Wound Infections | | Until wound healed, up to 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fractures, Pelvic bones, Acetabulum, Hip bones
|
|
NCT02667730
|
Correlation Between Acute Analgesia and Long-Term Function Following Ankle Injuries
|
In this 4-arm pragmatic randomized control trial, the investigators hope to decipher whether the use of non-opioid analgesics (naproxen, celecoxib, acetaminophen) in addition to standardized physiotherapy during the acute phase of grade I-II ankle injuries will result in functional differences compared to standardized physiotherapy alone
|
Background Ankle sprains occur frequently in the Canadian Armed Forces (CAF) population and account for a significant proportion of lost work time. Equally significant is the use of analgesics (NSAID or non-NSAID) (NSAID = non steroidal anti-inflammatory drug) in the CAF population. Existing literature suggests that the rate and extent of soft tissue healing may be adversely affected by use of some analgesics, particularly non-steroidal anti-inflammatory agents (NSAIDs), when these are used immediately following joint injury. There have been two postulated mechanisms for this observation: the first being that inflammatory markers are required in the regeneration process; the second is that the diminished pain level as a result of analgesic use encourages overuse of the injured tissue. Unfortunately, the science is far from conclusive, since much of it is derived based on isolated exercises, conducted in experimental settings, in older populations, or extrapolated from biomarkers that have not been validated for clinical relevance. While there is no current standard of practice regarding the use of pain relievers following ankle injury, this practice continues to be widespread in the CAF.~Goal The proposed study aims to clarify whether three commonly used non-opioid pain relievers provide additional benefit or delay improvement in ankle function following mild ankle sprains, when compared to standardized physiotherapy treatment alone. The three agents investigated will be 1) the non-steroid anti-inflammatory drug naproxen, 2) the selective anti-inflammatory celecoxib, and 3) the centrally-acting analgesic acetaminophen.~Methods Patients presenting to the health clinic at Garrison Petawawa with acute ankle injuries will be screened for study eligibility. All individuals who elect to participate in this study will be referred for standardized physiotherapy treatment, which will be administered according to study protocol. Participants will also be randomized to one of four analgesic treatment groups (i.e., naproxen, celecoxib, acetaminophen, or non-pharmacological measures only), with stratification for grade of ankle injury. Physiotherapists who are blinded to analgesic treatment allocation will evaluate participants' ankle function at 72 hours, 2 weeks, 3 months and 1 year post-injury, using previously validated tests. Pharmacists will assess response to drug therapy, side effects, and use of rescue medications at day 7 following enrollment. Occurrence of repeat ankle injuries and health resource consumption (i.e., specialist visits and diagnostic imaging) will also be assessed for the year following index injury.~Risks This study is intended to be low risk to participants as it is designed to closely mirror existing practices for such injuries. All medications used in this study are indicated for soft tissue injuries and their respective dosages/frequencies/durations aligned with manufacturer recommendations. The physiotherapy intervention was developed by Dr. Eric Robitaille. It has been used in previous studies and is currently in use in the CAF. The investigators do not expect the risk of injury to be higher than that associated with existing practices for ankle injuries.~Benefits Participants are expected to benefit from the direct application of a standardized physiotherapy treatment protocol for overall management of their condition as well as the pain relief from the analgesic options. The results of this study are expected to generate new information that can be readily applied to patient care, specifically in treating a frequently-occurring soft tissue injury in the CAF population.
|
Correlation Between Acute Analgesia and Long-Term Function Following Ankle
|
Ligament Injury
|
* Drug: Acetaminophen
* Drug: Naproxen
* Drug: Celecoxib
* Other: physiotherapy only
|
Inclusion Criteria:~Acquired acute ankle injury (injured less than 48 hours ago);~Clinical diagnosis of a Grade I or II ankle sprain~Is eligible to receive comprehensive medical care from Garrison Petawawa~Exclusion Criteria:~Diagnosis of ankle fracture or ligament rupture~Has planned release from the Canadian Armed Forces within one year;~Documented restrictions on military duties~Has known intolerance or documented adverse reaction to acetaminophen or naproxen or celecoxib~Documented history of liver or kidney problems~pregnant or breastfeeding
|
17 Years
|
60 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ankle Function on FAAM | Foot and Ankle Abilities Measure | 3 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain on visual analogue scale (VAS) | visual analogue scale | 3 months |
| Mobility on Wall Lunge | wall lunge test for ankle mobility | 3 months |
| Laxity on anterior drawer test | test for laxity | 3 months |
| Proprioception on SEBT | star excursion balance test | 3 months |
| composite of health resource consumption | # of orthopedic specialist consults, diagnostics, patient encounters for MSK reasons, # of days off work | 1 year |
|
Acetaminophen, Celecoxib, Naproxen, Analgesics, Non-Narcotic, Analgesics, Sensory System Agents, Peripheral Nervous System Agents, Physiological Effects of Drugs, Antipyretics, Anti-Inflammatory Agents, Non-Steroidal, Anti-Inflammatory Agents, Antirheumatic Agents, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Gout Suppressants
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Physiotherapy only<br>This group will receive non-pharmacological advice and physiotherapy only | Other: physiotherapy only<br>* physiotherapy only (no drug)<br>|
| Experimental: Acetaminophen + physiotherapy<br>This group will receive acetaminophen 500mg 4 times daily for 7 days in addition to standardized physiotherapy | Drug: Acetaminophen<br>* Acetaminophen 500 mg four times daily for 7 days<br>* Other names: tylenol;Other: physiotherapy only<br>* physiotherapy only (no drug)<br>|
| Experimental: Naproxen + physiotherapy<br>This group will receive naproxen 500mg twice daily for 7 days in addition to standardized physiotherapy | Drug: Naproxen<br>* naproxen 500mg twice daily for 7 days<br>Other: physiotherapy only<br>* physiotherapy only (no drug)<br>|
| Experimental: Celecoxib + physiotherapy<br>This group will receive celecoxib 100mg twice daily for 7 days in addition to standardized physiotherapy | Drug: Celecoxib<br>* celecoxib 100mg twice daily<br>* Other names: celebrex;Other: physiotherapy only<br>* physiotherapy only (no drug)<br>|
|
Correlation Between Acute Analgesia and Long-Term Function Following Ankle Injuries
Study Overview
=================
Brief Summary
-----------------
In this 4-arm pragmatic randomized control trial, the investigators hope to decipher whether the use of non-opioid analgesics (naproxen, celecoxib, acetaminophen) in addition to standardized physiotherapy during the acute phase of grade I-II ankle injuries will result in functional differences compared to standardized physiotherapy alone
Detailed Description
-----------------
Background Ankle sprains occur frequently in the Canadian Armed Forces (CAF) population and account for a significant proportion of lost work time. Equally significant is the use of analgesics (NSAID or non-NSAID) (NSAID = non steroidal anti-inflammatory drug) in the CAF population. Existing literature suggests that the rate and extent of soft tissue healing may be adversely affected by use of some analgesics, particularly non-steroidal anti-inflammatory agents (NSAIDs), when these are used immediately following joint injury. There have been two postulated mechanisms for this observation: the first being that inflammatory markers are required in the regeneration process; the second is that the diminished pain level as a result of analgesic use encourages overuse of the injured tissue. Unfortunately, the science is far from conclusive, since much of it is derived based on isolated exercises, conducted in experimental settings, in older populations, or extrapolated from biomarkers that have not been validated for clinical relevance. While there is no current standard of practice regarding the use of pain relievers following ankle injury, this practice continues to be widespread in the CAF. Goal The proposed study aims to clarify whether three commonly used non-opioid pain relievers provide additional benefit or delay improvement in ankle function following mild ankle sprains, when compared to standardized physiotherapy treatment alone. The three agents investigated will be 1) the non-steroid anti-inflammatory drug naproxen, 2) the selective anti-inflammatory celecoxib, and 3) the centrally-acting analgesic acetaminophen. Methods Patients presenting to the health clinic at Garrison Petawawa with acute ankle injuries will be screened for study eligibility. All individuals who elect to participate in this study will be referred for standardized physiotherapy treatment, which will be administered according to study protocol. Participants will also be randomized to one of four analgesic treatment groups (i.e., naproxen, celecoxib, acetaminophen, or non-pharmacological measures only), with stratification for grade of ankle injury. Physiotherapists who are blinded to analgesic treatment allocation will evaluate participants' ankle function at 72 hours, 2 weeks, 3 months and 1 year post-injury, using previously validated tests. Pharmacists will assess response to drug therapy, side effects, and use of rescue medications at day 7 following enrollment. Occurrence of repeat ankle injuries and health resource consumption (i.e., specialist visits and diagnostic imaging) will also be assessed for the year following index injury. Risks This study is intended to be low risk to participants as it is designed to closely mirror existing practices for such injuries. All medications used in this study are indicated for soft tissue injuries and their respective dosages/frequencies/durations aligned with manufacturer recommendations. The physiotherapy intervention was developed by Dr. Eric Robitaille. It has been used in previous studies and is currently in use in the CAF. The investigators do not expect the risk of injury to be higher than that associated with existing practices for ankle injuries. Benefits Participants are expected to benefit from the direct application of a standardized physiotherapy treatment protocol for overall management of their condition as well as the pain relief from the analgesic options. The results of this study are expected to generate new information that can be readily applied to patient care, specifically in treating a frequently-occurring soft tissue injury in the CAF population.
Official Title
-----------------
Correlation Between Acute Analgesia and Long-Term Function Following Ankle
Conditions
-----------------
Ligament Injury
Intervention / Treatment
-----------------
* Drug: Acetaminophen
* Drug: Naproxen
* Drug: Celecoxib
* Other: physiotherapy only
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Acquired acute ankle injury (injured less than 48 hours ago); Clinical diagnosis of a Grade I or II ankle sprain Is eligible to receive comprehensive medical care from Garrison Petawawa Exclusion Criteria: Diagnosis of ankle fracture or ligament rupture Has planned release from the Canadian Armed Forces within one year; Documented restrictions on military duties Has known intolerance or documented adverse reaction to acetaminophen or naproxen or celecoxib Documented history of liver or kidney problems pregnant or breastfeeding
Ages Eligible for Study
-----------------
Minimum Age: 17 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Physiotherapy only<br>This group will receive non-pharmacological advice and physiotherapy only | Other: physiotherapy only<br>* physiotherapy only (no drug)<br>|
| Experimental: Acetaminophen + physiotherapy<br>This group will receive acetaminophen 500mg 4 times daily for 7 days in addition to standardized physiotherapy | Drug: Acetaminophen<br>* Acetaminophen 500 mg four times daily for 7 days<br>* Other names: tylenol;Other: physiotherapy only<br>* physiotherapy only (no drug)<br>|
| Experimental: Naproxen + physiotherapy<br>This group will receive naproxen 500mg twice daily for 7 days in addition to standardized physiotherapy | Drug: Naproxen<br>* naproxen 500mg twice daily for 7 days<br>Other: physiotherapy only<br>* physiotherapy only (no drug)<br>|
| Experimental: Celecoxib + physiotherapy<br>This group will receive celecoxib 100mg twice daily for 7 days in addition to standardized physiotherapy | Drug: Celecoxib<br>* celecoxib 100mg twice daily<br>* Other names: celebrex;Other: physiotherapy only<br>* physiotherapy only (no drug)<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ankle Function on FAAM | Foot and Ankle Abilities Measure | 3 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain on visual analogue scale (VAS) | visual analogue scale | 3 months |
| Mobility on Wall Lunge | wall lunge test for ankle mobility | 3 months |
| Laxity on anterior drawer test | test for laxity | 3 months |
| Proprioception on SEBT | star excursion balance test | 3 months |
| composite of health resource consumption | # of orthopedic specialist consults, diagnostics, patient encounters for MSK reasons, # of days off work | 1 year |
|
|
NCT04018677
|
TOGETHER: Track Outcomes and Guidance, Technology for Health and Effective Resources
|
The goal of this project is to iteratively develop and test a TOGETHER pilot mobile app product in preparation for commercialization. TOGETHER is a mobile application on a smart software system that informal caregivers can use to develop and implement home-based care for cancer patients/survivors.~The Technical Objectives are to:~Establish the project team and obtain stakeholder feedback on what to include in the product.~Evaluate IT customization requirements and HIPAA compliance security, and privacy protocols.~Develop a prototype to show NCI and then a pilot version for beta and usability testing among stakeholders.~Enhance interoperability and test integration into health system(s) - if feasible.~Develop user support documentation for stakeholders.
|
TOGETHER: Track Outcomes and Guidance, Technology for Health and Effective Resources
|
Cancer
|
* Behavioral: Use of TOGETHERCare app
|
Inclusion Criteria:~Adults (aged 18 years or older) who are either:~Cancer patient/survivor receiving care or with plans to transition to care in the community setting.~Caregiver of cancer patient/survivor receiving care or with plans to transition to care in the community setting.~Clinician of cancer patient/survivor receiving care or with plans to transition to care in the community setting.~Cancer patient is a patient of Stanford Health Care.~Patient, Caregiver, and Clinician are willing to be connected on the app.~Have a smartphone and data plan that allows for app installation and usage.~Must speak, read and write in English, because all study materials and communication will be in English.~Exclusion Criteria:~Patient does not have a cancer diagnosis.~Cancer patient/survivor is not receiving care or does not have plans to transition to care in the community setting.~Cancer patient is not a patient of Stanford Health Care.~Patient, Caregiver, and Clinician are not willing to be connected on the app.~Unable to speak, read and write in English.~Does not have a smartphone nor data plan that allows for app installation and usage
|
18 Years
| null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess user experience with TOGETHER app | User experiences will be assessed by measuring overall experiences. | 1 year |
| Assess user experience with TOGETHER app | User experiences will be assessed by measuring module recommendation. | 1 year |
| Assess user experience with TOGETHER app | User experiences will be assessed by measuring dynamics/flow of app use, module recommendation, and general demographics. | 1 year |
| Assess user experience with TOGETHER app | User experiences will be assessed by measuring problems with app use. | 1 year |
| Assess caregiver's experience with TOGETHER app | Caregiver's experience with TOGETHER app will be assessed for clarity of documentation. | 1 year |
| User documentation feedback | General feedback/recommendations for the app, including user documentation feedback. | 1 year |
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Beta Testing<br>For the beta testing, input will be provided by cancer patient/survivor, caregivers, and clinicians. TOGETHER app will be downloaded on smart phone. Subjects will be asked to answer questions and/or perform activities on his/her smartphone device. Project information will include responses to surveys and giving additional feedback on app user experience. | Behavioral: Use of TOGETHERCare app<br>* TOGETHERCare (Medable Inc.) is a mobile software application on a smart software system that informal caregivers can use to develop and implement home-based care for cancer patients/survivors. It is intended to improve the care experience by helping to alleviate the cancer care-giving burden and facilitate communication with patients' healthcare teams by centering the conversation around a care plan.<br>|
| Experimental: Usability testing<br>For the usability testing, caregivers will be the primary type of stakeholder providing input. TOGETHER app will be downloaded on smart phone. Subjects will be asked to answer questions and/or perform activities on his/her smartphone device. Project information will include responses to surveys and giving additional feedback on app user experience. | Behavioral: Use of TOGETHERCare app<br>* TOGETHERCare (Medable Inc.) is a mobile software application on a smart software system that informal caregivers can use to develop and implement home-based care for cancer patients/survivors. It is intended to improve the care experience by helping to alleviate the cancer care-giving burden and facilitate communication with patients' healthcare teams by centering the conversation around a care plan.<br>|
|
TOGETHER: Track Outcomes and Guidance, Technology for Health and Effective Resources
Study Overview
=================
Brief Summary
-----------------
The goal of this project is to iteratively develop and test a TOGETHER pilot mobile app product in preparation for commercialization. TOGETHER is a mobile application on a smart software system that informal caregivers can use to develop and implement home-based care for cancer patients/survivors. The Technical Objectives are to: Establish the project team and obtain stakeholder feedback on what to include in the product. Evaluate IT customization requirements and HIPAA compliance security, and privacy protocols. Develop a prototype to show NCI and then a pilot version for beta and usability testing among stakeholders. Enhance interoperability and test integration into health system(s) - if feasible. Develop user support documentation for stakeholders.
Official Title
-----------------
TOGETHER: Track Outcomes and Guidance, Technology for Health and Effective Resources
Conditions
-----------------
Cancer
Intervention / Treatment
-----------------
* Behavioral: Use of TOGETHERCare app
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults (aged 18 years or older) who are either: Cancer patient/survivor receiving care or with plans to transition to care in the community setting. Caregiver of cancer patient/survivor receiving care or with plans to transition to care in the community setting. Clinician of cancer patient/survivor receiving care or with plans to transition to care in the community setting. Cancer patient is a patient of Stanford Health Care. Patient, Caregiver, and Clinician are willing to be connected on the app. Have a smartphone and data plan that allows for app installation and usage. Must speak, read and write in English, because all study materials and communication will be in English. Exclusion Criteria: Patient does not have a cancer diagnosis. Cancer patient/survivor is not receiving care or does not have plans to transition to care in the community setting. Cancer patient is not a patient of Stanford Health Care. Patient, Caregiver, and Clinician are not willing to be connected on the app. Unable to speak, read and write in English. Does not have a smartphone nor data plan that allows for app installation and usage
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: Supportive Care
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Beta Testing<br>For the beta testing, input will be provided by cancer patient/survivor, caregivers, and clinicians. TOGETHER app will be downloaded on smart phone. Subjects will be asked to answer questions and/or perform activities on his/her smartphone device. Project information will include responses to surveys and giving additional feedback on app user experience. | Behavioral: Use of TOGETHERCare app<br>* TOGETHERCare (Medable Inc.) is a mobile software application on a smart software system that informal caregivers can use to develop and implement home-based care for cancer patients/survivors. It is intended to improve the care experience by helping to alleviate the cancer care-giving burden and facilitate communication with patients' healthcare teams by centering the conversation around a care plan.<br>|
| Experimental: Usability testing<br>For the usability testing, caregivers will be the primary type of stakeholder providing input. TOGETHER app will be downloaded on smart phone. Subjects will be asked to answer questions and/or perform activities on his/her smartphone device. Project information will include responses to surveys and giving additional feedback on app user experience. | Behavioral: Use of TOGETHERCare app<br>* TOGETHERCare (Medable Inc.) is a mobile software application on a smart software system that informal caregivers can use to develop and implement home-based care for cancer patients/survivors. It is intended to improve the care experience by helping to alleviate the cancer care-giving burden and facilitate communication with patients' healthcare teams by centering the conversation around a care plan.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess user experience with TOGETHER app | User experiences will be assessed by measuring overall experiences. | 1 year |
| Assess user experience with TOGETHER app | User experiences will be assessed by measuring module recommendation. | 1 year |
| Assess user experience with TOGETHER app | User experiences will be assessed by measuring dynamics/flow of app use, module recommendation, and general demographics. | 1 year |
| Assess user experience with TOGETHER app | User experiences will be assessed by measuring problems with app use. | 1 year |
| Assess caregiver's experience with TOGETHER app | Caregiver's experience with TOGETHER app will be assessed for clarity of documentation. | 1 year |
| User documentation feedback | General feedback/recommendations for the app, including user documentation feedback. | 1 year |
|
||||
NCT02999022
|
Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial (LiFT)
|
This is a study designed to see if a low dose of Lithium treatment, taken for 2 weeks, can improve fracture healing and improve patients' function and productivity.
|
Despite the success of traditional treatments for broken bones (surgery, immobilization, or both) 10% of fractures do not heal or take longer than normal to heal. This can have a significant effect on a patient's function and productivity, as well as on healthcare expenditures. Very few advances in fracture healing have been made, despite the need for new approaches to fracture treatment. This study proposes a simple, economical, and non-invasive approach to complement traditional fracture treatment that could decrease healing time and reduce the incidence of delayed healing. The investigators think that this can improve health outcomes for patients and reduce health care costs for the healthcare system in general. The goal is to see if a low-dose of Lithium treatment can have a positive effect on fracture healing and can reduce pain and improve function in patients who have broken a bone.~The LiFT study is a participant, surgeon and observer blinded single-centre randomized (1:1), controlled, superiority trial with 2 parallel groups. A minimization procedure will stratify participants based on the fractured long bone (clavicle, humerus, femur or tibia/fibula) and smoking.~Participants will be randomized to 1 of 2 groups: lithium capsules or placebo. The Lithium/placebo will be taken daily for 2 weeks, starting 2 weeks after the fracture occurs (or 2 weeks after surgery if the participant is treated with surgery).
|
Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial
|
Fractures
|
* Drug: Lithium Carbonate
* Drug: Lactose Placebo
|
Inclusion Criteria:~Age 18-55 years.~ASA (American Society of Anesthesiologists) ≤ 2 class (healthy) prior to injury.~Diaphyseal fracture of the humerus, femur or combined tibia/fibula (OTA diaphyseal subclass 2A or B), and clavicle (OTA diaphyseal subclass B1 or B2), with or without nerve injury.~Fracture that is primarily closed or open fracture that has complete wound coverage.~Randomization ≤14 days from injury or surgery (for surgical patients).~Fractures treated surgically or nonsurgically by endochondral/secondary bone healing.~For surgical patients, surgery must be within 14 days of injury.~Exclusion Criteria:~Currently pregnant or breastfeeding.~Any past or current malignancy that, in the opinion of an investigator, is not medically controlled.~Metabolic bone disease based on clinical history that, in the opinion of an investigator, is not medically controlled.~Autoimmune disease that, in the opinion of an investigator, is not medically controlled.~Hypothyroidism based on clinical history that, in the opinion of an investigator, is not medically controlled.~Renal impairment based on clinical history.~Past allergy or adverse reaction to Lithium.~Lactose intolerance.~Fractures surgically treated with absolute stability/primary bone healing.~Isolated tibia or isolated fibula fracture.~Currently taking Lithium or anti-psychotic or anti-seizure medication for the treatment of these conditions or at the discretion of an investigator.~Inability to comply with study protocol, in the opinion of the investigator(s).~Participation in another interventional clinical trial, at the discretion of the principal investigator.~Use of concomitant ultrasound or other bone stimulation device.
|
18 Years
|
55 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| radiographic healing of fracture | radiographic healing using the RUST score at 8 weeks | 8 weeks after injury (non-surgical participants) or 8 weeks after surgery (surgical participants) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| radiographic union of fracture | time to radiographic union using the RUST score | 4, 6, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 12, and 24 weeks after surgery (surgical participants) |
| visual analogue pain score | changes from baseline in participant-reported average pain in past week as measured on a visual analogue scale from 0-10 where 0 is no pain and 10 is extreme pain | baseline then 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or baseline then 4, 6, 8, 12, and 24 weeks after surgery (surgical participants) |
| physical function | changes in participant-reported function from baseline as measured on the RAND SF36 questionnaire | baseline then 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or baseline then 4, 6, 8, 12, and 24 weeks after surgery (surgical participants) |
| NSAID use | to track participant-reported use of non-steroidal anti-inflammatory medication and measure changes over the course of the study | baseline then 3, 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or baseline then 3, 4, 6, 8, 12, and 24 weeks after surgery (surgical participants) |
| re-operation (after initial fracture management) | surgery required after initial fracture management | 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 8, 12, and 24 weeks after surgery (surgical participants) |
| adverse events | the number and type of adverse events occuring after the first dose of lithium/placebo and until the 6-week visit will be collected and reported according to local and national rules and regulations | 2-6 weeks after injury (non-surgical participants) or 2-6 weeks after surgery (surgical participants) |
|
bone fractures, bony callus, fractures, bone, lithium, lithium carbonate, osteogenesis, bone development, fracture healing, fracture repair
|
Lithium Carbonate, Antidepressive Agents, Psychotropic Drugs, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action, Antimanic Agents, Tranquilizing Agents, Central Nervous System Depressants, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lithium carbonate<br>Lithium carbonate 300mg capsule; once per day for 2 weeks. | Drug: Lithium Carbonate<br>* Intervention begins 14 days after injury for non-surgical participants and 2 weeks after surgery for participants who have surgical treatment of their fractures.<br>* Other names: Lithium;|
| Placebo Comparator: Lactose placebo<br>Lactose placebo capsule; once per day for 2 weeks. | Drug: Lactose Placebo<br>* Intervention begins 14 days after injury for non-surgical participants and 2 weeks after surgery for participants who have surgical treatment of their fractures.<br>* Other names: placebo;|
|
Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial (LiFT)
Study Overview
=================
Brief Summary
-----------------
This is a study designed to see if a low dose of Lithium treatment, taken for 2 weeks, can improve fracture healing and improve patients' function and productivity.
Detailed Description
-----------------
Despite the success of traditional treatments for broken bones (surgery, immobilization, or both) 10% of fractures do not heal or take longer than normal to heal. This can have a significant effect on a patient's function and productivity, as well as on healthcare expenditures. Very few advances in fracture healing have been made, despite the need for new approaches to fracture treatment. This study proposes a simple, economical, and non-invasive approach to complement traditional fracture treatment that could decrease healing time and reduce the incidence of delayed healing. The investigators think that this can improve health outcomes for patients and reduce health care costs for the healthcare system in general. The goal is to see if a low-dose of Lithium treatment can have a positive effect on fracture healing and can reduce pain and improve function in patients who have broken a bone. The LiFT study is a participant, surgeon and observer blinded single-centre randomized (1:1), controlled, superiority trial with 2 parallel groups. A minimization procedure will stratify participants based on the fractured long bone (clavicle, humerus, femur or tibia/fibula) and smoking. Participants will be randomized to 1 of 2 groups: lithium capsules or placebo. The Lithium/placebo will be taken daily for 2 weeks, starting 2 weeks after the fracture occurs (or 2 weeks after surgery if the participant is treated with surgery).
Official Title
-----------------
Lithium for Fracture Treatment: a Double Blind Randomized Controlled Trial
Conditions
-----------------
Fractures
Intervention / Treatment
-----------------
* Drug: Lithium Carbonate
* Drug: Lactose Placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-55 years. ASA (American Society of Anesthesiologists) ≤ 2 class (healthy) prior to injury. Diaphyseal fracture of the humerus, femur or combined tibia/fibula (OTA diaphyseal subclass 2A or B), and clavicle (OTA diaphyseal subclass B1 or B2), with or without nerve injury. Fracture that is primarily closed or open fracture that has complete wound coverage. Randomization ≤14 days from injury or surgery (for surgical patients). Fractures treated surgically or nonsurgically by endochondral/secondary bone healing. For surgical patients, surgery must be within 14 days of injury. Exclusion Criteria: Currently pregnant or breastfeeding. Any past or current malignancy that, in the opinion of an investigator, is not medically controlled. Metabolic bone disease based on clinical history that, in the opinion of an investigator, is not medically controlled. Autoimmune disease that, in the opinion of an investigator, is not medically controlled. Hypothyroidism based on clinical history that, in the opinion of an investigator, is not medically controlled. Renal impairment based on clinical history. Past allergy or adverse reaction to Lithium. Lactose intolerance. Fractures surgically treated with absolute stability/primary bone healing. Isolated tibia or isolated fibula fracture. Currently taking Lithium or anti-psychotic or anti-seizure medication for the treatment of these conditions or at the discretion of an investigator. Inability to comply with study protocol, in the opinion of the investigator(s). Participation in another interventional clinical trial, at the discretion of the principal investigator. Use of concomitant ultrasound or other bone stimulation device.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 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: Lithium carbonate<br>Lithium carbonate 300mg capsule; once per day for 2 weeks. | Drug: Lithium Carbonate<br>* Intervention begins 14 days after injury for non-surgical participants and 2 weeks after surgery for participants who have surgical treatment of their fractures.<br>* Other names: Lithium;|
| Placebo Comparator: Lactose placebo<br>Lactose placebo capsule; once per day for 2 weeks. | Drug: Lactose Placebo<br>* Intervention begins 14 days after injury for non-surgical participants and 2 weeks after surgery for participants who have surgical treatment of their fractures.<br>* Other names: placebo;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| radiographic healing of fracture | radiographic healing using the RUST score at 8 weeks | 8 weeks after injury (non-surgical participants) or 8 weeks after surgery (surgical participants) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| radiographic union of fracture | time to radiographic union using the RUST score | 4, 6, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 12, and 24 weeks after surgery (surgical participants) |
| visual analogue pain score | changes from baseline in participant-reported average pain in past week as measured on a visual analogue scale from 0-10 where 0 is no pain and 10 is extreme pain | baseline then 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or baseline then 4, 6, 8, 12, and 24 weeks after surgery (surgical participants) |
| physical function | changes in participant-reported function from baseline as measured on the RAND SF36 questionnaire | baseline then 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or baseline then 4, 6, 8, 12, and 24 weeks after surgery (surgical participants) |
| NSAID use | to track participant-reported use of non-steroidal anti-inflammatory medication and measure changes over the course of the study | baseline then 3, 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or baseline then 3, 4, 6, 8, 12, and 24 weeks after surgery (surgical participants) |
| re-operation (after initial fracture management) | surgery required after initial fracture management | 4, 6, 8, 12, and 24 weeks after injury (non-surgical participants) or 4, 6, 8, 12, and 24 weeks after surgery (surgical participants) |
| adverse events | the number and type of adverse events occuring after the first dose of lithium/placebo and until the 6-week visit will be collected and reported according to local and national rules and regulations | 2-6 weeks after injury (non-surgical participants) or 2-6 weeks after surgery (surgical participants) |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bone fractures, bony callus, fractures, bone, lithium, lithium carbonate, osteogenesis, bone development, fracture healing, fracture repair
|
NCT04183322
|
PCV13 in Non-pregnant Papua New Guinean Women
|
This is an observational study to determine the reactogenicity and immunogenicity of pneumococcal conjugate vaccine in non-pregnant women of reproductive age in Papua New Guinea.
|
Reactogenicity and Immunogenicity of Pneumococcal Conjugate Vaccination in Non-pregnant Papua New Guinean Women
|
Pneumococcal Infections
|
* Biological: 13-valent pneumococcal conjugate vaccine
|
Inclusion Criteria:~Healthy~Non-pregnant~18-45 years old~Exclusion Criteria:~Known hypersensitivity to any vaccine component~Known/suspected to be immunocompromised~Receipt of corticosteroids ≤30 days before~Pregnant (pregnancy tests will be performed)~Not being well at the time of vaccination~Plan to travel out of the area in the month post-vaccination
|
18 Years
|
45 Years
|
Female
| null |
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Mean Fold Increase (MFI; and 95% CI) in vaccine-serotype specific IgG concentrations at 28 days after compared to baseline (before vaccination) | 28 days |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactogenicity | Proportion (% & 95% CI) of participants with local and systemic side effects 24-48 hours after vaccination | 24-48 hours after vaccination |
| Adverse events | Proportion (% & 95% CI) of participants reporting any unexpected adverse effect (AE) during 28 days after vaccination | 28 days |
|
Pneumococcal conjugate vaccine, PCV, Reactogenicity, Immunogenicity, Women childbearing age
|
Heptavalent Pneumococcal Conjugate Vaccine, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women of childbearing age<br>Healthy non-pregnant women between 18 and 45 years old living in Goroka, Papua New Guinea, will receive one dose of 13-valent pneumococcal conjugate vaccine (PCV). | Biological: 13-valent pneumococcal conjugate vaccine<br> <br> * Other names: Prevenar13;|
|
PCV13 in Non-pregnant Papua New Guinean Women
Study Overview
=================
Brief Summary
-----------------
This is an observational study to determine the reactogenicity and immunogenicity of pneumococcal conjugate vaccine in non-pregnant women of reproductive age in Papua New Guinea.
Official Title
-----------------
Reactogenicity and Immunogenicity of Pneumococcal Conjugate Vaccination in Non-pregnant Papua New Guinean Women
Conditions
-----------------
Pneumococcal Infections
Intervention / Treatment
-----------------
* Biological: 13-valent pneumococcal conjugate vaccine
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Non-pregnant 18-45 years old Exclusion Criteria: Known hypersensitivity to any vaccine component Known/suspected to be immunocompromised Receipt of corticosteroids ≤30 days before Pregnant (pregnancy tests will be performed) Not being well at the time of vaccination Plan to travel out of the area in the month post-vaccination
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years
Sexes Eligible for Study
-----------------
Female
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women of childbearing age<br>Healthy non-pregnant women between 18 and 45 years old living in Goroka, Papua New Guinea, will receive one dose of 13-valent pneumococcal conjugate vaccine (PCV). | Biological: 13-valent pneumococcal conjugate vaccine<br> <br> * Other names: Prevenar13;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Mean Fold Increase (MFI; and 95% CI) in vaccine-serotype specific IgG concentrations at 28 days after compared to baseline (before vaccination) | 28 days |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactogenicity | Proportion (% & 95% CI) of participants with local and systemic side effects 24-48 hours after vaccination | 24-48 hours after vaccination |
| Adverse events | Proportion (% & 95% CI) of participants reporting any unexpected adverse effect (AE) during 28 days after vaccination | 28 days |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pneumococcal conjugate vaccine, PCV, Reactogenicity, Immunogenicity, Women childbearing age
|
||
NCT03898063
|
90 DAYS: An Entertainment Education Intervention to Evaluate a Short Film About HIV Status Disclosure
|
This investigation seeks to understand if and how, the 90 Days film can be used as an intervention to address HIV-related stigmas, intimate partner status disclosure and HIV ART medical adherence among Black HIV positive women.
|
An Experimental Investigation of the Effects of an Entertainment Education Short Film on Internalized HIV-related Stigma, Sexual Partner Status Disclosure, and Medical Adherence Intentions Among Black HIV-positive Women in Miami-Dade County
|
HIV/AIDS
|
* Behavioral: 90 DAYS film
* Behavioral: HIV pamphlet on disclosure
|
Inclusion Criteria:~Black women ages 18-50~clinically diagnosed with HIV/AIDS~Speak and comprehend English~Exclusion Criteria:~pregnant women
|
18 Years
|
50 Years
|
Female
|
No
|
Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV Self-stigmatization as Assessed Via Self Stigmatization Questionnaire | self-report measure of the extent to which participants stigmatize themselves for being HIV positive. Quantified in the manuscript using the mean of the self-report scale. Scores range from 1-5 with higher scores indicating higher perceptions of self-stigmatization. | Day 1 post test |
| HIV Disclosure Intentions as Assessed by Disclosure Intentions Scale | Self-report measure of the extent to which participants intend to disclose their HIV status to a partner. Quantified in the manuscript using the mean of the self-report scale. Scores range from 1-5 with higher scores indicating higher intentions of status disclosure. | Day 1 post-test |
| Medical Adherence Intentions as Measured by the Medical Adherence Scale | Self-report measure of participants likeliness to miss doses of their antiretroviral medication over a 30 day period. Quantified in the manuscript using the mean of the self-report scale. Scores range from 1-5 with higher scores indicating increased likeliness to miss doses of antiretroviral medication. | Day 1 post-test |
|
Acquired Immunodeficiency Syndrome, HIV Infections, Blood-Borne Infections, Communicable Diseases, Infections, Sexually Transmitted Diseases, Viral, Sexually Transmitted Diseases, Lentivirus Infections, Retroviridae Infections, RNA Virus Infections, Virus Diseases, Slow Virus Diseases, Genital Diseases, Urogenital Diseases, Immunologic Deficiency Syndromes, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>participants will receive a standard-of-care brochure detailing HIV status disclosure. | Behavioral: HIV pamphlet on disclosure<br>* A standard-of-care brochure given to newly diagnosed HIV patients about the importance of status disclosure<br>|
| Experimental: intervention: 90 DAYS film<br>participants will watch the film, 90 DAYS | Behavioral: 90 DAYS film<br>* the intervention conditions include exposure to a film, 90 DAYS (approx 20 minutes long), an entertainment film detailing a woman's decision to tell her romantic partner that she is HIV-positive.<br>|
|
90 DAYS: An Entertainment Education Intervention to Evaluate a Short Film About HIV Status Disclosure
Study Overview
=================
Brief Summary
-----------------
This investigation seeks to understand if and how, the 90 Days film can be used as an intervention to address HIV-related stigmas, intimate partner status disclosure and HIV ART medical adherence among Black HIV positive women.
Official Title
-----------------
An Experimental Investigation of the Effects of an Entertainment Education Short Film on Internalized HIV-related Stigma, Sexual Partner Status Disclosure, and Medical Adherence Intentions Among Black HIV-positive Women in Miami-Dade County
Conditions
-----------------
HIV/AIDS
Intervention / Treatment
-----------------
* Behavioral: 90 DAYS film
* Behavioral: HIV pamphlet on disclosure
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Black women ages 18-50 clinically diagnosed with HIV/AIDS Speak and comprehend English Exclusion Criteria: pregnant women
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum 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 |
| --- | --- |
| Active Comparator: Control<br>participants will receive a standard-of-care brochure detailing HIV status disclosure. | Behavioral: HIV pamphlet on disclosure<br>* A standard-of-care brochure given to newly diagnosed HIV patients about the importance of status disclosure<br>|
| Experimental: intervention: 90 DAYS film<br>participants will watch the film, 90 DAYS | Behavioral: 90 DAYS film<br>* the intervention conditions include exposure to a film, 90 DAYS (approx 20 minutes long), an entertainment film detailing a woman's decision to tell her romantic partner that she is HIV-positive.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV Self-stigmatization as Assessed Via Self Stigmatization Questionnaire | self-report measure of the extent to which participants stigmatize themselves for being HIV positive. Quantified in the manuscript using the mean of the self-report scale. Scores range from 1-5 with higher scores indicating higher perceptions of self-stigmatization. | Day 1 post test |
| HIV Disclosure Intentions as Assessed by Disclosure Intentions Scale | Self-report measure of the extent to which participants intend to disclose their HIV status to a partner. Quantified in the manuscript using the mean of the self-report scale. Scores range from 1-5 with higher scores indicating higher intentions of status disclosure. | Day 1 post-test |
| Medical Adherence Intentions as Measured by the Medical Adherence Scale | Self-report measure of participants likeliness to miss doses of their antiretroviral medication over a 30 day period. Quantified in the manuscript using the mean of the self-report scale. Scores range from 1-5 with higher scores indicating increased likeliness to miss doses of antiretroviral medication. | Day 1 post-test |
|
|||
NCT04413136
|
Web-Based Treatment for Aphasia
|
This prospective randomized clinical trial implements an innovative broadband web-based treatment program for individuals with chronic aphasia, and evaluates its efficacy. The treatment, Oral Reading for Language in Aphasia (ORLA), has been shown to be efficacious when provided by a speech-language pathologist. The treatment has been computerized and the current version of ORLA uses state-of-the-art virtual therapist technology that allows the individual with aphasia to read aloud, and ultimately speak, sentences at the same time as the words are produced by a perceptive, life-like, animated computer agent, using visible speech. In this clinical trial, ORLA treatment is delivered via the internet and outcomes are compared to a placebo computer treatment.
|
Aphasia is an acquired multi-modality disturbance of language, resulting from focal damage to portions of the brain, typically within the left hemisphere, that are responsible for language. The disorder impairs, in varying degrees, the understanding and expression of oral language, as well as reading and writing. The research literature is replete with information about the treatment of aphasia. Individual studies, together with expert opinion and meta-analyses indicate that those with aphasia benefit from treatments that focus on improving linguistic skills. Furthermore, recent studies have indicated that patients with aphasia, even those beyond the period of spontaneous recovery, benefit from treatment that is provided more frequently. Yet people with aphasia represent an underserved population. Legislation and reimbursement have seriously curtailed the amount of treatment a patient with aphasia may receive. Often patients may be eligible for only a limited number of treatment sessions over a limited period of time. In some cases, patients may not receive any treatment for their communication disorder following their acute hospitalization. Communication treatment costs delivered to patients with chronic aphasia (beyond six months after onset) are seldom reimbursable. Therefore, the establishment and maintenance of programs for effective aphasia remediation are posing new challenges.~There is clearly a need for the development of innovative and effective ways for individuals with aphasia to continue to receive much needed intensive and long-term services that are typically unavailable beyond the acute stage of this disability. Web-based treatment may be a cost-effective way of extending therapy beyond the hospital and clinic, thereby meeting the needs of the growing numbers of individuals with chronic aphasia. This project evaluates the effectiveness of a theoretically-motivated and efficacious treatment that has been integrated with novel computer-based virtual therapy systems and is provided via the internet to individuals with chronic aphasia.~The treatment, Oral Reading for Language in Aphasia (ORLA), is based on a theoretical framework that incorporates two lines of work: the neuropsychological models of reading and observation-execution-matching. Preliminary studies have indicated that this treatment is efficacious when provided by a speech-language pathologist. The treatment has been computerized and the current version of ORLA uses state-of-the-art virtual therapist technology that allows the individual with aphasia to read aloud, and ultimately speak, sentences at the same time as the words are produced by a perceptive, life-like, animated computer agent, using visible speech. In the web-based version, individuals with aphasia work independently on their home computer. The clinician is able to monitor patient use and progress remotely either in real time during the treatment session or after the session at a convenient time.~In this clinical trial, ORLA treatment is delivered via the internet and outcomes are compared to a placebo computer treatment. Thirty-five individuals with chronic aphasia (at least 6 months post onset) are randomized to one of two groups: oral reading (ORLA) treatment group and a control group in which subjects participate in non-language computer activities. Both groups practice for 9 hours per week and treatment continues for a six week period of time. Laptops and high-speed internet connections are provided to the subjects for home practice. Language and communication skills are evaluated pre-treatment, immediately post-treatment, and at 6 weeks after the end of treatment to assess maintenance effects. The primary outcome measure is the Language Quotient of the Western Aphasia Battery.~We hypothesize that implementation of a web-based ORLA treatment for patients with chronic aphasia will result in significant improvements in language, that these improvements are significantly greater than those resulting from placebo computer treatment, and that these improvements will be maintained over time.
|
Web-Based Treatment for Aphasia
|
Aphasia
|
* Behavioral: Web-ORLA
* Behavioral: Control
|
Inclusion Criteria:~men or women with diagnosis of an aphasia subsequent to a left-hemisphere infarct(s) that is confirmed by CT scan or MRI~an Aphasia Quotient score on the Western Aphasia Battery of 20-80.~> 6 months post injury~completed at least an eighth grade education~premorbidly literate in English~sufficient auditory and visual acuity to interact with a laptop~not receiving other speech/language treatment for at least one month prior to or during the study.~Exclusion Criteria:~any other neurological condition (other than cerebral vascular disease) that could potentially affect cognition or speech, such as Parkinson's Disease, Alzheimer's Dementia, traumatic brain injury.~any significant psychiatric history prior to the stroke, such as severe major depression or psychotic disorder requiring hospitalization; subjects with mood disorders who are currently stable on treatment will be considered.~active substance abuse.
|
21 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Aphasia Battery Revised Language Quotient (LQ) | Performance on measures of auditory comprehension, oral expression, reading comprehension and written expression on the WAB-R LQ scale which goes from 0-100. A higher score indicates better performance. | Change from baseline to immediately following 6 weeks of treatment |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Aphasia Battery Revised Language Quotient (LQ) | Performance on measures of auditory comprehension, oral expression, reading comprehension and written expression on the WAB-R LQ scale which goes from 0-100. A higher score indicates better performance. | Change from baseline to 6 weeks after the end of treatment. |
|
Aphasia, Stroke, Rehabilitation, Computer
|
Aphasia, Speech Disorders, Language Disorders, Communication Disorders, Neurobehavioral Manifestations, Neurologic Manifestations, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Web-ORLA<br>Administered 90 minutes a day, six days a week ( i.e. nine hours of computer treatment per week) for a total of six weeks.~The participant is presented with 3-5 word (level 1) or 8-10 word (level 2) sentences, depending upon the severity of the aphasia. Each sentence is chosen by the software program at random from a group of 150 sentences. The participant is instructed to look, listen, and point to words spoken by the virtual therapist, read highlighted words aloud, and then read the sentence aloud, both chorally with the virtual therapist and independently. | Behavioral: Web-ORLA<br> <br> |
| Placebo Comparator: Control<br>Administered 90 minutes a day, six days a week ( i.e. nine hours of computer treatment per week) for a total of six weeks.~A commercially available game, Bejeweled 2, by PopCap. Participants use loaned 13-in laptop computers to access the Bejeweled interface, which displays an 8 X 8 grid of gems of varying shapes and colors. The objective is to match three gems of the same color and shape to score points and advance to more difficult levels. | Behavioral: Control<br> <br> |
|
Web-Based Treatment for Aphasia
Study Overview
=================
Brief Summary
-----------------
This prospective randomized clinical trial implements an innovative broadband web-based treatment program for individuals with chronic aphasia, and evaluates its efficacy. The treatment, Oral Reading for Language in Aphasia (ORLA), has been shown to be efficacious when provided by a speech-language pathologist. The treatment has been computerized and the current version of ORLA uses state-of-the-art virtual therapist technology that allows the individual with aphasia to read aloud, and ultimately speak, sentences at the same time as the words are produced by a perceptive, life-like, animated computer agent, using visible speech. In this clinical trial, ORLA treatment is delivered via the internet and outcomes are compared to a placebo computer treatment.
Detailed Description
-----------------
Aphasia is an acquired multi-modality disturbance of language, resulting from focal damage to portions of the brain, typically within the left hemisphere, that are responsible for language. The disorder impairs, in varying degrees, the understanding and expression of oral language, as well as reading and writing. The research literature is replete with information about the treatment of aphasia. Individual studies, together with expert opinion and meta-analyses indicate that those with aphasia benefit from treatments that focus on improving linguistic skills. Furthermore, recent studies have indicated that patients with aphasia, even those beyond the period of spontaneous recovery, benefit from treatment that is provided more frequently. Yet people with aphasia represent an underserved population. Legislation and reimbursement have seriously curtailed the amount of treatment a patient with aphasia may receive. Often patients may be eligible for only a limited number of treatment sessions over a limited period of time. In some cases, patients may not receive any treatment for their communication disorder following their acute hospitalization. Communication treatment costs delivered to patients with chronic aphasia (beyond six months after onset) are seldom reimbursable. Therefore, the establishment and maintenance of programs for effective aphasia remediation are posing new challenges. There is clearly a need for the development of innovative and effective ways for individuals with aphasia to continue to receive much needed intensive and long-term services that are typically unavailable beyond the acute stage of this disability. Web-based treatment may be a cost-effective way of extending therapy beyond the hospital and clinic, thereby meeting the needs of the growing numbers of individuals with chronic aphasia. This project evaluates the effectiveness of a theoretically-motivated and efficacious treatment that has been integrated with novel computer-based virtual therapy systems and is provided via the internet to individuals with chronic aphasia. The treatment, Oral Reading for Language in Aphasia (ORLA), is based on a theoretical framework that incorporates two lines of work: the neuropsychological models of reading and observation-execution-matching. Preliminary studies have indicated that this treatment is efficacious when provided by a speech-language pathologist. The treatment has been computerized and the current version of ORLA uses state-of-the-art virtual therapist technology that allows the individual with aphasia to read aloud, and ultimately speak, sentences at the same time as the words are produced by a perceptive, life-like, animated computer agent, using visible speech. In the web-based version, individuals with aphasia work independently on their home computer. The clinician is able to monitor patient use and progress remotely either in real time during the treatment session or after the session at a convenient time. In this clinical trial, ORLA treatment is delivered via the internet and outcomes are compared to a placebo computer treatment. Thirty-five individuals with chronic aphasia (at least 6 months post onset) are randomized to one of two groups: oral reading (ORLA) treatment group and a control group in which subjects participate in non-language computer activities. Both groups practice for 9 hours per week and treatment continues for a six week period of time. Laptops and high-speed internet connections are provided to the subjects for home practice. Language and communication skills are evaluated pre-treatment, immediately post-treatment, and at 6 weeks after the end of treatment to assess maintenance effects. The primary outcome measure is the Language Quotient of the Western Aphasia Battery. We hypothesize that implementation of a web-based ORLA treatment for patients with chronic aphasia will result in significant improvements in language, that these improvements are significantly greater than those resulting from placebo computer treatment, and that these improvements will be maintained over time.
Official Title
-----------------
Web-Based Treatment for Aphasia
Conditions
-----------------
Aphasia
Intervention / Treatment
-----------------
* Behavioral: Web-ORLA
* Behavioral: Control
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: men or women with diagnosis of an aphasia subsequent to a left-hemisphere infarct(s) that is confirmed by CT scan or MRI an Aphasia Quotient score on the Western Aphasia Battery of 20-80. > 6 months post injury completed at least an eighth grade education premorbidly literate in English sufficient auditory and visual acuity to interact with a laptop not receiving other speech/language treatment for at least one month prior to or during the study. Exclusion Criteria: any other neurological condition (other than cerebral vascular disease) that could potentially affect cognition or speech, such as Parkinson's Disease, Alzheimer's Dementia, traumatic brain injury. any significant psychiatric history prior to the stroke, such as severe major depression or psychotic disorder requiring hospitalization; subjects with mood disorders who are currently stable on treatment will be considered. active substance abuse.
Ages Eligible for Study
-----------------
Minimum Age: 21 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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Web-ORLA<br>Administered 90 minutes a day, six days a week ( i.e. nine hours of computer treatment per week) for a total of six weeks. The participant is presented with 3-5 word (level 1) or 8-10 word (level 2) sentences, depending upon the severity of the aphasia. Each sentence is chosen by the software program at random from a group of 150 sentences. The participant is instructed to look, listen, and point to words spoken by the virtual therapist, read highlighted words aloud, and then read the sentence aloud, both chorally with the virtual therapist and independently. | Behavioral: Web-ORLA<br> <br> |
| Placebo Comparator: Control<br>Administered 90 minutes a day, six days a week ( i.e. nine hours of computer treatment per week) for a total of six weeks. A commercially available game, Bejeweled 2, by PopCap. Participants use loaned 13-in laptop computers to access the Bejeweled interface, which displays an 8 X 8 grid of gems of varying shapes and colors. The objective is to match three gems of the same color and shape to score points and advance to more difficult levels. | Behavioral: Control<br> <br> |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Aphasia Battery Revised Language Quotient (LQ) | Performance on measures of auditory comprehension, oral expression, reading comprehension and written expression on the WAB-R LQ scale which goes from 0-100. A higher score indicates better performance. | Change from baseline to immediately following 6 weeks of treatment |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Aphasia Battery Revised Language Quotient (LQ) | Performance on measures of auditory comprehension, oral expression, reading comprehension and written expression on the WAB-R LQ scale which goes from 0-100. A higher score indicates better performance. | Change from baseline to 6 weeks after the end of treatment. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aphasia, Stroke, Rehabilitation, Computer
|
NCT04506619
|
Safety and Efficacy Outcomes Following Previously Administered Short-Term Treatment With SHP607 in Extremely Premature Infants
|
The purpose of this study is to evaluate long-term safety and efficacy outcomes following previously administered short-term exposure to SHP607, as compared to a standard neonatal care group.
|
In this long-term follow-up study, participants who enrolled in SHP607-202 (NCT03253263) will be followed from 12 months corrected age (CA) through 60 months CA. Participants will not receive any investigational product in this study.
|
Long-Term Safety and Efficacy Outcomes Following Previously Administered Short-Term Treatment With SHP607 in Extremely Premature Infants
|
Retinopathy of Prematurity (ROP), Intraventricular Hemorrhage, Bronchopulmonary Dysplasia, Chronic Lung Disease of Prematurity
|
* Other: No Intervention
|
Inclusion Criteria:~Participants who were randomized into Study SHP607-202 (NCT03253263). Participants who were randomized, but did not complete Study SHP607-202 (NCT03253263) must be at least 12 months CA.~Written informed consents (and assents, if applicable) must be signed and dated by the participant's parent(s)/legally authorized representative(s) prior to any study-related procedures. The informed consent and any assents for underage parents must be approved by the institutional review board (IRB)/independent ethics committee (IEC).~Exclusion Criteria:~- Participants are excluded from the study if the participant or participant's parent(s)/legally authorized representative(s) is/are unable to comply with the protocol or is/are unlikely to be available for long-term follow-up as determined by the investigator.
|
12 Months
|
24 Months
|
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Emergency Room Visits | Number of emergency room visits associated with a respiratory diagnosis will be reported. | 12 months CA through 60 months CA |
| Number of Hospitalizations | Number of hospitalizations associated with a respiratory diagnosis will be reported. | 12 months CA through 60 months CA |
| Incidence of Signs and Symptoms of Respiratory Disease | Incidence of signs and symptoms of respiratory disease (yes/no) is assessed by recording episodes of wheezing, coughing, and respiratory medication. | 12 months CA through 60 months CA |
| Number of Days of Respiratory Medication Use | Number of days of respiratory medication use (for example, bronchodilators, steroids, leukotriene inhibitors, diuretics) will be reported. | 12 months CA through 60 months CA |
| Total Number of Days on Home Respiratory Technology use | Total number of days on home respiratory technology use (for example, home oxygen, continuous positive airway pressure [CPAP], tracheostomy) will be reported. | 12 months CA through 60 months CA |
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. | 12 months CA through 60 months CA |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth Parameters: Body Weight | Body weight is measured in kilograms (kg) without shoes and with light clothing using a calibrated scale. | At 12, 24, and 60 months CA |
| Growth Parameters: Body Length | Body length is a supine measurement from the top of the head to the sole of the foot with the participant lying on the back with hips and knees extended. | At 12 and 24 months CA |
| Growth Parameters: Height | Height is a measure of participant from head to foot (standing measure). A stadiometer should be utilized for measurement of height. | At 60 months CA |
| Growth parameters: Head circumference | Head circumference or occipital frontal circumference is measured over the occiput and just above the supraorbital ridge, which is the largest circumference of the head. | At 12 and 24 months CA |
| Physical Development as Assessed by Physical Examination | Physical examinations will include a review of the participant's general appearance. | At 12, 24, and 60 months CA |
| Physical Development as Assessed by Neurological Examination for Assessment of Cerebral Palsy | Neurological examination for the diagnosis of cerebral palsy (CP) will be conducted. Neurologic examinations for the diagnosis of CP will be conducted by physicians including assessment of motor function, strength and development, muscle tone, and postural and movement abnormalities. | At 12, 24, and 60 months CA |
| Physical Development as Assessed by Visual Acuity | Visual acuity is a measure of how well a participant sees at different distances. It will be categorized as the following: normal (measurable acuity greater than or equal to [>=] 20/40); below normal (20/200 less than or equal to [<=] measurable acuity <20/40); poor (measurable acuity <=20/200); blind/low vision (only the ability to detect the 2.2 centimeter [cm] wide stripes on the low-vision Teller acuity card and at any location in the visual field). | At 12, 24, and 60 months CA |
| Cognitive Development Assessed by Bayley Scales of Infant and Toddler Development (BSID-III) | The BSID-III will be used to assess cognitive, motor, and language skills, and is applicable to children aged 1-42 months. The BSID-III is an assessment tool designed to measure a young child's skills in the 3 core areas of development: cognitive, language, and motor. There are 5 subscales, the cognitive subscale (Score range: 55-145) stands alone while the 2 language subscales (expressive and receptive) combine to make a total language score (Range: 47-153) and the 2 motor subtests (fine and gross motor) form a combined motor scale (Range: 46-154). A positive value indicates improvement. | At 24 months CA |
| Cognitive Development Quotient Assessed by Kyoto Scale of Psychological Development (KSPD) | KSPD is a alternative scale to the BSID and used to assess cognitive, motor, and language skills at Japan sites only. The KSPD is a validated neurodevelopmental outcome assessment that is standardized for Japanese children and has been evaluated in comparison to BSID in the assessment of developmental characteristics of very low birth weight Japanese infants. The KSPD is designed to measure a young child's skills in three domains of development: Cognitive-Adaptive (non-verbal reasoning or visuospatial perception), Language-Social (interpersonal relationships, socialization, verbal abilities), and Postural-Motor (fine and gross motor functions). The scale consists of 328 items covering a Cognitive-Adaptive area, Language-Social area, and Postural-Motor area. For each of the three areas, a sum score is converted to a Developmental Quotient (dividing the developmental age by the chronological age and then multiplying the quotient by 100). A positive value indicates improvement. | At 24 months CA |
| Cognitive Development Assessed by Wechsler Preschool and Primary Scale of Intelligence (WPPSI) | The WPPSI is a measure of general cognitive development in children that has components of both verbal and non-verbal tasks. It is applicable to preschoolers and young children aged 2 years +6 months to 7 years +7 months, and is a direct assessment of a child's cognitive skills. The standard score For the WPPSI ranges from Below 70 (extremely low) to above 130 (very superior). | At 60 months CA |
| Gross Motor Function Assessed by Gross Motor Function Measure-88 (GMFM-88) | The GMFM-88 item scores is used to calculate a domain-specific percent score for each of the 5 GMFM-88 dimensions, which are the following: Lying and rolling; Sitting; Crawling and kneeling; Standing; Walking, running, and jumping. Each of the 88 items is rated on a 4-point scale: 0=does not initiate; 1=initiates; 2=partially completes; and 3=completes. The GMFM-88 total scores range from 0% (no mobility) to a score of 100%. The test is considered to be appropriate for children whose motor skills are at or below those of a 5-year-old child without any motor disability. The GMFM-88 will be administered at 24 months CA. GMFM-88 Sections D (Standing) and E (Walking, Running and Jumping) only will be administered at 5 years CA. | At 24 and 60 months CA |
| Childhood Behavior Assessed by Vineland Adaptive Behavior Scales (VABS-III) | The VABS-III test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialization, and motor skills. The score ranges from 20 to 140 on which higher scores indicate a higher level of better behavior. | At 24 and 60 months CA |
| Childhood Behavior Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS-V) | The ADHD-RS-V measures the behaviors of children with Attention-Deficit/Hyperactivity Disorder (ADHD). It consists of 18 items designed to reflect current symptomatology of ADHD based on DSM-V criteria. Each item is scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items are grouped into 2 subscales: hyperactivity-impulsivity (even numbered items 2-18) and inattention (inattentiveness) (odd numbered items 1-17). | At 60 months CA |
| Childhood Behavior Assessed by Social Communication Questionnaire (SCQ) | The SCQ is a brief instrument that helps evaluate communication skills and social functioning in children that can be used for screening for autism or autism spectrum disorders (ASD) in the general population. The score ranges from 0 to 39, with a cut off of greater than (>) 15 indicating ASD. | At 60 months CA |
| Health Related Quality of Life (HRQoL) Assessed by the Pediatric Quality of Life Inventory (PedsQL) Scales | HRQoL will be assessed via the validated Pediatric Quality of Life Inventory (PedsQL) Scales appropriate for the child's age of development. The following scales will be used in this study: Infant Scale for ages 13-24 months (45 Items); Toddler Scale for 2-4 years of age (21 Items); Young Child Scale for 5-7 years of age (23 Items). Scores are transformed to a 0 to 100 scale. Higher scores indicate better quality of life. | At 24, 36, 48, and 60 months CA |
| Health Status Measured by the Health Utilities Index 2/3 | The Health Utilities Index (HUI) is a family of generic health profiles and preference-based systems used for measuring health status, reporting HRQoL, and producing utility scores. The HUI 2/3 system contains a number of attributes/domains to classify the level of health status. Each attribute or domain (eg, mobility, cognition, emotion or pain) is rated on a 5-point ordinal scale to indicate the severity level, ranging from 1-5 (higher numbers indicating a more severe level). | At 60 months CA |
| Healthcare Resource Utilization | Healthcare resource utilization is measured by the number of in-patient and outpatient visits, including emergency room visits and visits to specialists. | 12 months CA through 60 months CA |
| Number of Participants With Targeted Medical Events and Fatal Serious Adverse Events (SAEs) | Targeted medical events are intracranial hypertension, any abnormality of glucose metabolism (eg, hypoglycemia, hyperglycemia, and diabetes), tonsillar hypertrophy (based on tonsil examination [part of the physical examination]), and increased cardiac size. A serious adverse event (SAE) is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event. | 12 months CA through 60 months CA |
|
Retinal Diseases, Lung Diseases, Bronchopulmonary Dysplasia, Retinopathy of Prematurity, Premature Birth, Hemorrhage, Pathologic Processes, Obstetric Labor, Premature, Obstetric Labor Complications, Pregnancy Complications, Female Urogenital Diseases and Pregnancy Complications, Urogenital Diseases, Respiratory Tract Diseases, Eye Diseases, Ventilator-Induced Lung Injury, Lung Injury, Infant, Premature, Diseases, Infant, Newborn, Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SHP607 250 mcg/kg/24 hours<br>Participants who received 250 micrograms per kilogram per 24 hours (mcg/kg/24 hours) in the previous study SHP607-202 (NCT03253263) will be followed into this long-term study SHP607-203. | Other: No Intervention<br>* This is a non-interventional study.<br>|
| SHP607 400 mcg/kg/24 hours<br>Participants who received 400 mcg/kg/24 hours in the previous study SHP607-202 (NCT03253263) will be followed into this long-term study SHP607-203. | Other: No Intervention<br>* This is a non-interventional study.<br>|
| Standard Neonatal Care<br>Participants who received standard neonatal care in the previous study SHP607-202 (NCT03253263) will be followed into this long-term study SHP607-203. | Other: No Intervention<br>* This is a non-interventional study.<br>|
|
Safety and Efficacy Outcomes Following Previously Administered Short-Term Treatment With SHP607 in Extremely Premature Infants
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate long-term safety and efficacy outcomes following previously administered short-term exposure to SHP607, as compared to a standard neonatal care group.
Detailed Description
-----------------
In this long-term follow-up study, participants who enrolled in SHP607-202 (NCT03253263) will be followed from 12 months corrected age (CA) through 60 months CA. Participants will not receive any investigational product in this study.
Official Title
-----------------
Long-Term Safety and Efficacy Outcomes Following Previously Administered Short-Term Treatment With SHP607 in Extremely Premature Infants
Conditions
-----------------
Retinopathy of Prematurity (ROP), Intraventricular Hemorrhage, Bronchopulmonary Dysplasia, Chronic Lung Disease of Prematurity
Intervention / Treatment
-----------------
* Other: No Intervention
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants who were randomized into Study SHP607-202 (NCT03253263). Participants who were randomized, but did not complete Study SHP607-202 (NCT03253263) must be at least 12 months CA. Written informed consents (and assents, if applicable) must be signed and dated by the participant's parent(s)/legally authorized representative(s) prior to any study-related procedures. The informed consent and any assents for underage parents must be approved by the institutional review board (IRB)/independent ethics committee (IEC). Exclusion Criteria: - Participants are excluded from the study if the participant or participant's parent(s)/legally authorized representative(s) is/are unable to comply with the protocol or is/are unlikely to be available for long-term follow-up as determined by the investigator.
Ages Eligible for Study
-----------------
Minimum Age: 12 Months
Maximum Age: 24 Months
Sexes Eligible for Study
-----------------
All
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SHP607 250 mcg/kg/24 hours<br>Participants who received 250 micrograms per kilogram per 24 hours (mcg/kg/24 hours) in the previous study SHP607-202 (NCT03253263) will be followed into this long-term study SHP607-203. | Other: No Intervention<br>* This is a non-interventional study.<br>|
| SHP607 400 mcg/kg/24 hours<br>Participants who received 400 mcg/kg/24 hours in the previous study SHP607-202 (NCT03253263) will be followed into this long-term study SHP607-203. | Other: No Intervention<br>* This is a non-interventional study.<br>|
| Standard Neonatal Care<br>Participants who received standard neonatal care in the previous study SHP607-202 (NCT03253263) will be followed into this long-term study SHP607-203. | 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 |
| --- | --- | --- |
| Number of Emergency Room Visits | Number of emergency room visits associated with a respiratory diagnosis will be reported. | 12 months CA through 60 months CA |
| Number of Hospitalizations | Number of hospitalizations associated with a respiratory diagnosis will be reported. | 12 months CA through 60 months CA |
| Incidence of Signs and Symptoms of Respiratory Disease | Incidence of signs and symptoms of respiratory disease (yes/no) is assessed by recording episodes of wheezing, coughing, and respiratory medication. | 12 months CA through 60 months CA |
| Number of Days of Respiratory Medication Use | Number of days of respiratory medication use (for example, bronchodilators, steroids, leukotriene inhibitors, diuretics) will be reported. | 12 months CA through 60 months CA |
| Total Number of Days on Home Respiratory Technology use | Total number of days on home respiratory technology use (for example, home oxygen, continuous positive airway pressure [CPAP], tracheostomy) will be reported. | 12 months CA through 60 months CA |
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. | 12 months CA through 60 months CA |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth Parameters: Body Weight | Body weight is measured in kilograms (kg) without shoes and with light clothing using a calibrated scale. | At 12, 24, and 60 months CA |
| Growth Parameters: Body Length | Body length is a supine measurement from the top of the head to the sole of the foot with the participant lying on the back with hips and knees extended. | At 12 and 24 months CA |
| Growth Parameters: Height | Height is a measure of participant from head to foot (standing measure). A stadiometer should be utilized for measurement of height. | At 60 months CA |
| Growth parameters: Head circumference | Head circumference or occipital frontal circumference is measured over the occiput and just above the supraorbital ridge, which is the largest circumference of the head. | At 12 and 24 months CA |
| Physical Development as Assessed by Physical Examination | Physical examinations will include a review of the participant's general appearance. | At 12, 24, and 60 months CA |
| Physical Development as Assessed by Neurological Examination for Assessment of Cerebral Palsy | Neurological examination for the diagnosis of cerebral palsy (CP) will be conducted. Neurologic examinations for the diagnosis of CP will be conducted by physicians including assessment of motor function, strength and development, muscle tone, and postural and movement abnormalities. | At 12, 24, and 60 months CA |
| Physical Development as Assessed by Visual Acuity | Visual acuity is a measure of how well a participant sees at different distances. It will be categorized as the following: normal (measurable acuity greater than or equal to [>=] 20/40); below normal (20/200 less than or equal to [<=] measurable acuity <20/40); poor (measurable acuity <=20/200); blind/low vision (only the ability to detect the 2.2 centimeter [cm] wide stripes on the low-vision Teller acuity card and at any location in the visual field). | At 12, 24, and 60 months CA |
| Cognitive Development Assessed by Bayley Scales of Infant and Toddler Development (BSID-III) | The BSID-III will be used to assess cognitive, motor, and language skills, and is applicable to children aged 1-42 months. The BSID-III is an assessment tool designed to measure a young child's skills in the 3 core areas of development: cognitive, language, and motor. There are 5 subscales, the cognitive subscale (Score range: 55-145) stands alone while the 2 language subscales (expressive and receptive) combine to make a total language score (Range: 47-153) and the 2 motor subtests (fine and gross motor) form a combined motor scale (Range: 46-154). A positive value indicates improvement. | At 24 months CA |
| Cognitive Development Quotient Assessed by Kyoto Scale of Psychological Development (KSPD) | KSPD is a alternative scale to the BSID and used to assess cognitive, motor, and language skills at Japan sites only. The KSPD is a validated neurodevelopmental outcome assessment that is standardized for Japanese children and has been evaluated in comparison to BSID in the assessment of developmental characteristics of very low birth weight Japanese infants. The KSPD is designed to measure a young child's skills in three domains of development: Cognitive-Adaptive (non-verbal reasoning or visuospatial perception), Language-Social (interpersonal relationships, socialization, verbal abilities), and Postural-Motor (fine and gross motor functions). The scale consists of 328 items covering a Cognitive-Adaptive area, Language-Social area, and Postural-Motor area. For each of the three areas, a sum score is converted to a Developmental Quotient (dividing the developmental age by the chronological age and then multiplying the quotient by 100). A positive value indicates improvement. | At 24 months CA |
| Cognitive Development Assessed by Wechsler Preschool and Primary Scale of Intelligence (WPPSI) | The WPPSI is a measure of general cognitive development in children that has components of both verbal and non-verbal tasks. It is applicable to preschoolers and young children aged 2 years +6 months to 7 years +7 months, and is a direct assessment of a child's cognitive skills. The standard score For the WPPSI ranges from Below 70 (extremely low) to above 130 (very superior). | At 60 months CA |
| Gross Motor Function Assessed by Gross Motor Function Measure-88 (GMFM-88) | The GMFM-88 item scores is used to calculate a domain-specific percent score for each of the 5 GMFM-88 dimensions, which are the following: Lying and rolling; Sitting; Crawling and kneeling; Standing; Walking, running, and jumping. Each of the 88 items is rated on a 4-point scale: 0=does not initiate; 1=initiates; 2=partially completes; and 3=completes. The GMFM-88 total scores range from 0% (no mobility) to a score of 100%. The test is considered to be appropriate for children whose motor skills are at or below those of a 5-year-old child without any motor disability. The GMFM-88 will be administered at 24 months CA. GMFM-88 Sections D (Standing) and E (Walking, Running and Jumping) only will be administered at 5 years CA. | At 24 and 60 months CA |
| Childhood Behavior Assessed by Vineland Adaptive Behavior Scales (VABS-III) | The VABS-III test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialization, and motor skills. The score ranges from 20 to 140 on which higher scores indicate a higher level of better behavior. | At 24 and 60 months CA |
| Childhood Behavior Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS-V) | The ADHD-RS-V measures the behaviors of children with Attention-Deficit/Hyperactivity Disorder (ADHD). It consists of 18 items designed to reflect current symptomatology of ADHD based on DSM-V criteria. Each item is scored from a range of 0 (reflecting no symptoms) to 3 (reflecting severe symptoms) with total scores ranging from 0-54. The 18 items are grouped into 2 subscales: hyperactivity-impulsivity (even numbered items 2-18) and inattention (inattentiveness) (odd numbered items 1-17). | At 60 months CA |
| Childhood Behavior Assessed by Social Communication Questionnaire (SCQ) | The SCQ is a brief instrument that helps evaluate communication skills and social functioning in children that can be used for screening for autism or autism spectrum disorders (ASD) in the general population. The score ranges from 0 to 39, with a cut off of greater than (>) 15 indicating ASD. | At 60 months CA |
| Health Related Quality of Life (HRQoL) Assessed by the Pediatric Quality of Life Inventory (PedsQL) Scales | HRQoL will be assessed via the validated Pediatric Quality of Life Inventory (PedsQL) Scales appropriate for the child's age of development. The following scales will be used in this study: Infant Scale for ages 13-24 months (45 Items); Toddler Scale for 2-4 years of age (21 Items); Young Child Scale for 5-7 years of age (23 Items). Scores are transformed to a 0 to 100 scale. Higher scores indicate better quality of life. | At 24, 36, 48, and 60 months CA |
| Health Status Measured by the Health Utilities Index 2/3 | The Health Utilities Index (HUI) is a family of generic health profiles and preference-based systems used for measuring health status, reporting HRQoL, and producing utility scores. The HUI 2/3 system contains a number of attributes/domains to classify the level of health status. Each attribute or domain (eg, mobility, cognition, emotion or pain) is rated on a 5-point ordinal scale to indicate the severity level, ranging from 1-5 (higher numbers indicating a more severe level). | At 60 months CA |
| Healthcare Resource Utilization | Healthcare resource utilization is measured by the number of in-patient and outpatient visits, including emergency room visits and visits to specialists. | 12 months CA through 60 months CA |
| Number of Participants With Targeted Medical Events and Fatal Serious Adverse Events (SAEs) | Targeted medical events are intracranial hypertension, any abnormality of glucose metabolism (eg, hypoglycemia, hyperglycemia, and diabetes), tonsillar hypertrophy (based on tonsil examination [part of the physical examination]), and increased cardiac size. A serious adverse event (SAE) is defined as an untoward medical occurrence that at any dose meets one or more of the following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event. | 12 months CA through 60 months CA |
|
||
NCT05230368
|
Evaluation of the Safety and the Tolerability of a Combination of Two HIV Inducers in Patients With Undetectable Viral Load
|
The ANRS 171 SYNACTHIV trial is an international multicenter pilot open label phase I trial. This trial will evaluate new procedures in LRA administration in 3 successive cohorts. In case of grade 3 to grade 5 adverse events, the inclusions and treatments will be (but not in a definitive manner) discontinued until the DSMB will conclude that the event was unrelated. Enrolment in cohort 2 then in cohort 3 will start only if no clinical grade 3 to grade 5 adverse event related to the LRAs occurs in the previous cohort.
|
Combination antiretroviral therapy (cART) is potent but not curative. cART requires lifelong adherence. Although multiple reservoirs may exist, the HIV-1 reservoirs containing stably-integrated, transcriptionally-silent but replication-competent proviruses, are recognized to predominate among infected CD4+ T cells. They are therefore a permanent source for virus reactivation and could be responsible for the rebound of plasma viremia observed after cART interruption. Persistence of truly latent (i.e. non-defective) HIV-1 proviruses represents a major obstacle to eradication, as suggested by the failure of cART intensification strategies at clearing the viral reservoirs. Indeed, the levels of HIV-1 reservoirs appear as one of the critical factors influencing the duration of a remission after cART cessation 4. Consequently, a decline of the HIV-1 latent reservoirs size to a level sufficient to permit an efficient control of the infection by the host immune system might allow interruptions in therapy (treatment-free windows). Reactivation of HIV gene expression in latently-infected cells together with an efficient or intensified cART could serve as an adjuvant therapy aimed at eliminating/decreasing the pool of latent viral reservoirs.~The chromatin organization and the epigenetic control of the HIV-1 promoter are key elements involved in transcriptional silencing. The repressive nucleosome nuc-1, located immediately downstream of the transcription start site, is maintained hypoacetylated by histone deacetylases (HDACs) in latent conditions. The use of HDAC inhibitors (HDACis) as latency reversing agents (LRAs) has been well characterized in several latency models and in ex vivo cART-treated HIV-1+ patient cell cultures. Several clinical studies and trials using HDACis were reported [VPA (by Margolis, Siliciano, Lambotte and Routy), SAHA (by Margolis and by Lewin), Panobinostat (by Rasmussen) and romidepsin (by Mellors (ClinicalTrials.gov NCT01933594) and Sogaard)]. The previous studies testing VPA did not show any benefit from this HDACi in reducing the number of latently-infected resting CD4+ T cells. Two clinical trials have demonstrated that administration to cART-treated patients of a single or multiple clinically tolerable dose(s) of SAHA was temporally associated with an increase expression of cell-associated unspliced (CA-US) HIV-1 RNA levels within resting CD4+ T cells in vivo. However, both trials could neither show an increase of residual viremia nor a decrease of the size of HIV-1 reservoirs. Another recent pilot clinical trial with the HDACi Panobinostat has shown a significant increase in CA-US RNA levels but also an increase of plasma HIV genomic RNA level analyzed by a transcription-mediated amplification (TMA) assay as well as a transient decrease in total HIV DNA level. Following cART interruption, this latter trial has shown in some patients a viral load rebound which was delayed compared to the rebound observed in most patients 2-3 weeks after stopping cART. Results from another recent pilot clinical trial including intravenous romidepsin injection, administrated once weekly for 3 weeks while maintaining cART, have shown that 5 out of 6 aviremic patients tested presented viral load levels quantifiable by standard commercial assays. Altogether, these studies are encouraging but question the efficiency of HDACi used alone to reduce the size of the HIV-1 reservoirs or to observe a delay in the viral rebound. The investigators propose some hypotheses in order to explain these partial results and some optimizations to improve therapeutic reactivation strategies:~The level of reactivation obtained in these clinical trials was too weak. Targeting simultaneously different mechanisms of latency should be more efficient when viral eradication is the objective since the combination of different classes of compounds could synergize (i.e. result in a higher reactivation level than the sum of the reactivations produced by each compound individually) to reactivate HIV expression in latently-infected cells.~A precise time schedule for LRA administration may be needed, suggesting that a sequential treatment could improve the effect of administration of two LRAs targeting different latency mechanisms.~HIV-1 latency is a heterogeneous phenomenon. Indeed, the investigators have previously observed in our reactivation studies performed ex vivo a high diversity among the patient cell cultures in terms of pattern of responses to the different LRAs tested. These findings suggest that HIV-1 transcriptional repression results from heterogeneous combinations of molecular mechanisms which vary from one patient to the other. The heterogeneity that the investigators have observed between patients emphasizes the need to evaluate the efficacy of an LRA first ex vivo in cell cultures from a given patient before the administration of this LRA to this given patient in vivo in the context of a clinical trial. Unfortunately, in the vast majority of the previous clinical trials aimed at reactivating HIV-1 from latency, a pre-selection based on ex vivo reactivation assays has not been performed.~Gene expression induction of latent HIV proviruses is stochastic. Indeed, Siliciano's group has shown that after one round of in vitro maximum T-cell activation, some proviruses remain silent but are potentially inducible after additional rounds of activation. In order to maximize the activity of a given LRA, it should thus be administered repeatedly at multiple time points.~Consequently, an optimization of the shock part, first part of the shock and kill strategy, would involve an individualized and combined treatment of LRAs, administered with a precise time schedule and repeatdly at multiple time points. In order to set up such a type of clinical trial, the investigators have investigated in vitro and ex vivo several types of LRA combination. One of them presented several advantages and was approved in human therapy.~Indeed, epigenetically, it is known that DNA methylation and histone deacetylation cooperate to establish and maintain a heterochromatin environment. Indeed, MethylBinding Domain (MBD) proteins bound to methylated DNA in cis-regulators regions can serve as bridges between DNA and chromatin-modifying factors (such as HDACs). In the case of HIV, the HIV-1 promoter has been previously shown to be hypermethylated ex vivo and resistant to reactivation in the latent reservoirs from aviremic HIV-1 infected individuals, as opposed to the hypomethylated 5'LTR of integrated proviruses present in viremic patients. Interestingly, Trejbalova et al. have very recently reported that DNA methylation of the HIV-1 promoter increases progressively during cART treatment. Indeed, these authors have detected low levels of 5' LTR DNA methylation in the resting CD4+ T cells of patients who were cART-treated for up to 3 years. However, after long-term cART, they have observed an accumulation of 5' LTR DNA methylation in the latent reservoir. The DNA methylation status of the HIV-1 promoter could contribute to lock the silent state of the provirus in cooperation with histone repressive posttranslational modifications such as histone deacetylation, thereby making the return of the provirus to an active state more difficult. In this view, demethylating agents could represent promising candidate drugs in combination with HDACis for reducing the pool of latent HIV reservoirs of patients under cART during at least 3 years.~Moreover, it is known that the two epigenetic modifications, DNA methylation and histone deacetylation, are dynamically linked and result in the silencing of genes in cancers. Indeed, several preclinical studies support the view that pharmacologic targeting of both DNMT and HDAC may result in synergistic anticancer activity. Moreover, two clinical trials with the DNA methylation inhibitor Decitabine and the HDACi romidepsin are ongoing in cancer therapy (NCT00037817, NCT00114257). The DNA methylation inhibitor Decitabine approved in human therapy and HDACis present several advantages for HIV-1 purging strategies. Decitabine presents the advantage to cross the blood-brain barrier, to possess an excellent distribution in body fluids, to not induce global T-cell activation. HDACis do not induce global T-cell proliferation or activation, act in a broad spectrum of cell types and potently repress CXCR4 chemokine receptor expression and function. HDACis have also been identified as new P-TEFb-releasing agents. This is undoubtedly another crucial mechanism through which HDACis reactivate HIV expression. Indeed, the switch from promoter proximal pausing to productive elongation is mediated by the viral trans-activator Tat and P-TEFb, an essential cellular elongation transcription factor. In cells, P-TEFb exists in active and inactive forms. Its release from the inactive 7SK small nuclear ribonucleoprotein complex is a critical step for P-TEFb to activate transcription elongation. Thus, importantly, the use of the two drugs might impact other mechanisms (other than histone acetylation and DNA methylation) involved in HIV latency.~1.2 Research hypothesis Recently, our laboratory has evaluated the therapeutic potential of demethylating agents in combination with HDACis in reactivating HIV from latency in vitro and ex vivo. HIV-1 reactivation potential of LRAs was assessed first in vitro in two latently-infected T-cell lines (by quantification of HIV-1 transcription, expression and production) and next ex vivo in CD8+-depleted PBMCs and resting CD4+ T-cell cultures from 58 cART-treated aviremic HIV-1+ patients (by quantification of HIV-1 production). The investigators have shown that the DNA methylation inhibitor 5-aza-2'deoxycytidine (Decitabine), but not 5-azacytidine, induced HIV expression in vitro. The investigators next demonstrated in vitro that a sequential treatment of Decitabine + HDAC is used at clinically tolerable doses synergistically induced HIV expression, highlighting for the first time the importance of a treatment schedule for LRAs combined treatments. Importantly, the investigators have shown the physiological relevance of this synergy and sequential aspect ex vivo. Interestingly, the sequential decitabine + romidepsin combinatory treatment tested induced HIV-1 recovery in a higher manner than the drugs alone in CD8+-depleted PBMCs cultures. In conclusion, the investigators reported for the first time that, in addition to the combinatory aspect, the sequential aspect of LRA administration might be critical for purging strategies aimed at decreasing the reservoir size.~The investigators hypothesize that such sequential combinatory reactivation approaches could lead to a decline in HIV-1 reservoir size to a level sufficient to allow control of the HIV infection by the host immune system and hopefully therapeutic interruptions. However, the first step in order to highlight the benefit of this type of intervention is to evaluate the feasibility, the safety and the tolerability of such sequential combinatory reactivation approaches.~Consequently, based on our ex vivo results and on our proposed optimizations of the shock part, first part of the shock and kill strategy, (involving an individualized and combined treatment of LRAs, administered with a precise time schedule and repeatedly at multiple time points), the investigators propose to set up a phase I trial in HIV-1 sub-type B positive patients under cART for at least 48 months and presenting, to the best knowledge of the clinical PIs, no detectable viral blip for at least 12 months in order to evaluate the feasibility, safety and tolerability of a sequential treatment of Decitabine in combination with romidepsin delivered at multiple time points [one time (cohort 1), two times (cohort 2) or four times (cohort 3)]. As a secondary objective, the investigators will also evaluate the impact on viral reservoirs and HIV gene expression of the combinatory treatment (decitabine + romidepsin).
|
A Pilot Open Label Phase I Trial to Evaluate the Safety and the Tolerability of a Combination of Two HIV-1 Inducers in HIV+ Sub-type B Patients Under cART With Undetectable Viral Load
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HIV-1-infection, Subtype b
|
* Drug: Decitabine cycle 1
* Drug: Romidepsin cycle 1
* Drug: Decitabine cycle 2
* Drug: Romidepsin cycle 2
* Drug: Decitabine cycle 3
* Drug: Romidepsin cycle 3
* Drug: Decitabine cycle 4
* Drug: Romidepsin cycle 4
|
Inclusion Criteria:~Man aged 18-69 years;~Man with documented infection with sub-type B HIV-1;~On cART since more than 48 months before pre- screening and at a stable regimen for at least 2 months 27 before pre-screening and until inclusion;~HIV plasma viral load persistently < the threshold (of the local test used) and undetectable during the 12 months prior to pre-screening and until inclusion, with no blip* allowed (a minimum of 2 VL results are necessary, including the pre-screening value). * blip is defined as 50cp ≤HIV viral load<400 cp mL-1;~CD4+ T-cells count nadir ≥ 200 cells per mm3 documented in the medical file; Transient CD4+ T-cells count < 200 cells per mm3 is allowed for a short period if the value is associated with a single isolated acute infection~CD4+ T-cells count ≥ 500 cells per mm3 for at least 12 months before pre-screening and until inclusion;~EBV viral load < 1000 cp.mL-1, CMV viral load < 10000 cp mL-1;~Complete COVID-19 vaccine scheme (according to national recommendations).~Able and willing to comply with study visits and procedures as per protocol;~Able to understand, sign and date the written voluntary informed consent form at the pre screening visit prior to any protocol-specific procedures.~Regulatory criteria (French regulations):~Free, informed and written consent signed by the person and the investigator (at the latest on the day of pre-screening and before any investigation carried out as part of the trial) (Article L1122-1-1 of the Code of Public Health).~An affiliated person beneficiary of a social security scheme (Article L1121-11 of the Public Health Code) (Aide Médicale d'Etat or AME is not a social security scheme).~A person who agrees to be registered in the national file of persons who lend themselves to biomedical research (article L1121-16 of the Public Health Code).~Regulatory criteria (Belgian regulations):~- Free, informed and written consent signed by the person and the investigator (at the latest on the day of pre-screening and before any investigation carried out as part of the trial) (law of 7 May 2004. article 6)~Exclusion Criteria:~Man who want to father a child or refuse contraception (condoms) while receiving treatment and for 3 months following completion of treatment; Man with a female partner of childbearing potential who refuses to use a highly effective contraceptive method during the same period (Experimental treatment period and for 3 months following completion of experimental treatment).~Clinically significant cardiac disease including QTc-prolongation (QTc value > 450msec);~On PI based regimen or regimen containing NNRTI (except Doravirine which is allowed), Ritonavir or Cobicistat;~Treated with CYP 450 inducer or inhibitor, in particular dexamethasone, carbamazepine, phenytoin, rifabutin, rifapentine and phenobarbital;~Treated with anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation;~Treated with warfarin or coumarin derivative;~History of an AIDS-defining clinical illness (based on CDC classification, appendix A4);~Coinfection with viral hepatitis B;~Coinfection with viral hepatitis C;~Active malignancy that may require chemotherapy or radiation therapy;~Any significant acute medical illness in the 8 weeks prior to pre-screening and until inclusion;~Haematological or biochemical laboratory parameters at pre-screening and screening : Hemoglobin (<LLN), absolute neutrophil count (<LLN), platelets (<LLN), INR (>1.2), Partial Thromboplastin Time (>ULN); grade ≥ 2 for the following parameters: Total serum Creatinine, urea, uric acid, glycemia, total serum bilirubin, Alkaline Phosphatase (ALP) AST-ALT, gammaglutamyl transferase (GGT), lipasemia, LDH, Ionogram: Na, K, Ca, Mg, CRP, albumin, proteins, CPK;~Liver insufficiency (Child Pugh score >5);~Kidney insufficiency (Estimation of glomerular filtration<60mL/mn/1,73m2 ; evaluation with CKDepi formula, according to the 2012 French Haute autorité de santé recommandations);~Participant under guardianship or curatorship or deprived of their liberty by a judicial or administrative decision~Participant potentially inable to follow the protocol requirements (e.g. comprehension of the study requirements, ability to understand and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits).~Participating to another interventional study or still in an exclusion period from another clinical trial (category 1 or 2 study for France);~Planning to participate in a study within 3 months after the end of the present trial.
|
18 Years
|
69 Years
|
Male
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is an international multicenter pilot open label phase I trial. This trial will evaluate new procedures in LRA administration in 3 successive cohorts of 5 patients each receiving 1, 2 and 4 cycles respectively.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Serious Adverse Events (SAE) and severe clinical or biological adverse events (AE) related to the study drugs | Incidence of Serious Adverse Events (SAE) and severe clinical or biological adverse events (AE) related to the study drugs, , according to CTCAE scale, per patient | within 2 weeks after the last injection for each patient |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinical and biological adverse events (AE) of all grades | Incidence, severity and relation to study products of clinical and biological adverse events (AE) of all grades according to CTCAE scale, per cohort | through study completion, an average of 4 years |
| Efficacy of the treatment on the HIV reservoir | Number of total HIV-1 DNA log copies /10e6 cells by an ultrasensitive assay | At pre-screening, before the first dose of each cycle (day 1), 1 hour following each romidepsine administration (day 4, day 11, day 18), at the end of each cycle (day 32), at each follow-up visit (Follow-up days 28, 84, 140, 364) of each cohort. |
| Capacity of latently-infected cells to be reactivated | capacity of latently-infected cells to be reactivated, by the decitabine+romidepsin combination assessed by ex vivo reactivation assay | at screening, at day 32 of each cycle of treatment, at follow-up visit day 140 of each cohort |
| Increase in viral load | Increase in viral load assessed by the classical method performed by the patient's hospital with a threshold at 20 copies/mL or 40 copies/mL | at pre-screening, screening and at day 1 of each cycle (prior decitabin treatment), day 25 and day 32, and at each follow-up visit ((day 28, day 84, day 140, day 364) |
| Increase in viral load | Increase in viral load assessed by an ultrasensitive method with a threshold at 5-10 copies/ml or <2 copies/ml | at pre-screening, screening, day 1 on each cycle (prior decitabin treatment), 1 hour following each romidepsine administration (day 4, day 11, day 18), at the end of each cycle (day 32), and at each follow up visits (day 28, day 84, day 140, day 364) |
| Blood concentration of decitabine and romidepsin after injection | The blood concentration of decitabine and romidepsin after injection. HPLC will be performed on plasma samples collected 5 minutes before the end of drug's administration | day 1, day 4, day 11; day 18 of cycle 1 |
| HIV-1 transcripts measure | The HIV-1 transcripts by an ultrasensitive assay | at screening, day 1, day 4, day 11, day 18, day 32. |
|
Enzyme Inhibitors, Antibiotics, Antineoplastic, Histone Deacetylase Inhibitors, Decitabine, Romidepsin, Antimetabolites, Antineoplastic, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 cycle of treatment (Cohort 1 = 5 patients)<br>decitabine (5mg/m²) at days 1, 2, 3~romidepsin (5mg/m²) at days 4, 11, 18 | Drug: Decitabine cycle 1<br>* Decitabine administration (5mg/m²) at days 1, 2, 3<br>Drug: Romidepsin cycle 1<br>* Romidepsin administration (5mg/m²) at days 4, 11, 18<br>|
| Experimental: 2 cycles of treatment (Cohort 2 = 5 patients)<br>decitabine (5mg/m²) at days 1, 2, 3, 35, 36, 37~romidepsin (5mg/m²) at days 4, 11, 18, 38, 45, 52 | Drug: Decitabine cycle 1<br>* Decitabine administration (5mg/m²) at days 1, 2, 3<br>Drug: Romidepsin cycle 1<br>* Romidepsin administration (5mg/m²) at days 4, 11, 18<br>Drug: Decitabine cycle 2<br>* Decitabine administration (5mg/m²) at days 35, 36, 37<br>Drug: Romidepsin cycle 2<br>* Romidepsin administration (5mg/m²) at days 38, 45, 52<br>|
| Experimental: 4 cycles of treatment (Cohort 3 = 5 patients)<br>decitabine (5mg/m²) at days 1, 2, 3, 35, 36, 37, 70, 71, 72, 105, 106, 107~romidepsin (5mg/m²) at days 4, 11, 18, 38, 45, 52, 73, 80, 87, 108, 115, 122 | Drug: Decitabine cycle 1<br>* Decitabine administration (5mg/m²) at days 1, 2, 3<br>Drug: Romidepsin cycle 1<br>* Romidepsin administration (5mg/m²) at days 4, 11, 18<br>Drug: Decitabine cycle 2<br>* Decitabine administration (5mg/m²) at days 35, 36, 37<br>Drug: Romidepsin cycle 2<br>* Romidepsin administration (5mg/m²) at days 38, 45, 52<br>Drug: Decitabine cycle 3<br>* Decitabine administration (5mg/m²) at days 70, 71, 72<br>Drug: Romidepsin cycle 3<br>* Romidepsin administration (5mg/m²) at days 73, 80, 87<br>Drug: Decitabine cycle 4<br>* Decitabine administration (5mg/m²) at days 105, 106, 107<br>Drug: Romidepsin cycle 4<br>* Romidepsin administration (5mg/m²) at days 108, 115, 122<br>|
|
Evaluation of the Safety and the Tolerability of a Combination of Two HIV Inducers in Patients With Undetectable Viral Load
Study Overview
=================
Brief Summary
-----------------
The ANRS 171 SYNACTHIV trial is an international multicenter pilot open label phase I trial. This trial will evaluate new procedures in LRA administration in 3 successive cohorts. In case of grade 3 to grade 5 adverse events, the inclusions and treatments will be (but not in a definitive manner) discontinued until the DSMB will conclude that the event was unrelated. Enrolment in cohort 2 then in cohort 3 will start only if no clinical grade 3 to grade 5 adverse event related to the LRAs occurs in the previous cohort.
Detailed Description
-----------------
Combination antiretroviral therapy (cART) is potent but not curative. cART requires lifelong adherence. Although multiple reservoirs may exist, the HIV-1 reservoirs containing stably-integrated, transcriptionally-silent but replication-competent proviruses, are recognized to predominate among infected CD4+ T cells. They are therefore a permanent source for virus reactivation and could be responsible for the rebound of plasma viremia observed after cART interruption. Persistence of truly latent (i.e. non-defective) HIV-1 proviruses represents a major obstacle to eradication, as suggested by the failure of cART intensification strategies at clearing the viral reservoirs. Indeed, the levels of HIV-1 reservoirs appear as one of the critical factors influencing the duration of a remission after cART cessation 4. Consequently, a decline of the HIV-1 latent reservoirs size to a level sufficient to permit an efficient control of the infection by the host immune system might allow interruptions in therapy (treatment-free windows). Reactivation of HIV gene expression in latently-infected cells together with an efficient or intensified cART could serve as an adjuvant therapy aimed at eliminating/decreasing the pool of latent viral reservoirs. The chromatin organization and the epigenetic control of the HIV-1 promoter are key elements involved in transcriptional silencing. The repressive nucleosome nuc-1, located immediately downstream of the transcription start site, is maintained hypoacetylated by histone deacetylases (HDACs) in latent conditions. The use of HDAC inhibitors (HDACis) as latency reversing agents (LRAs) has been well characterized in several latency models and in ex vivo cART-treated HIV-1+ patient cell cultures. Several clinical studies and trials using HDACis were reported [VPA (by Margolis, Siliciano, Lambotte and Routy), SAHA (by Margolis and by Lewin), Panobinostat (by Rasmussen) and romidepsin (by Mellors (ClinicalTrials.gov NCT01933594) and Sogaard)]. The previous studies testing VPA did not show any benefit from this HDACi in reducing the number of latently-infected resting CD4+ T cells. Two clinical trials have demonstrated that administration to cART-treated patients of a single or multiple clinically tolerable dose(s) of SAHA was temporally associated with an increase expression of cell-associated unspliced (CA-US) HIV-1 RNA levels within resting CD4+ T cells in vivo. However, both trials could neither show an increase of residual viremia nor a decrease of the size of HIV-1 reservoirs. Another recent pilot clinical trial with the HDACi Panobinostat has shown a significant increase in CA-US RNA levels but also an increase of plasma HIV genomic RNA level analyzed by a transcription-mediated amplification (TMA) assay as well as a transient decrease in total HIV DNA level. Following cART interruption, this latter trial has shown in some patients a viral load rebound which was delayed compared to the rebound observed in most patients 2-3 weeks after stopping cART. Results from another recent pilot clinical trial including intravenous romidepsin injection, administrated once weekly for 3 weeks while maintaining cART, have shown that 5 out of 6 aviremic patients tested presented viral load levels quantifiable by standard commercial assays. Altogether, these studies are encouraging but question the efficiency of HDACi used alone to reduce the size of the HIV-1 reservoirs or to observe a delay in the viral rebound. The investigators propose some hypotheses in order to explain these partial results and some optimizations to improve therapeutic reactivation strategies: The level of reactivation obtained in these clinical trials was too weak. Targeting simultaneously different mechanisms of latency should be more efficient when viral eradication is the objective since the combination of different classes of compounds could synergize (i.e. result in a higher reactivation level than the sum of the reactivations produced by each compound individually) to reactivate HIV expression in latently-infected cells. A precise time schedule for LRA administration may be needed, suggesting that a sequential treatment could improve the effect of administration of two LRAs targeting different latency mechanisms. HIV-1 latency is a heterogeneous phenomenon. Indeed, the investigators have previously observed in our reactivation studies performed ex vivo a high diversity among the patient cell cultures in terms of pattern of responses to the different LRAs tested. These findings suggest that HIV-1 transcriptional repression results from heterogeneous combinations of molecular mechanisms which vary from one patient to the other. The heterogeneity that the investigators have observed between patients emphasizes the need to evaluate the efficacy of an LRA first ex vivo in cell cultures from a given patient before the administration of this LRA to this given patient in vivo in the context of a clinical trial. Unfortunately, in the vast majority of the previous clinical trials aimed at reactivating HIV-1 from latency, a pre-selection based on ex vivo reactivation assays has not been performed. Gene expression induction of latent HIV proviruses is stochastic. Indeed, Siliciano's group has shown that after one round of in vitro maximum T-cell activation, some proviruses remain silent but are potentially inducible after additional rounds of activation. In order to maximize the activity of a given LRA, it should thus be administered repeatedly at multiple time points. Consequently, an optimization of the shock part, first part of the shock and kill strategy, would involve an individualized and combined treatment of LRAs, administered with a precise time schedule and repeatdly at multiple time points. In order to set up such a type of clinical trial, the investigators have investigated in vitro and ex vivo several types of LRA combination. One of them presented several advantages and was approved in human therapy. Indeed, epigenetically, it is known that DNA methylation and histone deacetylation cooperate to establish and maintain a heterochromatin environment. Indeed, MethylBinding Domain (MBD) proteins bound to methylated DNA in cis-regulators regions can serve as bridges between DNA and chromatin-modifying factors (such as HDACs). In the case of HIV, the HIV-1 promoter has been previously shown to be hypermethylated ex vivo and resistant to reactivation in the latent reservoirs from aviremic HIV-1 infected individuals, as opposed to the hypomethylated 5'LTR of integrated proviruses present in viremic patients. Interestingly, Trejbalova et al. have very recently reported that DNA methylation of the HIV-1 promoter increases progressively during cART treatment. Indeed, these authors have detected low levels of 5' LTR DNA methylation in the resting CD4+ T cells of patients who were cART-treated for up to 3 years. However, after long-term cART, they have observed an accumulation of 5' LTR DNA methylation in the latent reservoir. The DNA methylation status of the HIV-1 promoter could contribute to lock the silent state of the provirus in cooperation with histone repressive posttranslational modifications such as histone deacetylation, thereby making the return of the provirus to an active state more difficult. In this view, demethylating agents could represent promising candidate drugs in combination with HDACis for reducing the pool of latent HIV reservoirs of patients under cART during at least 3 years. Moreover, it is known that the two epigenetic modifications, DNA methylation and histone deacetylation, are dynamically linked and result in the silencing of genes in cancers. Indeed, several preclinical studies support the view that pharmacologic targeting of both DNMT and HDAC may result in synergistic anticancer activity. Moreover, two clinical trials with the DNA methylation inhibitor Decitabine and the HDACi romidepsin are ongoing in cancer therapy (NCT00037817, NCT00114257). The DNA methylation inhibitor Decitabine approved in human therapy and HDACis present several advantages for HIV-1 purging strategies. Decitabine presents the advantage to cross the blood-brain barrier, to possess an excellent distribution in body fluids, to not induce global T-cell activation. HDACis do not induce global T-cell proliferation or activation, act in a broad spectrum of cell types and potently repress CXCR4 chemokine receptor expression and function. HDACis have also been identified as new P-TEFb-releasing agents. This is undoubtedly another crucial mechanism through which HDACis reactivate HIV expression. Indeed, the switch from promoter proximal pausing to productive elongation is mediated by the viral trans-activator Tat and P-TEFb, an essential cellular elongation transcription factor. In cells, P-TEFb exists in active and inactive forms. Its release from the inactive 7SK small nuclear ribonucleoprotein complex is a critical step for P-TEFb to activate transcription elongation. Thus, importantly, the use of the two drugs might impact other mechanisms (other than histone acetylation and DNA methylation) involved in HIV latency. 1.2 Research hypothesis Recently, our laboratory has evaluated the therapeutic potential of demethylating agents in combination with HDACis in reactivating HIV from latency in vitro and ex vivo. HIV-1 reactivation potential of LRAs was assessed first in vitro in two latently-infected T-cell lines (by quantification of HIV-1 transcription, expression and production) and next ex vivo in CD8+-depleted PBMCs and resting CD4+ T-cell cultures from 58 cART-treated aviremic HIV-1+ patients (by quantification of HIV-1 production). The investigators have shown that the DNA methylation inhibitor 5-aza-2'deoxycytidine (Decitabine), but not 5-azacytidine, induced HIV expression in vitro. The investigators next demonstrated in vitro that a sequential treatment of Decitabine + HDAC is used at clinically tolerable doses synergistically induced HIV expression, highlighting for the first time the importance of a treatment schedule for LRAs combined treatments. Importantly, the investigators have shown the physiological relevance of this synergy and sequential aspect ex vivo. Interestingly, the sequential decitabine + romidepsin combinatory treatment tested induced HIV-1 recovery in a higher manner than the drugs alone in CD8+-depleted PBMCs cultures. In conclusion, the investigators reported for the first time that, in addition to the combinatory aspect, the sequential aspect of LRA administration might be critical for purging strategies aimed at decreasing the reservoir size. The investigators hypothesize that such sequential combinatory reactivation approaches could lead to a decline in HIV-1 reservoir size to a level sufficient to allow control of the HIV infection by the host immune system and hopefully therapeutic interruptions. However, the first step in order to highlight the benefit of this type of intervention is to evaluate the feasibility, the safety and the tolerability of such sequential combinatory reactivation approaches. Consequently, based on our ex vivo results and on our proposed optimizations of the shock part, first part of the shock and kill strategy, (involving an individualized and combined treatment of LRAs, administered with a precise time schedule and repeatedly at multiple time points), the investigators propose to set up a phase I trial in HIV-1 sub-type B positive patients under cART for at least 48 months and presenting, to the best knowledge of the clinical PIs, no detectable viral blip for at least 12 months in order to evaluate the feasibility, safety and tolerability of a sequential treatment of Decitabine in combination with romidepsin delivered at multiple time points [one time (cohort 1), two times (cohort 2) or four times (cohort 3)]. As a secondary objective, the investigators will also evaluate the impact on viral reservoirs and HIV gene expression of the combinatory treatment (decitabine + romidepsin).
Official Title
-----------------
A Pilot Open Label Phase I Trial to Evaluate the Safety and the Tolerability of a Combination of Two HIV-1 Inducers in HIV+ Sub-type B Patients Under cART With Undetectable Viral Load
Conditions
-----------------
HIV-1-infection, Subtype b
Intervention / Treatment
-----------------
* Drug: Decitabine cycle 1
* Drug: Romidepsin cycle 1
* Drug: Decitabine cycle 2
* Drug: Romidepsin cycle 2
* Drug: Decitabine cycle 3
* Drug: Romidepsin cycle 3
* Drug: Decitabine cycle 4
* Drug: Romidepsin cycle 4
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Man aged 18-69 years; Man with documented infection with sub-type B HIV-1; On cART since more than 48 months before pre- screening and at a stable regimen for at least 2 months 27 before pre-screening and until inclusion; HIV plasma viral load persistently < the threshold (of the local test used) and undetectable during the 12 months prior to pre-screening and until inclusion, with no blip* allowed (a minimum of 2 VL results are necessary, including the pre-screening value). * blip is defined as 50cp ≤HIV viral load<400 cp mL-1; CD4+ T-cells count nadir ≥ 200 cells per mm3 documented in the medical file; Transient CD4+ T-cells count < 200 cells per mm3 is allowed for a short period if the value is associated with a single isolated acute infection CD4+ T-cells count ≥ 500 cells per mm3 for at least 12 months before pre-screening and until inclusion; EBV viral load < 1000 cp.mL-1, CMV viral load < 10000 cp mL-1; Complete COVID-19 vaccine scheme (according to national recommendations). Able and willing to comply with study visits and procedures as per protocol; Able to understand, sign and date the written voluntary informed consent form at the pre screening visit prior to any protocol-specific procedures. Regulatory criteria (French regulations): Free, informed and written consent signed by the person and the investigator (at the latest on the day of pre-screening and before any investigation carried out as part of the trial) (Article L1122-1-1 of the Code of Public Health). An affiliated person beneficiary of a social security scheme (Article L1121-11 of the Public Health Code) (Aide Médicale d'Etat or AME is not a social security scheme). A person who agrees to be registered in the national file of persons who lend themselves to biomedical research (article L1121-16 of the Public Health Code). Regulatory criteria (Belgian regulations): - Free, informed and written consent signed by the person and the investigator (at the latest on the day of pre-screening and before any investigation carried out as part of the trial) (law of 7 May 2004. article 6) Exclusion Criteria: Man who want to father a child or refuse contraception (condoms) while receiving treatment and for 3 months following completion of treatment; Man with a female partner of childbearing potential who refuses to use a highly effective contraceptive method during the same period (Experimental treatment period and for 3 months following completion of experimental treatment). Clinically significant cardiac disease including QTc-prolongation (QTc value > 450msec); On PI based regimen or regimen containing NNRTI (except Doravirine which is allowed), Ritonavir or Cobicistat; Treated with CYP 450 inducer or inhibitor, in particular dexamethasone, carbamazepine, phenytoin, rifabutin, rifapentine and phenobarbital; Treated with anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation; Treated with warfarin or coumarin derivative; History of an AIDS-defining clinical illness (based on CDC classification, appendix A4); Coinfection with viral hepatitis B; Coinfection with viral hepatitis C; Active malignancy that may require chemotherapy or radiation therapy; Any significant acute medical illness in the 8 weeks prior to pre-screening and until inclusion; Haematological or biochemical laboratory parameters at pre-screening and screening : Hemoglobin (<LLN), absolute neutrophil count (<LLN), platelets (<LLN), INR (>1.2), Partial Thromboplastin Time (>ULN); grade ≥ 2 for the following parameters: Total serum Creatinine, urea, uric acid, glycemia, total serum bilirubin, Alkaline Phosphatase (ALP) AST-ALT, gammaglutamyl transferase (GGT), lipasemia, LDH, Ionogram: Na, K, Ca, Mg, CRP, albumin, proteins, CPK; Liver insufficiency (Child Pugh score >5); Kidney insufficiency (Estimation of glomerular filtration<60mL/mn/1,73m2 ; evaluation with CKDepi formula, according to the 2012 French Haute autorité de santé recommandations); Participant under guardianship or curatorship or deprived of their liberty by a judicial or administrative decision Participant potentially inable to follow the protocol requirements (e.g. comprehension of the study requirements, ability to understand and comply with procedures for collection of safety data, expressed availability for the required study period, and ability and willingness to attend scheduled visits). Participating to another interventional study or still in an exclusion period from another clinical trial (category 1 or 2 study for France); Planning to participate in a study within 3 months after the end of the present trial.
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 69 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
No
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is an international multicenter pilot open label phase I trial. This trial will evaluate new procedures in LRA administration in 3 successive cohorts of 5 patients each receiving 1, 2 and 4 cycles respectively.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 cycle of treatment (Cohort 1 = 5 patients)<br>decitabine (5mg/m²) at days 1, 2, 3 romidepsin (5mg/m²) at days 4, 11, 18 | Drug: Decitabine cycle 1<br>* Decitabine administration (5mg/m²) at days 1, 2, 3<br>Drug: Romidepsin cycle 1<br>* Romidepsin administration (5mg/m²) at days 4, 11, 18<br>|
| Experimental: 2 cycles of treatment (Cohort 2 = 5 patients)<br>decitabine (5mg/m²) at days 1, 2, 3, 35, 36, 37 romidepsin (5mg/m²) at days 4, 11, 18, 38, 45, 52 | Drug: Decitabine cycle 1<br>* Decitabine administration (5mg/m²) at days 1, 2, 3<br>Drug: Romidepsin cycle 1<br>* Romidepsin administration (5mg/m²) at days 4, 11, 18<br>Drug: Decitabine cycle 2<br>* Decitabine administration (5mg/m²) at days 35, 36, 37<br>Drug: Romidepsin cycle 2<br>* Romidepsin administration (5mg/m²) at days 38, 45, 52<br>|
| Experimental: 4 cycles of treatment (Cohort 3 = 5 patients)<br>decitabine (5mg/m²) at days 1, 2, 3, 35, 36, 37, 70, 71, 72, 105, 106, 107 romidepsin (5mg/m²) at days 4, 11, 18, 38, 45, 52, 73, 80, 87, 108, 115, 122 | Drug: Decitabine cycle 1<br>* Decitabine administration (5mg/m²) at days 1, 2, 3<br>Drug: Romidepsin cycle 1<br>* Romidepsin administration (5mg/m²) at days 4, 11, 18<br>Drug: Decitabine cycle 2<br>* Decitabine administration (5mg/m²) at days 35, 36, 37<br>Drug: Romidepsin cycle 2<br>* Romidepsin administration (5mg/m²) at days 38, 45, 52<br>Drug: Decitabine cycle 3<br>* Decitabine administration (5mg/m²) at days 70, 71, 72<br>Drug: Romidepsin cycle 3<br>* Romidepsin administration (5mg/m²) at days 73, 80, 87<br>Drug: Decitabine cycle 4<br>* Decitabine administration (5mg/m²) at days 105, 106, 107<br>Drug: Romidepsin cycle 4<br>* Romidepsin administration (5mg/m²) at days 108, 115, 122<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Serious Adverse Events (SAE) and severe clinical or biological adverse events (AE) related to the study drugs | Incidence of Serious Adverse Events (SAE) and severe clinical or biological adverse events (AE) related to the study drugs, , according to CTCAE scale, per patient | within 2 weeks after the last injection for each patient |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinical and biological adverse events (AE) of all grades | Incidence, severity and relation to study products of clinical and biological adverse events (AE) of all grades according to CTCAE scale, per cohort | through study completion, an average of 4 years |
| Efficacy of the treatment on the HIV reservoir | Number of total HIV-1 DNA log copies /10e6 cells by an ultrasensitive assay | At pre-screening, before the first dose of each cycle (day 1), 1 hour following each romidepsine administration (day 4, day 11, day 18), at the end of each cycle (day 32), at each follow-up visit (Follow-up days 28, 84, 140, 364) of each cohort. |
| Capacity of latently-infected cells to be reactivated | capacity of latently-infected cells to be reactivated, by the decitabine+romidepsin combination assessed by ex vivo reactivation assay | at screening, at day 32 of each cycle of treatment, at follow-up visit day 140 of each cohort |
| Increase in viral load | Increase in viral load assessed by the classical method performed by the patient's hospital with a threshold at 20 copies/mL or 40 copies/mL | at pre-screening, screening and at day 1 of each cycle (prior decitabin treatment), day 25 and day 32, and at each follow-up visit ((day 28, day 84, day 140, day 364) |
| Increase in viral load | Increase in viral load assessed by an ultrasensitive method with a threshold at 5-10 copies/ml or <2 copies/ml | at pre-screening, screening, day 1 on each cycle (prior decitabin treatment), 1 hour following each romidepsine administration (day 4, day 11, day 18), at the end of each cycle (day 32), and at each follow up visits (day 28, day 84, day 140, day 364) |
| Blood concentration of decitabine and romidepsin after injection | The blood concentration of decitabine and romidepsin after injection. HPLC will be performed on plasma samples collected 5 minutes before the end of drug's administration | day 1, day 4, day 11; day 18 of cycle 1 |
| HIV-1 transcripts measure | The HIV-1 transcripts by an ultrasensitive assay | at screening, day 1, day 4, day 11, day 18, day 32. |
|
|
NCT00690118
|
Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis
|
Primary objective:~Efficacy of pioglitazone (45 mg/day) as add-on therapy to standard therapy with riluzole in patients with ALS compared to placebo in terms of survival (mortality defined exclusively as death).~This is a prospective, multicentre, randomised, stratified, parallel-group, double-blind trial comparing placebo with 45 mg pioglitazone as add-on therapy to 100 mg riluzole in ALS in 220 enrolled patients. For entry, the El Escorial Criteria for diagnosis will be used. The duration of treatment will be 18 months. The primary endpoint will be subjected to a confirmatory analyses. Secondary variables will be incidence of tracheotomy or non-invasive ventilation, ALS Functional Rating Scale, Quality of life and safety variables.
|
Efficacy, Safety and Tolerability Study of 45 mg Pioglitazone in Patients With Amyotrophic Lateral Sclerosis (ALS) Receiving Standard Therapy (Riluzole)
|
Amyotrophic Lateral Sclerosis
|
* Drug: pioglitazone
* Drug: placebo
|
Inclusion Criteria:~possible, probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria~disease duration more than 6 months and less than 3 years~best-sitting FVC between 50% and 95% of predicted normal~continuously treated with 100 mg riluzole daily, for at least one month~onset of progression weakness within 36 months prior to study~women of childbearing age be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test~capable of thoroughly understanding all information given and giving full informed consent according to GCP~Exclusion Criteria:~previous participation in another clinical study within the preceding three months~tracheotomy or assisted ventilation of any type during the preceding three months~gastrostomy~any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS~presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment~confirmed hepatic insufficiency or abnormal liver function (ASAT and/or ALAT more than 1.5 upper limit of normal)~renal insufficiency (serum creatinine more than 2.26 mg/dl)~evidence of major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms~known hypersensitivity to any component of the study drugs~likely to be not cooperative or comply with the trial requirements (as assessed by the investigator), or unable to be reached in the case of an emergency~other antidiabetics~heart failure or heart failure in the patients history (NYHA I to IV)~history of macular oedema~treatment with thiazolidinediones within 3 months prior to screening~known or suspected history of alcohol and/or drug abuse~treatment with gemfibrozil within 3 months prior to screening
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival in patients with ALS treated with pioglitazone compared to placebo | | 18 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of tracheotomy or non-invasive ventilation | | 18 month |
|
amyotrophic lateral sclerosis, survival time, ALS functioning Rating Scale, quality of life, non-invasive ventilation, clinical tolerability, survival
|
Pioglitazone, Hypoglycemic Agents, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: pioglitazone<br>* 45 mg/day, 18 months<br>* Other names: Actos;|
| Placebo Comparator: 2<br> | Drug: placebo<br>* once daily, 18 months<br>|
|
Study of Pioglitazone in Patients With Amyotrophic Lateral Sclerosis
Study Overview
=================
Brief Summary
-----------------
Primary objective: Efficacy of pioglitazone (45 mg/day) as add-on therapy to standard therapy with riluzole in patients with ALS compared to placebo in terms of survival (mortality defined exclusively as death). This is a prospective, multicentre, randomised, stratified, parallel-group, double-blind trial comparing placebo with 45 mg pioglitazone as add-on therapy to 100 mg riluzole in ALS in 220 enrolled patients. For entry, the El Escorial Criteria for diagnosis will be used. The duration of treatment will be 18 months. The primary endpoint will be subjected to a confirmatory analyses. Secondary variables will be incidence of tracheotomy or non-invasive ventilation, ALS Functional Rating Scale, Quality of life and safety variables.
Official Title
-----------------
Efficacy, Safety and Tolerability Study of 45 mg Pioglitazone in Patients With Amyotrophic Lateral Sclerosis (ALS) Receiving Standard Therapy (Riluzole)
Conditions
-----------------
Amyotrophic Lateral Sclerosis
Intervention / Treatment
-----------------
* Drug: pioglitazone
* Drug: placebo
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: possible, probable (clinically or laboratory) or definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria disease duration more than 6 months and less than 3 years best-sitting FVC between 50% and 95% of predicted normal continuously treated with 100 mg riluzole daily, for at least one month onset of progression weakness within 36 months prior to study women of childbearing age be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test capable of thoroughly understanding all information given and giving full informed consent according to GCP Exclusion Criteria: previous participation in another clinical study within the preceding three months tracheotomy or assisted ventilation of any type during the preceding three months gastrostomy any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment confirmed hepatic insufficiency or abnormal liver function (ASAT and/or ALAT more than 1.5 upper limit of normal) renal insufficiency (serum creatinine more than 2.26 mg/dl) evidence of major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms known hypersensitivity to any component of the study drugs likely to be not cooperative or comply with the trial requirements (as assessed by the investigator), or unable to be reached in the case of an emergency other antidiabetics heart failure or heart failure in the patients history (NYHA I to IV) history of macular oedema treatment with thiazolidinediones within 3 months prior to screening known or suspected history of alcohol and/or drug abuse treatment with gemfibrozil within 3 months prior to screening
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: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: pioglitazone<br>* 45 mg/day, 18 months<br>* Other names: Actos;|
| Placebo Comparator: 2<br> | Drug: placebo<br>* once daily, 18 months<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival in patients with ALS treated with pioglitazone compared to placebo | | 18 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of tracheotomy or non-invasive ventilation | | 18 month |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
amyotrophic lateral sclerosis, survival time, ALS functioning Rating Scale, quality of life, non-invasive ventilation, clinical tolerability, survival
|
|
NCT01226732
|
A Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors
|
The investigators propose this Phase I trial of the combination of AUY922 and capecitabine to determine the maximum tolerated dose (MTD) in patients with advanced solid tumors. This combination treatment has potential applicability in tumor types where capecitabine or fluorouracil is a treatment option, including colorectal and breast cancer.
|
A Phase I Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors
|
Metastatic or Unresectable Solid Tumor Malignancy
|
* Drug: Capecitabine
* Drug: Hsp90 Inhibitor AUY 922
|
Inclusion Criteria:~Histologically confirmed metastatic or unresectable solid tumor malignancy that is incurable and for which capecitabine is clinically appropriate.~Patient must be ≥4 weeks from administration of last dose of cancer therapy (including radiation therapy, biologic therapy, hormonal therapy or chemotherapy). Patients who received a small molecule targeted therapy as part of their first line treatment regimen must be ≥4 weeks or ≥5 half lives from administration of last dose whichever is shorter. The patient must have recovered from or come to a new chronic stable baseline from all treatment-related toxicities.~Eastern Collaborative Oncology Group (ECOG) performance status 0 to 1 (see Appendix A).~Life expectancy of ≥3 months.~At least one unidimensional measurable lesion definable by MRI or CT scan. Disease must be measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (see Section 9).~Normal bone marrow function defined as:~Absolute neutrophil count (ANC) ≥1500/μL~Hemoglobin (Hgb) ≥9 g/dL~Platelets ≥100,000/μL~Adequate hepatic function defined as:~AST or ALT and alkaline phosphatase (ALP) must be ≤3 x ULN, or ≤5 x ULN in patients with liver metastases~Total bilirubin ≤1.5 x the institutional ULN~Renal function defined as:~• Serum creatinine ≤1.5 x ULN or 24-hour creatinine clearance ≥40 mL/min~Normal electrolytes defined as:~Phosphorous ≥ LLN~Magnesium ≥ LLN~Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential must use effective birth control measures during treatment and during the 6 months following completion of study treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.~Must be ≥18 years of age.~Patients must be accessible for treatment and follow-up.~Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.~Exclusion Criteria:~Untreated CNS metastases. Patients with treated CNS metastases may be enrolled, provided the patient is asymptomatic, and the patient does not require antiepileptic drugs or steroids as treatment for the CNS metastases.~Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).~Impaired cardiac function with any one of the following:~History (or family history) of long QT syndrome~Mean QTc ≥450 msec on baseline ECG~History of clinically manifested ischemic heart disease (i.e. myocardial infarction and/or unstable angina) ≤6 months prior to study start~History of heart failure or left ventricular (LV) dysfunction (LVEF ≤45%) by MUGA or ECHO~Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB). ST segment elevation or depression > 1mm, or 2nd (Mobitz II), or 3rd degree AV block.~History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes~Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)~Clinically significant resting bradycardia (< 50 beats per minute)~Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be switched to an alternative drug or discontinued prior to commencing AUY922 (see Appendix D).~Obligate use of a cardiac pacemaker~Impairment of gastrointestinal function or gastrointestinal disease that in the opinion of the Investigator may significantly alter the absorption of study drugs (e.g., Crohn's disease, ulcerative disease, uncontrolled vomiting, diarrhea, or malabsorption syndrome).~Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection.~Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.~Women who are pregnant (positive pregnancy test) or lactating.~Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study, and the inability to comply with study and/or follow-up procedures.
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Determination | To determine the maximum tolerated dose (MTD) of AUY922 plus capecitabine in patients with advanced solid tumors. | 18 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Related Toxicities | To evaluate the drug related toxicities associated with different doses of the drugs used in this regimen. | 18 months |
| Preliminary Efficacy Assessment: Response Rate (RR) | Response Rate (RR) is defined as the total number of patients with Complete Response (CR) or Partial Response (PR) as defined in RECIST v2. CR is defined as the dissappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor markers. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | 18 months |
|
Solid tumor, Capecitabine, Hsp90 inhibitor AUY922
|
Antimetabolites, Antineoplastic, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Capecitabine
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1<br>Hsp90 Inhibitor AUY922: 22mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
| Experimental: Dose Level 2<br>Hsp90 Inhibitor AUY922: 28mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
| Experimental: Dose Level 3<br>Hsp90 Inhibitor AUY922: 40mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
| Experimental: Dose Level 4<br>Hsp90 Inhibitor AUY922: 55mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
| Experimental: Dose Level 5<br>Hsp90 Inhibitor AUY922: 70mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
| Experimental: Dose Level 6<br>Hsp90 Inhibitor AUY922: 70mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1250mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
|
A Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors
Study Overview
=================
Brief Summary
-----------------
The investigators propose this Phase I trial of the combination of AUY922 and capecitabine to determine the maximum tolerated dose (MTD) in patients with advanced solid tumors. This combination treatment has potential applicability in tumor types where capecitabine or fluorouracil is a treatment option, including colorectal and breast cancer.
Official Title
-----------------
A Phase I Study of the Hsp90 Inhibitor AUY922 Plus Capecitabine for the Treatment of Patients With Advanced Solid Tumors
Conditions
-----------------
Metastatic or Unresectable Solid Tumor Malignancy
Intervention / Treatment
-----------------
* Drug: Capecitabine
* Drug: Hsp90 Inhibitor AUY 922
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed metastatic or unresectable solid tumor malignancy that is incurable and for which capecitabine is clinically appropriate. Patient must be ≥4 weeks from administration of last dose of cancer therapy (including radiation therapy, biologic therapy, hormonal therapy or chemotherapy). Patients who received a small molecule targeted therapy as part of their first line treatment regimen must be ≥4 weeks or ≥5 half lives from administration of last dose whichever is shorter. The patient must have recovered from or come to a new chronic stable baseline from all treatment-related toxicities. Eastern Collaborative Oncology Group (ECOG) performance status 0 to 1 (see Appendix A). Life expectancy of ≥3 months. At least one unidimensional measurable lesion definable by MRI or CT scan. Disease must be measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (see Section 9). Normal bone marrow function defined as: Absolute neutrophil count (ANC) ≥1500/μL Hemoglobin (Hgb) ≥9 g/dL Platelets ≥100,000/μL Adequate hepatic function defined as: AST or ALT and alkaline phosphatase (ALP) must be ≤3 x ULN, or ≤5 x ULN in patients with liver metastases Total bilirubin ≤1.5 x the institutional ULN Renal function defined as: • Serum creatinine ≤1.5 x ULN or 24-hour creatinine clearance ≥40 mL/min Normal electrolytes defined as: Phosphorous ≥ LLN Magnesium ≥ LLN Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential must use effective birth control measures during treatment and during the 6 months following completion of study treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. Must be ≥18 years of age. Patients must be accessible for treatment and follow-up. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry. Exclusion Criteria: Untreated CNS metastases. Patients with treated CNS metastases may be enrolled, provided the patient is asymptomatic, and the patient does not require antiepileptic drugs or steroids as treatment for the CNS metastases. Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted). Impaired cardiac function with any one of the following: History (or family history) of long QT syndrome Mean QTc ≥450 msec on baseline ECG History of clinically manifested ischemic heart disease (i.e. myocardial infarction and/or unstable angina) ≤6 months prior to study start History of heart failure or left ventricular (LV) dysfunction (LVEF ≤45%) by MUGA or ECHO Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB). ST segment elevation or depression > 1mm, or 2nd (Mobitz II), or 3rd degree AV block. History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) Clinically significant resting bradycardia (< 50 beats per minute) Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be switched to an alternative drug or discontinued prior to commencing AUY922 (see Appendix D). Obligate use of a cardiac pacemaker Impairment of gastrointestinal function or gastrointestinal disease that in the opinion of the Investigator may significantly alter the absorption of study drugs (e.g., Crohn's disease, ulcerative disease, uncontrolled vomiting, diarrhea, or malabsorption syndrome). Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus, or acute or chronic hepatitis B infection. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. Women who are pregnant (positive pregnancy test) or lactating. Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study, and the inability to comply with study and/or follow-up 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: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1<br>Hsp90 Inhibitor AUY922: 22mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
| Experimental: Dose Level 2<br>Hsp90 Inhibitor AUY922: 28mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
| Experimental: Dose Level 3<br>Hsp90 Inhibitor AUY922: 40mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
| Experimental: Dose Level 4<br>Hsp90 Inhibitor AUY922: 55mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
| Experimental: Dose Level 5<br>Hsp90 Inhibitor AUY922: 70mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1000mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
| Experimental: Dose Level 6<br>Hsp90 Inhibitor AUY922: 70mg/m2 IV days 1, 8, and 15 of 21-day cycles Capecitabine: 1250mg/m2 PO BID d 1-14 of 21-day cycles | Drug: Capecitabine<br>* Taken orally twice daily on Days 1 through 14 of 21 day cycle.<br>* Other names: Xeloda;Drug: Hsp90 Inhibitor AUY 922<br>* IV infusion over 60 minutes on Days 1, 8, and 15 of each 21 day cycle<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Determination | To determine the maximum tolerated dose (MTD) of AUY922 plus capecitabine in patients with advanced solid tumors. | 18 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Related Toxicities | To evaluate the drug related toxicities associated with different doses of the drugs used in this regimen. | 18 months |
| Preliminary Efficacy Assessment: Response Rate (RR) | Response Rate (RR) is defined as the total number of patients with Complete Response (CR) or Partial Response (PR) as defined in RECIST v2. CR is defined as the dissappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor markers. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. | 18 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Solid tumor, Capecitabine, Hsp90 inhibitor AUY922
|
|
NCT01361971
|
Hyperbaric Oxygen Treatment Ameliorates Insulin Resistance
|
Obesity is an epidemic in Western society and is the biggest risk factor for insulin resistance and type 2 diabetes. The investigators have preliminary evidence showing that hyperbaric oxygen therapy rapidly increases insulin sensitivity in humans. This requires confirmation in a larger population, and with this study the investigators will also test for mechanisms how this occurs. The investigators suspect that modulation of hypoxia and stress response proteins following changes in tissue oxygenation may contribute to these improvements. This study has the potential to yield new and important insights into the insulin resistance in obesity.
|
Hyperbaric Oxygen Treatment Ameliorates Insulin Resistance
|
Obesity, Type 2 Diabetes
|
* Procedure: Hyperbaric Oxygen Treatment
|
Inclusion Criteria:~Obese men with and without type 2 diabetes aged 45-70~Lean men without type 2 diabetes aged 45-70~Exclusion Criteria:~smokers~claustrophobic~sleep apnoea~blood donor~exercise more than 2 times per week~under certain medications eg: bleomycin,corticosteroid
|
45 Years
|
70 Years
|
Male
|
Accepts Healthy Volunteers
|
Primary Purpose: Basic Science
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Using Hyperinsulinemic clamp | 1 year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoxia and inflammatory markers | using IHC, qPCR, Western blot | 1 year |
|
Insulin resistance, Inflammation, Hypoxia
|
Insulin Resistance, Hyperinsulinism, Glucose Metabolism Disorders, Metabolic Diseases
|
| Intervention/Treatment |
| --- |
|Procedure: Hyperbaric Oxygen Treatment|Participants will undergo 4 treatments of hyperbaric oxygen. Each treatment consists of 90 minutes compression at 2 atmospheres of pressure, with 30 minutes decompression back to 1 atmosphere, during this time, patients will be treated with 100% Oxygen delivered via a hood system.|
|
Hyperbaric Oxygen Treatment Ameliorates Insulin Resistance
Study Overview
=================
Brief Summary
-----------------
Obesity is an epidemic in Western society and is the biggest risk factor for insulin resistance and type 2 diabetes. The investigators have preliminary evidence showing that hyperbaric oxygen therapy rapidly increases insulin sensitivity in humans. This requires confirmation in a larger population, and with this study the investigators will also test for mechanisms how this occurs. The investigators suspect that modulation of hypoxia and stress response proteins following changes in tissue oxygenation may contribute to these improvements. This study has the potential to yield new and important insights into the insulin resistance in obesity.
Official Title
-----------------
Hyperbaric Oxygen Treatment Ameliorates Insulin Resistance
Conditions
-----------------
Obesity, Type 2 Diabetes
Intervention / Treatment
-----------------
* Procedure: Hyperbaric Oxygen Treatment
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obese men with and without type 2 diabetes aged 45-70 Lean men without type 2 diabetes aged 45-70 Exclusion Criteria: smokers claustrophobic sleep apnoea blood donor exercise more than 2 times per week under certain medications eg: bleomycin,corticosteroid
Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 70 Years
Sexes Eligible for Study
-----------------
Male
Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers
Study Plan
=================
How is the study designed?
-----------------
Design Details
Primary Purpose: Basic Science
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Arms and Interventions
| Intervention/Treatment |
| --- |
|Procedure: Hyperbaric Oxygen Treatment|Participants will undergo 4 treatments of hyperbaric oxygen. Each treatment consists of 90 minutes compression at 2 atmospheres of pressure, with 30 minutes decompression back to 1 atmosphere, during this time, patients will be treated with 100% Oxygen delivered via a hood system.|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Using Hyperinsulinemic clamp | 1 year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoxia and inflammatory markers | using IHC, qPCR, Western blot | 1 year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Insulin resistance, Inflammation, Hypoxia
|
|
NCT05404958
|
Systems Analysis and Improvement Approach to Improve Integration of HIV Prevention and Treatment Services
|
East and Southern Africa is home to 6.2% of the world's population but includes 54% of all people living with HIV (PLWH). In this region, three out of five PLWH are women, and there is a particularly high burden of HIV amongst adolescent girls and young women (AGYW). Over half of African women use family planning (FP) services. Integration of HIV prevention and treatment with FP services holds promise for supporting progress toward the UNAIDS 95-95-95 targets for testing, treatment, and prevention. Nonetheless, integration of even basic HIV prevention and treatment services into FP clinics remains low and how best to integrate these services is still unknown. In a previous trial, the Systems Analysis and Improvement Approach (SAIA), was an effective implementation strategy for improving HIV counseling and testing in a small selection of FP clinics in Mombasa County, Kenya when delivered by research staff. SAIA incorporates a cascade analysis tool, sequential process flow mapping, and cycles of micro-intervention development, implementation, and assessment to improve a care cascade. More data is needed to understand if SAIA is effective for also improving linkage to HIV care and screening and linkage to pre-exposure prophylaxis (PrEP) in FP clinics when SAIA is delivered at scale by Kenyan public health workforce. The first objective of this study is to conduct a cluster-randomized trial evaluating the effectiveness of SAIA versus control (usual procedures with no specific intervention) for increasing HIV counseling, testing, linkage to HIV care, and screening and linkage to PrEP in new FP clients and new and returning AGYW clients. There will be a particular focus on the HIV prevention and treatment of AGYW in this study and any AGYW presenting for FP care will be prioritized. Quantitative and qualitative data will be analyzed using the RE-AIM framework to evaluate the program's Reach, Effectiveness, Adoption, Implementation, and Maintenance. To understand how SAIA could be integrated into national Ministry of Health policies and programs, activity-based costing will be conducted to estimate the budget and program impacts of SAIA, scaled to a County level, from a Ministry of Health perspective. It is hypothesized that compared to control, SAIA will be effective at increasing HIV counseling, HIV testing, linkage to HIV care, and screening and linkage to PrEP for new FP clients and all new and returning AGYW FP clients when delivered at scale by Kenyan public health staff. The implementation evaluation, costing, and budget impact analysis will establish a road map for national-level implementation, positioning Kenya as a global leader in integrating FP/HIV services.
|
AIM 1: To conduct a cluster-randomized trial evaluating the effectiveness of SAIA versus control (usual procedures) for increasing HIV counseling, testing, linkage to care, and screening and linkage to PrEP in new FP clients and new and returning AGYW clients. Quantitative and qualitative data will be analyzed using the RE-AIM framework (21).~1a) Reach: Proportion of intervention arm health facility clients' reached with the intervention~1b) Effectiveness: Compare the effectiveness of SAIA vs. control for increasing rates of HIV counseling, testing, linkage to care, and screening and linkage to PrEP in new FP clients and new and returning AGYW clients~1c) Adoption: Proportion of clinics adopting SAIA; adoption determinants identified using the Implementation Research Logic Model (IRLM) (22) and Organizational Readiness for Implementing Change (ORIC) scale (23)~1d) Implementation: Proportion of FP clinics implementing SAIA with high fidelity at 12 months and at 24 months; barriers and facilitators of implementation at scale by County DOH personnel will be explored using constructs from the Consolidated Framework for Implementation Research (CFIR) and the IRLM (24)~1e) Maintenance: Proportion of FP clinics maintaining SAIA at 12 months and 24 months after introduction AIM 2: To estimate the incremental cost and budget and program impacts of SAIA from a County DOH perspective. We will conduct activity-based costing and develop budget impact scenarios based on SAIA's adoption.
|
Systems Analysis and Improvement Approach to Improve Integration of HIV Prevention and Treatment Services
|
Hiv
|
* Other: Systems Analysis and Improvement Approach (SAIA)
|
Inclusion Criteria:~FP clinics:~-All FP clinics that receive County-supplied FP products will be eligible to participate.~FP clinic managers and staff:~-Any FP clinic manager that is 18 years and older is eligible to be interviewed. -These clinic managers can be male or female.~Kenyan public health staff:~Any Kenyan public health staff that is 18 years and older is eligible to be interviewed.~These public health staff can be male or female.~Exclusion Criteria:~FP clinics:~Any clinics that are expected to close within the next year at the time of study initiation~12 facilities that participated as SAIA intervention facilities in our small-scale trial where the intervention was led by research staff.~FP clinic managers and staff: No exclusion criteria Kenyan public health staff: No exclusion criteria
| null | null |
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a cluster randomized trial enrolling family planning clinics. Participants are FP clinics.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reach HIV counseling | Proportion of FP clients in intervention clinics counseled for HIV out of the total FP clients seen in the clinic | Months 1-12 |
| Effectiveness HIV counseling | Proportion of FP clients (counseled for HIV out of the total FP clients seen in the clinic in intervention vs control clinics | Months 1-12 |
| Reach HIV testing | Proportion of FP clients in intervention clinics counseled for HIV out of the total FP clients seen in the clinic | Months 1-12 |
| Effectiveness HIV testing | Proportion of FP clients tested for HIV out of the total FP clients who should be tested in intervention vs control clinics | Months 1-12 |
| Reach Linked to HIV care | Proportion of HIV seropositive FP clients who are out of care linked to comprehensive HIV care in intervention clinics out of all HIV seropositive FP clients who are out of care | Months 1-12 |
| Effectiveness Linked to HIV care | Proportion of HIV-seropositive FP clients who are out of care then linked to comprehensive HIV care out of all HIV-seropositive FP clients who are out of care in intervention vs control clinics | Months 1-12 |
| Reach Screening and linkage to PrEP | Proportion of HIV seronegative FP clients in intervention clinics screened for PrEP out of all HIV seronegative FP clients~Proportion of HIV seronegative FP clients eligible for PrEP in intervention clinics who are linked to PrEP out of all HIV seronegative FP clients eligible for PrEP | Months 1-12 |
| Effectiveness Screening and linkage to PrEP | 1. Proportion of HIV-seronegative FP clients screened for PrEP out of all HIV-seronegative FP clients in intervention vs control clinics 2. Proportion of HIV-seronegative FP clients who are eligible for PrEP who are linked to PrEP out of all HIV-seronegative FP clients who are eligible for PrEP in intervention vs control clinics 2. Proportion of HIV seronegative FP clients eligible for PrEP in intervention clinics who are linked to PrEP out of all HIV seronegative FP clients eligible for PrEP | Months 1-12 |
| Adoption | 1. Proportion of intervention clinics that participated in the initial training and selected their first micro-intervention | 12 months |
| Adoption | 2. In-depth interviews using the IRLM and CFIR; Administer survey using the ORIC assessment | 12 months |
| Implementation | 1a. Proportion of intervention clinics implementing SAIA with high fidelity~1b. Proportion of intervention clinics implementing SAIA with low fidelity | 12 months |
| Implementation | 1a. Proportion of intervention clinics implementing SAIA with high fidelity~1b. Proportion of intervention clinics implementing SAIA with low fidelity | 24 months |
| Implementation | 2. In-depth interviews with FP clinic staff in intervention clinics and county and national personnel using IRLM and CFIR. | 12 months and 24 months |
| Maintenance | 1a. Proportion of FP clinics with sustained maintenance~1b. Proportion of FP clinics with partial maintenance | 12 & 24 months |
|
HIV prevention and treatment, Family planning, PrEP
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention clinics that implement the Systems Analysis and Improvement Approach<br>Mombasa County public health staff will facilitate SAIA | Other: Systems Analysis and Improvement Approach (SAIA)<br>* What is SAIA? It is a 5-step cycle that is repeated every 4-6 weeks for continuous quality improvement, implemented by Kenyan public health workforce and FP clinic staff, and monitored by Mombasa DOH.~Step 1: Understanding the cascade from FP clinic enrollment to HIV testing to linkage to treatment and prevention services.~Step 2: Use process mapping to identify modifiable bottlenecks. Step 3: Define and implement workflow adaptations to eliminate modifiable bottlenecks.~Step 4: Monitor change in performance. Step 5: Repeat the analysis and improvement cycle (steps 1-4).<br>|
| No Intervention: Usual procedures<br> | |
|
Systems Analysis and Improvement Approach to Improve Integration of HIV Prevention and Treatment Services
Study Overview
=================
Brief Summary
-----------------
East and Southern Africa is home to 6.2% of the world's population but includes 54% of all people living with HIV (PLWH). In this region, three out of five PLWH are women, and there is a particularly high burden of HIV amongst adolescent girls and young women (AGYW). Over half of African women use family planning (FP) services. Integration of HIV prevention and treatment with FP services holds promise for supporting progress toward the UNAIDS 95-95-95 targets for testing, treatment, and prevention. Nonetheless, integration of even basic HIV prevention and treatment services into FP clinics remains low and how best to integrate these services is still unknown. In a previous trial, the Systems Analysis and Improvement Approach (SAIA), was an effective implementation strategy for improving HIV counseling and testing in a small selection of FP clinics in Mombasa County, Kenya when delivered by research staff. SAIA incorporates a cascade analysis tool, sequential process flow mapping, and cycles of micro-intervention development, implementation, and assessment to improve a care cascade. More data is needed to understand if SAIA is effective for also improving linkage to HIV care and screening and linkage to pre-exposure prophylaxis (PrEP) in FP clinics when SAIA is delivered at scale by Kenyan public health workforce. The first objective of this study is to conduct a cluster-randomized trial evaluating the effectiveness of SAIA versus control (usual procedures with no specific intervention) for increasing HIV counseling, testing, linkage to HIV care, and screening and linkage to PrEP in new FP clients and new and returning AGYW clients. There will be a particular focus on the HIV prevention and treatment of AGYW in this study and any AGYW presenting for FP care will be prioritized. Quantitative and qualitative data will be analyzed using the RE-AIM framework to evaluate the program's Reach, Effectiveness, Adoption, Implementation, and Maintenance. To understand how SAIA could be integrated into national Ministry of Health policies and programs, activity-based costing will be conducted to estimate the budget and program impacts of SAIA, scaled to a County level, from a Ministry of Health perspective. It is hypothesized that compared to control, SAIA will be effective at increasing HIV counseling, HIV testing, linkage to HIV care, and screening and linkage to PrEP for new FP clients and all new and returning AGYW FP clients when delivered at scale by Kenyan public health staff. The implementation evaluation, costing, and budget impact analysis will establish a road map for national-level implementation, positioning Kenya as a global leader in integrating FP/HIV services.
Detailed Description
-----------------
AIM 1: To conduct a cluster-randomized trial evaluating the effectiveness of SAIA versus control (usual procedures) for increasing HIV counseling, testing, linkage to care, and screening and linkage to PrEP in new FP clients and new and returning AGYW clients. Quantitative and qualitative data will be analyzed using the RE-AIM framework (21). 1a) Reach: Proportion of intervention arm health facility clients' reached with the intervention 1b) Effectiveness: Compare the effectiveness of SAIA vs. control for increasing rates of HIV counseling, testing, linkage to care, and screening and linkage to PrEP in new FP clients and new and returning AGYW clients 1c) Adoption: Proportion of clinics adopting SAIA; adoption determinants identified using the Implementation Research Logic Model (IRLM) (22) and Organizational Readiness for Implementing Change (ORIC) scale (23) 1d) Implementation: Proportion of FP clinics implementing SAIA with high fidelity at 12 months and at 24 months; barriers and facilitators of implementation at scale by County DOH personnel will be explored using constructs from the Consolidated Framework for Implementation Research (CFIR) and the IRLM (24) 1e) Maintenance: Proportion of FP clinics maintaining SAIA at 12 months and 24 months after introduction AIM 2: To estimate the incremental cost and budget and program impacts of SAIA from a County DOH perspective. We will conduct activity-based costing and develop budget impact scenarios based on SAIA's adoption.
Official Title
-----------------
Systems Analysis and Improvement Approach to Improve Integration of HIV Prevention and Treatment Services
Conditions
-----------------
Hiv
Intervention / Treatment
-----------------
* Other: Systems Analysis and Improvement Approach (SAIA)
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: FP clinics: -All FP clinics that receive County-supplied FP products will be eligible to participate. FP clinic managers and staff: -Any FP clinic manager that is 18 years and older is eligible to be interviewed. -These clinic managers can be male or female. Kenyan public health staff: Any Kenyan public health staff that is 18 years and older is eligible to be interviewed. These public health staff can be male or female. Exclusion Criteria: FP clinics: Any clinics that are expected to close within the next year at the time of study initiation 12 facilities that participated as SAIA intervention facilities in our small-scale trial where the intervention was led by research staff. FP clinic managers and staff: No exclusion criteria Kenyan public health staff: No exclusion criteria
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: Parallel Assignment
Interventional Model Description: This is a cluster randomized trial enrolling family planning clinics. Participants are FP clinics.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention clinics that implement the Systems Analysis and Improvement Approach<br>Mombasa County public health staff will facilitate SAIA | Other: Systems Analysis and Improvement Approach (SAIA)<br>* What is SAIA? It is a 5-step cycle that is repeated every 4-6 weeks for continuous quality improvement, implemented by Kenyan public health workforce and FP clinic staff, and monitored by Mombasa DOH. Step 1: Understanding the cascade from FP clinic enrollment to HIV testing to linkage to treatment and prevention services. Step 2: Use process mapping to identify modifiable bottlenecks. Step 3: Define and implement workflow adaptations to eliminate modifiable bottlenecks. Step 4: Monitor change in performance. Step 5: Repeat the analysis and improvement cycle (steps 1-4).<br>|
| No Intervention: Usual procedures<br> | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reach HIV counseling | Proportion of FP clients in intervention clinics counseled for HIV out of the total FP clients seen in the clinic | Months 1-12 |
| Effectiveness HIV counseling | Proportion of FP clients (counseled for HIV out of the total FP clients seen in the clinic in intervention vs control clinics | Months 1-12 |
| Reach HIV testing | Proportion of FP clients in intervention clinics counseled for HIV out of the total FP clients seen in the clinic | Months 1-12 |
| Effectiveness HIV testing | Proportion of FP clients tested for HIV out of the total FP clients who should be tested in intervention vs control clinics | Months 1-12 |
| Reach Linked to HIV care | Proportion of HIV seropositive FP clients who are out of care linked to comprehensive HIV care in intervention clinics out of all HIV seropositive FP clients who are out of care | Months 1-12 |
| Effectiveness Linked to HIV care | Proportion of HIV-seropositive FP clients who are out of care then linked to comprehensive HIV care out of all HIV-seropositive FP clients who are out of care in intervention vs control clinics | Months 1-12 |
| Reach Screening and linkage to PrEP | Proportion of HIV seronegative FP clients in intervention clinics screened for PrEP out of all HIV seronegative FP clients Proportion of HIV seronegative FP clients eligible for PrEP in intervention clinics who are linked to PrEP out of all HIV seronegative FP clients eligible for PrEP | Months 1-12 |
| Effectiveness Screening and linkage to PrEP | 1. Proportion of HIV-seronegative FP clients screened for PrEP out of all HIV-seronegative FP clients in intervention vs control clinics 2. Proportion of HIV-seronegative FP clients who are eligible for PrEP who are linked to PrEP out of all HIV-seronegative FP clients who are eligible for PrEP in intervention vs control clinics 2. Proportion of HIV seronegative FP clients eligible for PrEP in intervention clinics who are linked to PrEP out of all HIV seronegative FP clients eligible for PrEP | Months 1-12 |
| Adoption | 1. Proportion of intervention clinics that participated in the initial training and selected their first micro-intervention | 12 months |
| Adoption | 2. In-depth interviews using the IRLM and CFIR; Administer survey using the ORIC assessment | 12 months |
| Implementation | 1a. Proportion of intervention clinics implementing SAIA with high fidelity 1b. Proportion of intervention clinics implementing SAIA with low fidelity | 12 months |
| Implementation | 1a. Proportion of intervention clinics implementing SAIA with high fidelity 1b. Proportion of intervention clinics implementing SAIA with low fidelity | 24 months |
| Implementation | 2. In-depth interviews with FP clinic staff in intervention clinics and county and national personnel using IRLM and CFIR. | 12 months and 24 months |
| Maintenance | 1a. Proportion of FP clinics with sustained maintenance 1b. Proportion of FP clinics with partial maintenance | 12 & 24 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV prevention and treatment, Family planning, PrEP
|
||
NCT05091463
|
Non-invasive Spinal Stimulation as an Adjuvant Therapy for Trunk Control After Pediatric SCI
|
The overall purpose of this study is to test the efficacy of multi-modal training combining activity-based locomotor training and transcutaneous spinal stimulation (ABLT+scTS) to improve sitting posture and trunk control in children with a chronic spinal cord injury.~The investigators will recruit 12 participants, ages 3-12 with chronic, acquired SCI, T10 and above and non-ambulatory. The participants in this study will be novices to scTS and AB-LT.
|
This is a within subjects, repeated measures design study. Participants with chronic, acquired SCI (T10 and above and non-ambulatory), ages 3-12 years will serve as their own control and will participate in the studies for all three aims. The participants in this study will be novices to scTS and AB-LT. Medical history and demographics will be collected according to NINDS-Common Data Elements guidelines for pediatric SCI and recommended, standardized outcomes used.~The participants will participate in 60 sessions, 5 days/week for 90 minutes/session. The participants will be assessed at the following time points: Baseline (prior to intervention), after 20 sessions, after 40 sessions and after 60 sessions.~If possible, there will be follow-up assessments occur at 3 months post-60 sessions.~Aim 1: To determine the effects of 60 AB-LT + scTS therapy sessions on sitting posture and trunk control.~Participants will be tested over a total of 4 session (2 pre- and 2 post-60 session intervention). Sessions 1 and 2 will include testing for clinical (Segmental Assessment of Trunk Control (SATCo) and Modified Functional Reach (MFR)) and biomechanical outcomes (Sitting with best posture and MFR), respectively. The two sessions will be conducted within one week.~Aim 2: Determine a) the rate of change in sitting posture and trunk control across, 20, 40, and 60 sessions of AB-LT + scTS, b) the durability of training effects at 3-months follow-up, and c) responsiveness of clinical outcome measures (SATCo and MFR) of trunk control.~Aim 3: To determine residual activation of trunk muscle below the level of the lesion, functional neurophysiological assessment (FNPA) and trunk perturbations will be assess pre- and post-intervention.~The investigators will attain parent/guardian informed consent and participant assent for children > 7 years. Twelve total participants, ages 3-12 years will be recruited and enrolled for all three aims. Participants will be enrolled for 60 sessions (3 months) for the intervention and will be re-tested 3 months post-training.
|
Non-invasive Spinal Stimulation as an Adjuvant Therapy for Trunk Control After Pediatric Spinal Cord Injury
|
Spinal Cord Injuries
|
* Device: Biostim-5/Neostim transcutaneous spinal stimulator
|
Inclusion Criteria:~Chronic (> 1 year since injury), Acquired Upper motor Neuron injury (T10 and above)~Discharged from in-patient rehabilitation~Moderate to severe trunk control deficit as assessed by the Segmental Assessment of Trunk Control (SATCo, score <16/20) OR unable to fully sit upright while lifting their arms or reaching outside of their base of support while maintaining posture~Novice to activity-based locomotor training and transcutaneous spinal stimulation~Exclusion Criteria:~Botox use within the past 3 months~Current oral baclofen use and unwillingness or unable to wean under medical guidance~Baclofen pump use~Musculoskeletal impairment limiting range of motion, unhealed fracture, or other medical complication limiting participation~Prior surgery for scoliosis~Unwillingness to wean from the use of thoraco-lumbosacral orthosis (TLSO) during study~Spina Bifida as etiology of spinal cord injury
|
3 Years
|
12 Years
|
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Segmental Assessment of Trunk Control | Participants will be tested in a seated position with arms and back unsupported on a bench with hip and knee both at 90 degrees of flexion and feet supported. Trunk control will be examined with a therapist progressively changing the level of support, starting at the shoulder girdle and axilla to assess cervical (head) control. They will then progress to the inferior-scapula (mid-thoracic), lower-ribs (lower thoracic), below-ribs (upper lumbar), pelvis (lower lumbar) and no support, to measure full trunk control. Pelvis will be placed in a neutral position via manual support for all testing, except for the no support level. | Change from baseline (Pre-Intervention), after 20 sessions, after 40 sessions, after 60 sessions and after 3 months post 60 sessions(each session is 1.5 hours) |
| Modified Function Reach (MFR) | Participants will be in a sitting position with hip, knees, and ankles in 90 degrees flexion, with feet flat on the floor. The initial reach will be measured using a yard stick with participant reaching (leaning) as far as possible (front, right, and left). Distance covered, in centimeters from initial position to furthest reaching at the level of the 3rd metacarpal, will be recorded in all 3 directions. | Change from baseline (Pre-Intervention), after 20 sessions, after 40 sessions, after 60 sessions and after 3 months post 60 sessions(each session is 1.5 hours) |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Center of Pressure (CoP) displacement | Center of pressure is the location on the supporting surface where the resultant vertical force vector would act if it could be considered to have a single point of application. A shift of CoP is an indirect measure of postural sway and thus a measure of a person's ability to maintain balance. | baseline (Pre-Intervention), After 60 intervention Sessions (each session is 1.5 hours) and 3 months after 60 sessions end |
| Angular Excursions of the Trunk | Degrees of flexion/extension, adduction/abduction and rotation, using wireless motion sensors. | baseline (Pre-Intervention), After 60 Intervention sessions (each session is 1.5 hours) and 3 months after 60 sessions end |
|
Pediatric-onset, Transcutaneous spinal stimulation, Trunk deficit
|
Glycoprotein, Klebsiella pneumoniae, Adjuvants, Immunologic, Immunologic Factors, Physiological Effects of Drugs
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcutaneous spinal stimulation<br>Participants with chronic SCI will receive 60 sessions of activity based-locomotor training (AB-LT) combined with transcutaneous stimulation (scTS). | Device: Biostim-5/Neostim transcutaneous spinal stimulator<br>* Transcutaneous spinal stimulation (scTS): The 5-channel stimulator capable of generating pain-free biphasic rectangular waveform of 0.3 to 1.0 ms pulses with a frequency of 5-10 kHz will be used to stimulate at single or multi-site spinal levels. Transcutaneous stimulation will be delivered in combination with activity based locomotor training in 5-10 minute bouts of stimulation at sub-motor threshold during daily sessions (5x/week) lasting for 90 minutes for a total of 60 sessions of therapy. The sessions will consist of 55-60 minutes on the treadmill for facilitated standing/stepping followed by 30 minutes of activities off the treadmill in sitting, standing, or stepping.<br>|
|
Non-invasive Spinal Stimulation as an Adjuvant Therapy for Trunk Control After Pediatric SCI
Study Overview
=================
Brief Summary
-----------------
The overall purpose of this study is to test the efficacy of multi-modal training combining activity-based locomotor training and transcutaneous spinal stimulation (ABLT+scTS) to improve sitting posture and trunk control in children with a chronic spinal cord injury. The investigators will recruit 12 participants, ages 3-12 with chronic, acquired SCI, T10 and above and non-ambulatory. The participants in this study will be novices to scTS and AB-LT.
Detailed Description
-----------------
This is a within subjects, repeated measures design study. Participants with chronic, acquired SCI (T10 and above and non-ambulatory), ages 3-12 years will serve as their own control and will participate in the studies for all three aims. The participants in this study will be novices to scTS and AB-LT. Medical history and demographics will be collected according to NINDS-Common Data Elements guidelines for pediatric SCI and recommended, standardized outcomes used. The participants will participate in 60 sessions, 5 days/week for 90 minutes/session. The participants will be assessed at the following time points: Baseline (prior to intervention), after 20 sessions, after 40 sessions and after 60 sessions. If possible, there will be follow-up assessments occur at 3 months post-60 sessions. Aim 1: To determine the effects of 60 AB-LT + scTS therapy sessions on sitting posture and trunk control. Participants will be tested over a total of 4 session (2 pre- and 2 post-60 session intervention). Sessions 1 and 2 will include testing for clinical (Segmental Assessment of Trunk Control (SATCo) and Modified Functional Reach (MFR)) and biomechanical outcomes (Sitting with best posture and MFR), respectively. The two sessions will be conducted within one week. Aim 2: Determine a) the rate of change in sitting posture and trunk control across, 20, 40, and 60 sessions of AB-LT + scTS, b) the durability of training effects at 3-months follow-up, and c) responsiveness of clinical outcome measures (SATCo and MFR) of trunk control. Aim 3: To determine residual activation of trunk muscle below the level of the lesion, functional neurophysiological assessment (FNPA) and trunk perturbations will be assess pre- and post-intervention. The investigators will attain parent/guardian informed consent and participant assent for children > 7 years. Twelve total participants, ages 3-12 years will be recruited and enrolled for all three aims. Participants will be enrolled for 60 sessions (3 months) for the intervention and will be re-tested 3 months post-training.
Official Title
-----------------
Non-invasive Spinal Stimulation as an Adjuvant Therapy for Trunk Control After Pediatric Spinal Cord Injury
Conditions
-----------------
Spinal Cord Injuries
Intervention / Treatment
-----------------
* Device: Biostim-5/Neostim transcutaneous spinal stimulator
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chronic (> 1 year since injury), Acquired Upper motor Neuron injury (T10 and above) Discharged from in-patient rehabilitation Moderate to severe trunk control deficit as assessed by the Segmental Assessment of Trunk Control (SATCo, score <16/20) OR unable to fully sit upright while lifting their arms or reaching outside of their base of support while maintaining posture Novice to activity-based locomotor training and transcutaneous spinal stimulation Exclusion Criteria: Botox use within the past 3 months Current oral baclofen use and unwillingness or unable to wean under medical guidance Baclofen pump use Musculoskeletal impairment limiting range of motion, unhealed fracture, or other medical complication limiting participation Prior surgery for scoliosis Unwillingness to wean from the use of thoraco-lumbosacral orthosis (TLSO) during study Spina Bifida as etiology of spinal cord injury
Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 12 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: Transcutaneous spinal stimulation<br>Participants with chronic SCI will receive 60 sessions of activity based-locomotor training (AB-LT) combined with transcutaneous stimulation (scTS). | Device: Biostim-5/Neostim transcutaneous spinal stimulator<br>* Transcutaneous spinal stimulation (scTS): The 5-channel stimulator capable of generating pain-free biphasic rectangular waveform of 0.3 to 1.0 ms pulses with a frequency of 5-10 kHz will be used to stimulate at single or multi-site spinal levels. Transcutaneous stimulation will be delivered in combination with activity based locomotor training in 5-10 minute bouts of stimulation at sub-motor threshold during daily sessions (5x/week) lasting for 90 minutes for a total of 60 sessions of therapy. The sessions will consist of 55-60 minutes on the treadmill for facilitated standing/stepping followed by 30 minutes of activities off the treadmill in sitting, standing, or stepping.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Segmental Assessment of Trunk Control | Participants will be tested in a seated position with arms and back unsupported on a bench with hip and knee both at 90 degrees of flexion and feet supported. Trunk control will be examined with a therapist progressively changing the level of support, starting at the shoulder girdle and axilla to assess cervical (head) control. They will then progress to the inferior-scapula (mid-thoracic), lower-ribs (lower thoracic), below-ribs (upper lumbar), pelvis (lower lumbar) and no support, to measure full trunk control. Pelvis will be placed in a neutral position via manual support for all testing, except for the no support level. | Change from baseline (Pre-Intervention), after 20 sessions, after 40 sessions, after 60 sessions and after 3 months post 60 sessions(each session is 1.5 hours) |
| Modified Function Reach (MFR) | Participants will be in a sitting position with hip, knees, and ankles in 90 degrees flexion, with feet flat on the floor. The initial reach will be measured using a yard stick with participant reaching (leaning) as far as possible (front, right, and left). Distance covered, in centimeters from initial position to furthest reaching at the level of the 3rd metacarpal, will be recorded in all 3 directions. | Change from baseline (Pre-Intervention), after 20 sessions, after 40 sessions, after 60 sessions and after 3 months post 60 sessions(each session is 1.5 hours) |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Center of Pressure (CoP) displacement | Center of pressure is the location on the supporting surface where the resultant vertical force vector would act if it could be considered to have a single point of application. A shift of CoP is an indirect measure of postural sway and thus a measure of a person's ability to maintain balance. | baseline (Pre-Intervention), After 60 intervention Sessions (each session is 1.5 hours) and 3 months after 60 sessions end |
| Angular Excursions of the Trunk | Degrees of flexion/extension, adduction/abduction and rotation, using wireless motion sensors. | baseline (Pre-Intervention), After 60 Intervention sessions (each session is 1.5 hours) and 3 months after 60 sessions end |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pediatric-onset, Transcutaneous spinal stimulation, Trunk deficit
|
NCT03662308
|
Heated Vest for Persons With Spinal Cord Injury
|
Persons with higher levels of spinal cord injury (above the 2nd thoracic vertebrae; tetraplegia) are unable to maintain normal core body temperature (Tcore) when exposed to cool environments. In persons with tetraplegia, even limited exposure to cool temperatures may cause Tcore to approach hypothermic values and impair cognitive performance. Conversely, an increase in Tcore from subnormal to normal range may improve cognitive performance. Prior work has shown that cool seasonal temperatures have an adverse effect on personal comfort and the ability to perform vital daily activities of self-care in persons with tetraplegia. Interventions that address the vulnerability to hypothermia are limited. A self-regulating heated vest designed specifically for persons with tetraplegia is a novel and promising strategy to address this problem. By more effectively maintaining Tcore, the vest can decrease the adverse impact of cool temperatures on comfort, quality of life, and performance of vital daily tasks for Veterans with tetraplegia during the cooler seasons.
|
Persons with spinal cord injury (SCI), particularly cervical injuries (tetraplegia), are unable to effectively regulate core body temperature (Tcore) due to interruption of motor, sensory, and sympathetic pathways. Thus, control of distal extremity vasoconstriction (heat conservation) and shivering thermogenesis (heat production) are impaired, and the ability to maintain a constant Tcore is compromised. Persons with tetraplegia often report feeling cold, frequently present with subnormal Tcore (35-36.5 degrees C), and are particularly vulnerable to hypothermia (Tcore<35 degrees C) and associated impairment in cognitive performance, even when exposed to temperatures that are comfortable for able-bodied (AB) individuals. Cool seasonal temperatures have been shown to have a greater adverse effect on personal comfort, activities of daily living (ADLs), and vital daily activities in persons with tetraplegia than that of AB controls. Conversely, a minimal increase in Tcore from subnormal to normothermia, secondary to ambient heat may improve cognitive performance. Interventions addressing the tendency to poikilothermia and enhanced vulnerability to hypothermia in persons with tetraplegia are limited. Therefore, exploration of safe and efficacious bioengineering solutions to address the physiological, cognitive, and quality of life (QoL) issues associated with the routine exposure to cool temperatures that persons with tetraplegia often encounter is warranted.~The goals of this pilot study are to: 1) fully bench-test the heated vest for safety before performing any human subject testing; 2) study the safety and tolerability of a feedback-controlled heated vest in AB controls; and 3) study the efficacy of this heated vest to minimize the expected decline in Tcore and associated deterioration of cognitive performance during 2 hours of cool exposure in persons with tetraplegia.~In persons with tetraplegia, a two-condition (heated vest, non-heated vest) prospective study is being proposed to compare the physiological and cognitive responses to 2 hours of controlled cool exposure (18 degrees C) with a prototype heated vest vs. a similar, but non-heated vest (control condition). Eight subjects with tetraplegia (C3-T1, AIS A and B) and eight AB controls will be recruited for study participation. Before the prototype is tested on human subjects, it will have been fully bench tested and have satisfied all safety requirements and specifications. AB subjects will be observed to ensure the safety of the vest, which will be accomplished by determining the temperatures of the vest ( 39 degrees C) and subjective thermal sensation of no greater than warm during a cool condition that will be identical to the condition which subjects with SCI will be exposed. Subjects with tetraplegia will test the efficacy of the heated vest, i.e. preventing the expected decline in Tcore and cognitive performance and increase in thermal comfort.~After the feedback-controlled heated vest has been fully bench-tested and has satisfied all safety requirements (interior vest temperature does not exceed 39 degrees C at maximal power) and design specifications (lightweight, slim, easy to don doff), the following specific aims will be addressed:~Primary Specific Aim: In a cool thermal chamber (18 degrees C), AB controls will wear the heated vest at maximal setting for 120 minutes in the seated position to determine (1) maximum temperatures of all areas of the interior (user's side) of the heated vest and (2) subjective comfort of the heated vest (safety testing).~Primary Hypotheses: The study of AB controls will demonstrate (1) All areas under the vest will have temperatures 39 degrees C. (2) All subjects will report a thermal sensation no greater than warm this would include identification of hot spots (Zhang 9-point Thermal Sensation Scale).~Secondary Specific Aim: During exposure to a cool environment (18 degrees C) for up to 120 minutes in the seated position, persons with tetraplegia will wear the heated vest to determine (1) change in Tcore, (2) change in cognitive performance, and (3) change in thermal comfort (efficacy testing).~Secondary Hypotheses: In persons with tetraplegia wearing the heated vest compared to the same persons wearing the non-heated vest, it's expected that (1) 30% of the subjects will have a decline of 0.5 degrees C in Tcore compared with 80% in the control condition, (2) 30% of the subjects will demonstrate a decline of at least 1 T-score in at least one of the following measures: Interference of Stroop Color and Word test, Digit Span of Wechsler Adult Intelligence Scale-Fourth Edition, compared with 80% in the control condition, and (3) a greater percentage of subjects reporting increased thermal comfort (Zhang 6-point Comfort Scale).
|
Developing a Feedback-Controlled Heated Vest to Address Thermoregulatory Dysfunction in Persons With Spinal Cord Injury
|
Spinal Cord Injuries
|
* Device: Heated Vest
* Device: Non-Heated Vest
|
Inclusion Criteria:~Subjects with spinal cord injury (SCI) and able-bodied subjects will be recruited according to the following criteria:~Duration of injury 1 year~Neurological Level of SCI [C3-T1]; American Spinal Injury Association (ASIA) Impairment Scale (AIS) A & B~Euhydration~Subjects will be instructed to avoid caffeine and alcohol~maintain normal salt and water intake~avoid strenuous exercise for 24 hours prior to study~Exclusion Criteria:~Known heart, kidney, peripheral vascular or cerebrovascular disease~High blood pressure~History of Traumatic Brain Injury (TBI) or diagnosed cognitive impairment~Untreated thyroid disease~Diabetes mellitus~Acute illness or infection~Dehydration~Smoking~Pregnant women~BMI>30 kg/m2~Broken, inflamed, or otherwise fragile skin
|
18 Years
|
68 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: After the heated vest has 1) been fully bench-tested and 2) satisfied safety and tolerability testing in able-bodied subjects, it will be tested in persons with tetraplegia using a crossover design with the order of the two visits randomized.~Thermal Challenge with heated vest (subjects with tetraplegia only): Subjects with tetraplegia, while seated and wearing only a standard T-shirt and shorts, will be fitted with an appropriately sized heated vest. Subjects will be transferred to a pre-cooled thermal chamber and data will be collected for up to 2 hours with the self-regulating heated vest.~Thermal Challenge with non-heated vest (subjects with tetraplegia only): The same subjects with tetraplegia (from Visit 2), while seated and wearing only a standard T-shirt and shorts, will be fitted with an appropriately sized, similar, but non-heated vest. Subjects will be transferred to a pre-cooled thermal chamber and data will be collected for up to 2 hours.
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Core Body Temperature (Tcore) | Tcore will be continuously monitored throughout baseline and thermal challenge periods (with heated & non-heated vests) by a TX-2 Rectal probe and Iso-Thermex Multichannel Thermometer (Columbus Instruments, Columbus, OH). The probe will be placed 10 cm beyond the anal sphincter. | Visits 2 & 3 (subjects with tetraplegia only): Continuously throughout baseline & Thermal Challenge (2 hrs) periods. The change in Tcore from baseline to the end of Thermal Challenge will be determined. |
| Change in Cognitive Performance: WAIS-IV | The cognitive battery will be administered once at BL and once after Thermal Challenge in persons with tetraplegia only (Visits 2 & 3). Testing conditions will be identical, quiet, and distraction-free. Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV): Subjects will be asked to repeat 2-9 numbers forward, backward and in ascending order to assess attention, processing speed, and working memory.~Each assessment requires 10 min. | Visits 2 & 3 (subjects with tetraplegia only): At the end baseline (at 15 min) & end of Thermal Challenge (at 120 min) periods. The change in cognitive performance from baseline to the end of Thermal Challenge will be determined. |
| Change in Cognitive Performance: Delayed Recall | Delayed Recall section of the Montreal Cognitive Assessment (MoCA): Subjects will be asked to repeat 5 simple words immediately and then recall them after a 5-minute delay to assess working memory.~Each assessment requires 6 min. | Visits 2 & 3 (subjects with tetraplegia only): At the end baseline (at 15 min) & end of Thermal Challenge (at 120 min) periods. The change in cognitive performance from baseline to the end of Thermal Challenge will be determined. |
| Change in Cognitive Performance: Stroop | Stroop Color and Word: Subjects will be asked to read words of colors, colors of fonts to assess attention and processing speed; color of fonts of words which describe conflicting colors to assess response inhibition (executive functioning). Subjects will practice each of the assessments for approximately 10 seconds prior to the actual test to ensure understanding of the instructions.~Each assessment requires 4 min. | Visits 2 & 3 (subjects with tetraplegia only): At the end baseline (at 15 min) & end of Thermal Challenge (at 120 min) periods. The change in cognitive performance from baseline to the end of Thermal Challenge will be determined. |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Thermal Comfort (TC) | Thermal Comfort will be measured every 10 minutes throughout BL and thermal challenge periods by the Zhang 6-point thermal comfort scale: +3 (very comfortable), +2 (comfortable), +1 (just comfortable), -1 (just uncomfortable), -2 (uncomfortable), and -3 (very uncomfortable). A greater frequency of +1, +2, and +3 scores are considered more desirable than -1, -2, and -3 scores during the Thermal Challenge.~Each assessment requires only the time needed for the subject to respond (typically less than 10 seconds). | Visits 1, 2, & 3 (all subjects): During baseline & every 10 minutes throughout Thermal Challenge (2 hrs). The change in TC from baseline to the end of Thermal Challenge will be determined. |
|
Hypothermia, Body Temperature Regulation, Cognition
|
Spinal Cord Injuries, Wounds and Injuries, Spinal Cord Diseases, Central Nervous System Diseases, Nervous System Diseases, Trauma, Nervous System
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Heated Vest Safety & Comfort (able-bodied subjects)<br>Able-bodied controls will be fitted with an appropriately sized heated vest, while wearing only a standard cotton T-shirt and shorts, and will remain seated in a wheelchair. Subjects will be transferred to a pre-cooled (18 degrees C) thermal chamber and data will be collected for 2 hours with the heated vest on full power. Outcome Variables for Visit 1: Skin thermocouple temperatures, subjective ratings of thermal sensation. | Device: Heated Vest<br>* Heated vest that regulates its heat output based on the user's skin, the user's core temperature, and the ambient temperature<br>* Other names: Feedback-controlled heated vest;|
| Experimental: Heated Vest Efficacy (persons with tetraplegia)<br>Subjects with tetraplegia, while seated and wearing only a standard cotton T-shirt and shorts, will be fitted with an appropriately sized heated vest. Subjects will be transferred to a pre-cooled (18 degrees C) thermal chamber and data will be collected for up to 2 hours with the self-regulating heated vest. Primary Dependent variables: core body temperature (Tcore), cognitive performance, and thermal comfort. | Device: Heated Vest<br>* Heated vest that regulates its heat output based on the user's skin, the user's core temperature, and the ambient temperature<br>* Other names: Feedback-controlled heated vest;|
| Active Comparator: Non-Heated Vest control condition (persons with tetraplegia)<br>The same subjects with tetraplegia from the experimental arm, while seated and wearing only a standard cotton T-shirt and shorts, will be fitted with an appropriately sized, similarly insulated, but non-heated vest (control condition). Subjects will be transferred to a pre-cooled (18 degrees C) thermal chamber and data will be collected for up to 2 hours with the non-heated vest. Primary Dependent variables: core body temperature (Tcore), cognitive performance, and thermal comfort. | Device: Non-Heated Vest<br>* A similarly insulated (compared to the experimental vest), but non-heated vest<br>* Other names: Active comparator vest, control condition;|
|
Heated Vest for Persons With Spinal Cord Injury
Study Overview
=================
Brief Summary
-----------------
Persons with higher levels of spinal cord injury (above the 2nd thoracic vertebrae; tetraplegia) are unable to maintain normal core body temperature (Tcore) when exposed to cool environments. In persons with tetraplegia, even limited exposure to cool temperatures may cause Tcore to approach hypothermic values and impair cognitive performance. Conversely, an increase in Tcore from subnormal to normal range may improve cognitive performance. Prior work has shown that cool seasonal temperatures have an adverse effect on personal comfort and the ability to perform vital daily activities of self-care in persons with tetraplegia. Interventions that address the vulnerability to hypothermia are limited. A self-regulating heated vest designed specifically for persons with tetraplegia is a novel and promising strategy to address this problem. By more effectively maintaining Tcore, the vest can decrease the adverse impact of cool temperatures on comfort, quality of life, and performance of vital daily tasks for Veterans with tetraplegia during the cooler seasons.
Detailed Description
-----------------
Persons with spinal cord injury (SCI), particularly cervical injuries (tetraplegia), are unable to effectively regulate core body temperature (Tcore) due to interruption of motor, sensory, and sympathetic pathways. Thus, control of distal extremity vasoconstriction (heat conservation) and shivering thermogenesis (heat production) are impaired, and the ability to maintain a constant Tcore is compromised. Persons with tetraplegia often report feeling cold, frequently present with subnormal Tcore (35-36.5 degrees C), and are particularly vulnerable to hypothermia (Tcore<35 degrees C) and associated impairment in cognitive performance, even when exposed to temperatures that are comfortable for able-bodied (AB) individuals. Cool seasonal temperatures have been shown to have a greater adverse effect on personal comfort, activities of daily living (ADLs), and vital daily activities in persons with tetraplegia than that of AB controls. Conversely, a minimal increase in Tcore from subnormal to normothermia, secondary to ambient heat may improve cognitive performance. Interventions addressing the tendency to poikilothermia and enhanced vulnerability to hypothermia in persons with tetraplegia are limited. Therefore, exploration of safe and efficacious bioengineering solutions to address the physiological, cognitive, and quality of life (QoL) issues associated with the routine exposure to cool temperatures that persons with tetraplegia often encounter is warranted. The goals of this pilot study are to: 1) fully bench-test the heated vest for safety before performing any human subject testing; 2) study the safety and tolerability of a feedback-controlled heated vest in AB controls; and 3) study the efficacy of this heated vest to minimize the expected decline in Tcore and associated deterioration of cognitive performance during 2 hours of cool exposure in persons with tetraplegia. In persons with tetraplegia, a two-condition (heated vest, non-heated vest) prospective study is being proposed to compare the physiological and cognitive responses to 2 hours of controlled cool exposure (18 degrees C) with a prototype heated vest vs. a similar, but non-heated vest (control condition). Eight subjects with tetraplegia (C3-T1, AIS A and B) and eight AB controls will be recruited for study participation. Before the prototype is tested on human subjects, it will have been fully bench tested and have satisfied all safety requirements and specifications. AB subjects will be observed to ensure the safety of the vest, which will be accomplished by determining the temperatures of the vest ( 39 degrees C) and subjective thermal sensation of no greater than warm during a cool condition that will be identical to the condition which subjects with SCI will be exposed. Subjects with tetraplegia will test the efficacy of the heated vest, i.e. preventing the expected decline in Tcore and cognitive performance and increase in thermal comfort. After the feedback-controlled heated vest has been fully bench-tested and has satisfied all safety requirements (interior vest temperature does not exceed 39 degrees C at maximal power) and design specifications (lightweight, slim, easy to don doff), the following specific aims will be addressed: Primary Specific Aim: In a cool thermal chamber (18 degrees C), AB controls will wear the heated vest at maximal setting for 120 minutes in the seated position to determine (1) maximum temperatures of all areas of the interior (user's side) of the heated vest and (2) subjective comfort of the heated vest (safety testing). Primary Hypotheses: The study of AB controls will demonstrate (1) All areas under the vest will have temperatures 39 degrees C. (2) All subjects will report a thermal sensation no greater than warm this would include identification of hot spots (Zhang 9-point Thermal Sensation Scale). Secondary Specific Aim: During exposure to a cool environment (18 degrees C) for up to 120 minutes in the seated position, persons with tetraplegia will wear the heated vest to determine (1) change in Tcore, (2) change in cognitive performance, and (3) change in thermal comfort (efficacy testing). Secondary Hypotheses: In persons with tetraplegia wearing the heated vest compared to the same persons wearing the non-heated vest, it's expected that (1) 30% of the subjects will have a decline of 0.5 degrees C in Tcore compared with 80% in the control condition, (2) 30% of the subjects will demonstrate a decline of at least 1 T-score in at least one of the following measures: Interference of Stroop Color and Word test, Digit Span of Wechsler Adult Intelligence Scale-Fourth Edition, compared with 80% in the control condition, and (3) a greater percentage of subjects reporting increased thermal comfort (Zhang 6-point Comfort Scale).
Official Title
-----------------
Developing a Feedback-Controlled Heated Vest to Address Thermoregulatory Dysfunction in Persons With Spinal Cord Injury
Conditions
-----------------
Spinal Cord Injuries
Intervention / Treatment
-----------------
* Device: Heated Vest
* Device: Non-Heated Vest
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with spinal cord injury (SCI) and able-bodied subjects will be recruited according to the following criteria: Duration of injury 1 year Neurological Level of SCI [C3-T1]; American Spinal Injury Association (ASIA) Impairment Scale (AIS) A & B Euhydration Subjects will be instructed to avoid caffeine and alcohol maintain normal salt and water intake avoid strenuous exercise for 24 hours prior to study Exclusion Criteria: Known heart, kidney, peripheral vascular or cerebrovascular disease High blood pressure History of Traumatic Brain Injury (TBI) or diagnosed cognitive impairment Untreated thyroid disease Diabetes mellitus Acute illness or infection Dehydration Smoking Pregnant women BMI>30 kg/m2 Broken, inflamed, or otherwise fragile skin
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 68 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
Interventional Model Description: After the heated vest has 1) been fully bench-tested and 2) satisfied safety and tolerability testing in able-bodied subjects, it will be tested in persons with tetraplegia using a crossover design with the order of the two visits randomized. Thermal Challenge with heated vest (subjects with tetraplegia only): Subjects with tetraplegia, while seated and wearing only a standard T-shirt and shorts, will be fitted with an appropriately sized heated vest. Subjects will be transferred to a pre-cooled thermal chamber and data will be collected for up to 2 hours with the self-regulating heated vest. Thermal Challenge with non-heated vest (subjects with tetraplegia only): The same subjects with tetraplegia (from Visit 2), while seated and wearing only a standard T-shirt and shorts, will be fitted with an appropriately sized, similar, but non-heated vest. Subjects will be transferred to a pre-cooled thermal chamber and data will be collected for up to 2 hours.
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Heated Vest Safety & Comfort (able-bodied subjects)<br>Able-bodied controls will be fitted with an appropriately sized heated vest, while wearing only a standard cotton T-shirt and shorts, and will remain seated in a wheelchair. Subjects will be transferred to a pre-cooled (18 degrees C) thermal chamber and data will be collected for 2 hours with the heated vest on full power. Outcome Variables for Visit 1: Skin thermocouple temperatures, subjective ratings of thermal sensation. | Device: Heated Vest<br>* Heated vest that regulates its heat output based on the user's skin, the user's core temperature, and the ambient temperature<br>* Other names: Feedback-controlled heated vest;|
| Experimental: Heated Vest Efficacy (persons with tetraplegia)<br>Subjects with tetraplegia, while seated and wearing only a standard cotton T-shirt and shorts, will be fitted with an appropriately sized heated vest. Subjects will be transferred to a pre-cooled (18 degrees C) thermal chamber and data will be collected for up to 2 hours with the self-regulating heated vest. Primary Dependent variables: core body temperature (Tcore), cognitive performance, and thermal comfort. | Device: Heated Vest<br>* Heated vest that regulates its heat output based on the user's skin, the user's core temperature, and the ambient temperature<br>* Other names: Feedback-controlled heated vest;|
| Active Comparator: Non-Heated Vest control condition (persons with tetraplegia)<br>The same subjects with tetraplegia from the experimental arm, while seated and wearing only a standard cotton T-shirt and shorts, will be fitted with an appropriately sized, similarly insulated, but non-heated vest (control condition). Subjects will be transferred to a pre-cooled (18 degrees C) thermal chamber and data will be collected for up to 2 hours with the non-heated vest. Primary Dependent variables: core body temperature (Tcore), cognitive performance, and thermal comfort. | Device: Non-Heated Vest<br>* A similarly insulated (compared to the experimental vest), but non-heated vest<br>* Other names: Active comparator vest, control condition;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Core Body Temperature (Tcore) | Tcore will be continuously monitored throughout baseline and thermal challenge periods (with heated & non-heated vests) by a TX-2 Rectal probe and Iso-Thermex Multichannel Thermometer (Columbus Instruments, Columbus, OH). The probe will be placed 10 cm beyond the anal sphincter. | Visits 2 & 3 (subjects with tetraplegia only): Continuously throughout baseline & Thermal Challenge (2 hrs) periods. The change in Tcore from baseline to the end of Thermal Challenge will be determined. |
| Change in Cognitive Performance: WAIS-IV | The cognitive battery will be administered once at BL and once after Thermal Challenge in persons with tetraplegia only (Visits 2 & 3). Testing conditions will be identical, quiet, and distraction-free. Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV): Subjects will be asked to repeat 2-9 numbers forward, backward and in ascending order to assess attention, processing speed, and working memory. Each assessment requires 10 min. | Visits 2 & 3 (subjects with tetraplegia only): At the end baseline (at 15 min) & end of Thermal Challenge (at 120 min) periods. The change in cognitive performance from baseline to the end of Thermal Challenge will be determined. |
| Change in Cognitive Performance: Delayed Recall | Delayed Recall section of the Montreal Cognitive Assessment (MoCA): Subjects will be asked to repeat 5 simple words immediately and then recall them after a 5-minute delay to assess working memory. Each assessment requires 6 min. | Visits 2 & 3 (subjects with tetraplegia only): At the end baseline (at 15 min) & end of Thermal Challenge (at 120 min) periods. The change in cognitive performance from baseline to the end of Thermal Challenge will be determined. |
| Change in Cognitive Performance: Stroop | Stroop Color and Word: Subjects will be asked to read words of colors, colors of fonts to assess attention and processing speed; color of fonts of words which describe conflicting colors to assess response inhibition (executive functioning). Subjects will practice each of the assessments for approximately 10 seconds prior to the actual test to ensure understanding of the instructions. Each assessment requires 4 min. | Visits 2 & 3 (subjects with tetraplegia only): At the end baseline (at 15 min) & end of Thermal Challenge (at 120 min) periods. The change in cognitive performance from baseline to the end of Thermal Challenge will be determined. |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Thermal Comfort (TC) | Thermal Comfort will be measured every 10 minutes throughout BL and thermal challenge periods by the Zhang 6-point thermal comfort scale: +3 (very comfortable), +2 (comfortable), +1 (just comfortable), -1 (just uncomfortable), -2 (uncomfortable), and -3 (very uncomfortable). A greater frequency of +1, +2, and +3 scores are considered more desirable than -1, -2, and -3 scores during the Thermal Challenge. Each assessment requires only the time needed for the subject to respond (typically less than 10 seconds). | Visits 1, 2, & 3 (all subjects): During baseline & every 10 minutes throughout Thermal Challenge (2 hrs). The change in TC from baseline to the end of Thermal Challenge will be determined. |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypothermia, Body Temperature Regulation, Cognition
|
NCT04012203
|
Multivariable Recovery After Exercise-induced Muscle Pain in the Forearm Muscles
|
This study investigates the evolution of sensory, motor and tissue variables following exercise-induced pain in wrist extensor muscles in healthy subjects.
|
The aim of this study is to determine how is the normalization process of sensory (pressure pain thresholds, subjective pain sensation, self-recovery perception), motor (maximal isometric strength, active range of motion, manual dexterity) and tissue (myotonometer) variables after an experimental pain model in the extensor forearms muscles, by delayed onset muscle soreness after an eccentric exercise in healthy subjects. This way will be possible to establish 1) if there are differences in the time of normalization for each variable; 2) if there is a correlation between each variable and self-recovery perception.~Seven assessment sessions are performed in a 14-days period. Day 0 (baseline assessment 1), Day 7 (baseline assessment 2, pre exercise), Day 7 (post exercise), Day 8 (24-hours post exercise), Day 9 (48-hours post exercise), Day 10 (72-hours post exercise), Day 14 (1-week post exercise).
|
Temporal Relationship in Recovery of Sensory, Motor and Tissue Variables in an Experimental Exercise-induced Muscle Pain Model of the Wrist Extensor Muscles
|
Musculoskeletal Pain, Healthy, Delayed Onset Muscle Soreness
|
Inclusion Criteria:~Adult healthy subjects of both sexes.~Age: 18-50.~Being free from any pain specific to the upper limb and/or in general.~Exclusion Criteria:~History of acute or chronic painful condition in the previous 3 months.~Regular medication intake for any reason.~History of severe injury in the upper extremity (e.i. fracture).~Prior surgery in the upper limb.~Diagnosed of any chronic pain syndrome (fibromyalgia, migraine, etc.) or severe disease.~Withdrawal Criteria:~Being involved in new physical stimulus, which volunteer is not used to.~Micronutrient supplementation intake.~NSAIDs or other medication intake.
|
18 Years
|
50 Years
|
All
|
Accepts Healthy Volunteers
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Pressure Pain Thresholds: pressure algometry | Changes in pressure pain thresholds will be determined with pressure algometry bilaterally over the forearm, leg and shoulder. Pressure Pain Threshold is defined as the exact time point where the pressure is first being perceived at painful. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
| Changes in subjective perception of pain and recovery: Likert Scale | A modified 7-item Likert Scale for pain (0 No pain - 6 Severely disabling pain) and a visual analogue scale (0-10 cm) for self-recovery perception will be filled up to show subjective perception along the follow-up period. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in mechanical properties of the muscle | Changes in mechanical properties of the muscle will be determined with myotonometer bilaterally over the forearm. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
| Changes in manual dexterity | Changes in manual dexterity of both upper limbs will be assessed by the Nine Hole Peg Test. Participants will had to place 9 pegs in a specifically designed board as fast as possible. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
| Changes in maximal isometric force | Changes in wrist extensors maximal isometric strength will be assessed with hand-held dynamometry. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
| Changes in active range of motion | Changes in active range of motion of the wrist will be assessed in both sides using a digital inclinometer. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
| Level of catastrophizing | Punctuation obtained in Pain Catastrophizing Scale (PCS). It comprises 13 items which focus on thoughts and feelings encountered while experiencing pain. Each item is scored from 0 (not at all) to 4 (all the time) with a total PCS score range from 0-52 points, where higher scores indicating higher levels of pain catastrophizing. | Day-1 (baseline), Day-14 (1-week post-exercise). |
|
Musculoskeletal pain, Delayed Onset Muscle Soreness, Pain mechanisms, Pressure Pain Threshold, Myotonometer, Maximal isometric strength, Manual dexterity
|
Musculoskeletal Pain, Myalgia, Muscular Diseases, Musculoskeletal Diseases, Pain, Neurologic Manifestations, Neuromuscular Diseases, Nervous System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy subjects<br>Participants free from any pain specific to the upper limb during the past 3 months, chronic pain or other disease. | |
|
Multivariable Recovery After Exercise-induced Muscle Pain in the Forearm Muscles
Study Overview
=================
Brief Summary
-----------------
This study investigates the evolution of sensory, motor and tissue variables following exercise-induced pain in wrist extensor muscles in healthy subjects.
Detailed Description
-----------------
The aim of this study is to determine how is the normalization process of sensory (pressure pain thresholds, subjective pain sensation, self-recovery perception), motor (maximal isometric strength, active range of motion, manual dexterity) and tissue (myotonometer) variables after an experimental pain model in the extensor forearms muscles, by delayed onset muscle soreness after an eccentric exercise in healthy subjects. This way will be possible to establish 1) if there are differences in the time of normalization for each variable; 2) if there is a correlation between each variable and self-recovery perception. Seven assessment sessions are performed in a 14-days period. Day 0 (baseline assessment 1), Day 7 (baseline assessment 2, pre exercise), Day 7 (post exercise), Day 8 (24-hours post exercise), Day 9 (48-hours post exercise), Day 10 (72-hours post exercise), Day 14 (1-week post exercise).
Official Title
-----------------
Temporal Relationship in Recovery of Sensory, Motor and Tissue Variables in an Experimental Exercise-induced Muscle Pain Model of the Wrist Extensor Muscles
Conditions
-----------------
Musculoskeletal Pain, Healthy, Delayed Onset Muscle Soreness
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult healthy subjects of both sexes. Age: 18-50. Being free from any pain specific to the upper limb and/or in general. Exclusion Criteria: History of acute or chronic painful condition in the previous 3 months. Regular medication intake for any reason. History of severe injury in the upper extremity (e.i. fracture). Prior surgery in the upper limb. Diagnosed of any chronic pain syndrome (fibromyalgia, migraine, etc.) or severe disease. Withdrawal Criteria: Being involved in new physical stimulus, which volunteer is not used to. Micronutrient supplementation intake. NSAIDs or other medication intake.
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?
-----------------
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy subjects<br>Participants free from any pain specific to the upper limb during the past 3 months, chronic pain or other disease. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Pressure Pain Thresholds: pressure algometry | Changes in pressure pain thresholds will be determined with pressure algometry bilaterally over the forearm, leg and shoulder. Pressure Pain Threshold is defined as the exact time point where the pressure is first being perceived at painful. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
| Changes in subjective perception of pain and recovery: Likert Scale | A modified 7-item Likert Scale for pain (0 No pain - 6 Severely disabling pain) and a visual analogue scale (0-10 cm) for self-recovery perception will be filled up to show subjective perception along the follow-up period. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in mechanical properties of the muscle | Changes in mechanical properties of the muscle will be determined with myotonometer bilaterally over the forearm. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
| Changes in manual dexterity | Changes in manual dexterity of both upper limbs will be assessed by the Nine Hole Peg Test. Participants will had to place 9 pegs in a specifically designed board as fast as possible. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
| Changes in maximal isometric force | Changes in wrist extensors maximal isometric strength will be assessed with hand-held dynamometry. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
| Changes in active range of motion | Changes in active range of motion of the wrist will be assessed in both sides using a digital inclinometer. | Day-1 (baseline assessment 1), Day-7 (baseline assessment 2, pre exercise), Day-7 (post-exercise), Day-8 (24 hours post-exercise), Day-9 (48 hours post-exercise), Day-10 (72 hours post-exercise), Day-14 (1-week post-exercise). |
| Level of catastrophizing | Punctuation obtained in Pain Catastrophizing Scale (PCS). It comprises 13 items which focus on thoughts and feelings encountered while experiencing pain. Each item is scored from 0 (not at all) to 4 (all the time) with a total PCS score range from 0-52 points, where higher scores indicating higher levels of pain catastrophizing. | Day-1 (baseline), Day-14 (1-week post-exercise). |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Musculoskeletal pain, Delayed Onset Muscle Soreness, Pain mechanisms, Pressure Pain Threshold, Myotonometer, Maximal isometric strength, Manual dexterity
|
||
NCT04138836
|
Assess the Drug Interactions of BBT-877 and Midazolam, Itraconazole, and Esomeprazole in Healthy Adult Subjects
|
Study to determine the effect of multiple-dose BBT-877 on the single-dose pharmacokinetics of midazolam, the safety and tolerability of a single dose of BBT-877 administered alone and with multiple doses of itraconazole, and the effect of multiple-dose esomeprazole on the single-dose pharmacokinetics of BBT-877, in healthy adult subjects.
|
A 3-Part, Phase 1 Study to Assess the Drug Interactions of BBT-877 and Midazolam, Itraconazole, and Esomeprazole in Healthy Adult Subjects
|
Healthy Participants
|
* Drug: BBT-877
* Drug: Midazolam
* Drug: Itraconazole
* Drug: Esomeprazole
|
Inclusion Criteria:~Healthy adult male and/or female (non-childbearing potential only), 19 to 55 years of age, inclusive, at screening.~Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose and throughout the study.~BMI ≥ 18.5 and ≤ 32.0 kg/m2 and weight ≥ 50 kg at screening.~Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, as deemed by the PI or designee.~No clinically significant history or presence of ECG findings as judged by the PI or qualified designee at screening and first check-in.~For a female, must be of non-childbearing potential.~A non-vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study drug.~If male, must agree to not donate sperm from the first dose until 90 days after the last dose of study drug(s).~Must have the ability to understand and sign a written informed consent form (ICF), which must be obtained prior to initiation of study procedures, and be willing and able to comply with the protocol requirements as outlined in the ICF.~Exclusion Criteria:~Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.~History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.~History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.~History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose or regular alcohol consumption within 6 months prior to the first dose.~History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds.~History of anemia or history of decreased red blood cells (RBC).~Estimated creatinine clearance <80 mL/min at screening.~Liver function tests (serum ALT, AST, alkaline phosphatase) and serum bilirubin (total and direct) > upper limit of normal at screening or first check-in.~Baseline hemoglobin, hematocrit, RBC < lower limit of normal at screening and Day -1 of Period 1.~Female subjects who are of childbearing potential.~Female subjects who are pregnant or lactating.~Positive urine drug or alcohol results at screening or first check-in.~Positive urine cotinine at screening.~Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
|
19 Years
|
55 Years
|
All
|
Accepts Healthy Volunteers
|
Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (the area under the curve) [Pharmacokinetics] | AUC for midazolam and 1-OH-midazolam with and without BBT-877 (Arm 1), and for BBT-877 with and without itraconazole (Arm 2) or esomeprazole (Arm 3) | Day 1 of period 1 and Day 10 (Arm 1), 5 (Arm 2), or 5 (Arm 3) of period 2 |
| Cmax (peak concentration) [Pharmacokinetics] | Cmax for midazolam and 1-OH-midazolam with and without BBT-877 (Arm 1), and for BBT-877 with and without itraconazole (Arm 2) or esomeprazole (Arm 3) | Day 1 of period 1 and Day 10 (Arm 1), 5 (Arm 2), or 5 (Arm 3) of period 2 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma LPA (Lysophosphatidic acid) concentration [Pharmacodynamics (Arm 2 and 3)] | plasma LPA (18:2 and 20:4) concentrations over time and percent decrease from baseline LPA level | Day 1 of period 1 and Day 10 (Arm 1), 5 (Arm 2), or 5 (Arm 3) of period 2 |
| Incidence of adverse events [Safety and tolerability] | Incidence of adverse events | Up to 14 days after the last study drug administration |
|
Itraconazole, Midazolam, Esomeprazole, Adjuvants, Anesthesia, Hypnotics and Sedatives, Central Nervous System Depressants, Physiological Effects of Drugs, Anti-Anxiety Agents, Tranquilizing Agents, Psychotropic Drugs, Anesthetics, Intravenous, Anesthetics, General, Anesthetics, GABA Modulators, GABA Agents, Neurotransmitter Agents, Molecular Mechanisms of Pharmacological Action, Anti-Ulcer Agents, Gastrointestinal Agents, Proton Pump Inhibitors, Enzyme Inhibitors, Antifungal Agents, Anti-Infective Agents, 14-alpha Demethylase Inhibitors, Cytochrome P-450 Enzyme Inhibitors, Steroid Synthesis Inhibitors, Hormone Antagonists, Hormones, Hormone Substitutes, and Hormone Antagonists, Cytochrome P-450 CYP3A Inhibitors
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midazolam<br> | Drug: BBT-877<br>* BBT-877 oral capsule.<br>Drug: Midazolam<br>* Midazolam oral syrup.<br>|
| Experimental: Itraconazole<br> | Drug: BBT-877<br>* BBT-877 oral capsule.<br>Drug: Itraconazole<br>* Itraconazole oral capsule.<br>|
| Experimental: Esomeprazole<br> | Drug: BBT-877<br>* BBT-877 oral capsule.<br>Drug: Esomeprazole<br>* Esomeprazole oral capsule.<br>|
|
Assess the Drug Interactions of BBT-877 and Midazolam, Itraconazole, and Esomeprazole in Healthy Adult Subjects
Study Overview
=================
Brief Summary
-----------------
Study to determine the effect of multiple-dose BBT-877 on the single-dose pharmacokinetics of midazolam, the safety and tolerability of a single dose of BBT-877 administered alone and with multiple doses of itraconazole, and the effect of multiple-dose esomeprazole on the single-dose pharmacokinetics of BBT-877, in healthy adult subjects.
Official Title
-----------------
A 3-Part, Phase 1 Study to Assess the Drug Interactions of BBT-877 and Midazolam, Itraconazole, and Esomeprazole in Healthy Adult Subjects
Conditions
-----------------
Healthy Participants
Intervention / Treatment
-----------------
* Drug: BBT-877
* Drug: Midazolam
* Drug: Itraconazole
* Drug: Esomeprazole
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adult male and/or female (non-childbearing potential only), 19 to 55 years of age, inclusive, at screening. Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose and throughout the study. BMI ≥ 18.5 and ≤ 32.0 kg/m2 and weight ≥ 50 kg at screening. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, as deemed by the PI or designee. No clinically significant history or presence of ECG findings as judged by the PI or qualified designee at screening and first check-in. For a female, must be of non-childbearing potential. A non-vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study drug. If male, must agree to not donate sperm from the first dose until 90 days after the last dose of study drug(s). Must have the ability to understand and sign a written informed consent form (ICF), which must be obtained prior to initiation of study procedures, and be willing and able to comply with the protocol requirements as outlined in the ICF. Exclusion Criteria: Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee. History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dose or regular alcohol consumption within 6 months prior to the first dose. History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds. History of anemia or history of decreased red blood cells (RBC). Estimated creatinine clearance <80 mL/min at screening. Liver function tests (serum ALT, AST, alkaline phosphatase) and serum bilirubin (total and direct) > upper limit of normal at screening or first check-in. Baseline hemoglobin, hematocrit, RBC < lower limit of normal at screening and Day -1 of Period 1. Female subjects who are of childbearing potential. Female subjects who are pregnant or lactating. Positive urine drug or alcohol results at screening or first check-in. Positive urine cotinine at screening. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
Ages Eligible for Study
-----------------
Minimum Age: 19 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: Single Group Assignment
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midazolam<br> | Drug: BBT-877<br>* BBT-877 oral capsule.<br>Drug: Midazolam<br>* Midazolam oral syrup.<br>|
| Experimental: Itraconazole<br> | Drug: BBT-877<br>* BBT-877 oral capsule.<br>Drug: Itraconazole<br>* Itraconazole oral capsule.<br>|
| Experimental: Esomeprazole<br> | Drug: BBT-877<br>* BBT-877 oral capsule.<br>Drug: Esomeprazole<br>* Esomeprazole oral capsule.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (the area under the curve) [Pharmacokinetics] | AUC for midazolam and 1-OH-midazolam with and without BBT-877 (Arm 1), and for BBT-877 with and without itraconazole (Arm 2) or esomeprazole (Arm 3) | Day 1 of period 1 and Day 10 (Arm 1), 5 (Arm 2), or 5 (Arm 3) of period 2 |
| Cmax (peak concentration) [Pharmacokinetics] | Cmax for midazolam and 1-OH-midazolam with and without BBT-877 (Arm 1), and for BBT-877 with and without itraconazole (Arm 2) or esomeprazole (Arm 3) | Day 1 of period 1 and Day 10 (Arm 1), 5 (Arm 2), or 5 (Arm 3) of period 2 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma LPA (Lysophosphatidic acid) concentration [Pharmacodynamics (Arm 2 and 3)] | plasma LPA (18:2 and 20:4) concentrations over time and percent decrease from baseline LPA level | Day 1 of period 1 and Day 10 (Arm 1), 5 (Arm 2), or 5 (Arm 3) of period 2 |
| Incidence of adverse events [Safety and tolerability] | Incidence of adverse events | Up to 14 days after the last study drug administration |
|
||
NCT03873467
|
Group Lifestyle Balance™ for Individuals With Stroke (GLB-CVA)
|
The purpose of this RCT is to examine the efficacy of the Group Lifestyle Balance (GLB) program adapted for people with stroke (CVA) on primary (weight) and secondary outcomes at 3, 6, 12 months from enrollment into the program.
|
Weight gain greatly increases the risk of chronic diseases after stroke such as diabetes, metabolic syndrome, pulmonary and heart disease. Approaches to weight-loss are lacking, yet necessary, due to the unique physiological and cognitive needs of persons with CVA. There is evidence that interventions that improve physical activity and healthy eating behaviors concurrently offer greatest potential for weight-loss. The Group Lifestyle Balance (GLB) intervention is a 12-month, evidence-based weight-loss program that has been used extensively with the general population, but not with people after CVA. Investigators modified the program to meet the needs of people post stroke (GLB-CVA).~Study Aims:~The study consists of five specific aims.~Specific Aim 1: To create an appropriate adaptation of the DPP-GLB program that meets the unique needs of people post CVA (GLB-CVA) using a Community-Based Participatory Research approach and Advisory Board of key stakeholders (patients, caregivers, clinicians, researchers).~Specific Aim 2: To establish the feasibility of delivering the GLB-CVA intervention.~Specific Aim 3: Conduct a randomized controlled trial (RCT) to examine the effectiveness of the GLB-CVA on primary and secondary outcomes in the intervention group compared to the wait-list control group at 3, 6, and 12 months from baseline.~Specific Aim 4: Describe the effect of the GLB-CVA on metabolic biomarkers in the experimental group compared to the wait-list control group at baseline, 3, and 6 months.~Specific Aim 5: Describe the association between biomarkers of neurodegeneration and physiologic, functional, and patient reported outcomes at baseline, 3, and 6 months.
|
Efficacy of an Evidence-based Healthy Lifestyle Intervention for People Following CVA
|
Stroke
|
* Behavioral: Group Lifestyle Balance
* Other: Usual Care
|
Inclusion Criteria:~18 to 85 years of age~BMI ≥25~All types of stroke~At least 12 months post first stroke~Physician approval~Exclusion Criteria:~Low cognition~Not fluent in the English language~Conditions for which physical activity is contraindicated~Taking medication for type 2 diabetes~Residing in a hospital, acute rehabilitation setting, or skilled nursing facility~Pregnancy~Pre-existing diagnosis of an eating disorder
|
18 Years
|
85 Years
|
All
|
No
|
Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Controlled Trial (RCT). Participants will be randomized into one of two groups: (1) the GLB Intervention Group and (2) the wait-list controlled group.
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight | Will be obtained using the same scale over the study period that is accessible to people with and without a mobility device (e.g., walker; wheelchair). | Baseline, 3, 6, 12 months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Activity | Accelerometers will be worn by participants for two weeks around each study visit to objectively track physical activity participation (amount and intensity). Participants will be given the Actigraph accelerometer at the beginning of the study and will be provided with verbal and written instructions. | Baseline, 3, 6, 12 months |
| Arm Circumference | Arm circumference measured at mid-upper arm following ACSM guidelines. A total of three measurements will be taken and an average of the three will be used. Measurements will be taken in centimeters. | Baseline, 3, 6, 12 months |
| Blood Pressure | Using an automatic cuff (average of three readings, patient seated) diastolic and systolic scores will be recorded | Baseline, 3, 6, 12 months |
| Cholesterol | Fasting venous sample will be obtained. Coordinators are trained phlebotomists. | Baseline, 3, 6, 12 months |
| Risk of Diabetes | The Framingham Heart Study diabetes risk score will be calculated using predictors including age, gender, fasting glucose, BMI, HDL cholesterol and triglyceride levels, blood pressure, and parental history. Risk score calculator and regression model are free and used in GLB weight-loss trials. Risk score calculator and regression model are free and used in GLB weight-loss studies. Each risk predictor is assigned points ranging from 2-10. Risk factors are combined and a total score is calculated, with higher scores designating greater 8-year risk.The age range for this score is 45 years to 64 years, and therefore only individuals within this age will have calculated scores. Furthermore, the minimum cut-off score is 3. | Baseline, 3, 6, 12 months |
| 10 Meter Walk Test (10MWT) | Assesses walking speed in (m/s) which is correlated to mobility in the community, capacity to perform ADLs, risk of falls, re-hospitalization, and risk of cognitive decline. | Baseline, 3, 6, 12 months |
| 6 Minute Walk Test (6MWT) | Assesses distance walked over 6 minutes as a sub-maximal test of aerobic capacity. Endurance is essential to participate in community-based activities. | Baseline, 3, 6, 12 months |
| Perceived Social Support | The Multidimensional Scale of Perceived Social Support (MSPSS) is comprised of 12 questions with a 4-item subscale. The MSPSS is designed to assess perception of social support from friends, family, and significant others | Baseline and 12 months |
| Self-reported activities of health using the Self-Rated Abilities for Health Practice scale | Measure includes 28 items that assess health practices among people with disabilities and yields a total Health Practices score plus 4 subscales scores regarding Exercise, Nutrition, Health Practices, and Psychological Well Being. Items are rated on a 5-point scale from 0 'not at all' to 4 'completely.' Scores range from 0-28 with higher scores indicating higher exercise self-efficacy. | Baseline and 12 months |
| Neighborhood walkability using Walk Score® | Walk Score® is publicly available and measures the walkability of any address using a patented system. For each address, Walk Score ® analyzes hundreds of walking routes to nearby amenities and awards points based on distance to each amenity. Walk Score® also measures pedestrian friendliness by analyzing population density and road metrics such a block length and intersection density. Scores are given on a scale of 0 to 100. | Baseline |
| Resting Metabolic Rate | MedGem® is an FDA cleared and validated indirect calorimetry device. It is handheld and measures oxygen consumption (V02) to determine resting metabolic rate (RMR). | Baseline |
| Behavioral Risk Factor Surveillance | The BRFSS is a state-based system of health surveys that collects information on health risk behaviors, preventative health practices, and health care access primarily related to chronic disease and injury. The GLB-TBI uses the two subscales of Healthy Eating and Physical Activity from the 2017 version of the BRFSS. It consists of 14 items. | Baseline, 3, 6, 12 months |
| Participant quality of ife | Quality of life will be assess using the stroke impact scale (SIS), which assesses 8 dimensions of health-related QOL specific to people post CVA including subscales (using a 5pt Likert scale) assessing strength, memory and thinking, emotion, communication, activities of daily living, mobility, hand function, and participation/role function | Baseline, 6, 12 months |
| Stressful Life Events using the Holmes and Rahe Stress Inventory | This inventory consists of 40 life events and asks the participant to recall if any of the events happened within the previous year (e.g., death of spouse; personal illness; change in sleep). Endorsement of these events are totaled and higher scores indicate a greater amount of stressful life events. Point values for the Holmes and Rahe Stress Inventory were weighted and summed for each individual based on scoring instructions. Individuals who scored 150 points or less were categorized as low susceptibility to a health breakdown in the next two years, 151-300 points were 50% chance of health breakdown, and 301 points or more were 80% chance of health breakdown. | Baseline and 12 months |
| Executive Function and Cognition using the Montreal Cognitive Assessment | The MOCA is a brief, 8-section assessment of various cognitive domains including executive function, memory, language, attention, concentration, orientation, and working memory in neurologic populations.Each item on the MOCA is allocated a set of points adding up to 30. | Baseline, 3, and 12 months |
| Habit Formation | The self-reported habit index (SRHI) measures the self-reported perceptions of habit strength for an identified behavior. It consists of 12 items for each selected behavior and uses a 7-point Likert scale from completely disagree to completely agree. Higher totals represent greater perception of habit strength. The SRHI showed high reliability across four studies with alphas of .89, .92, .89, .94, .95, .94, and .85. | Baseline, 3, and 12 months |
| Stroke Severity | The Modified Rankin Scale (MRS) measures the degree of disability or dependence for daily activities of people who have had a stroke. The MRS is an ordinal scale with six categories ranging from zero (no symptoms) to five (complete physical dependence). A score of six signifies death. | Baseline |
| Pain Interference | The Pain Interference-Short Form is taken from the Patient-Reported Outcomes Measurement Information System (PROMIS). This measure is used to assess adult self-reported consequences of pain and pain consequences (e.g. interference in social, cognitive, emotional, physical and recreational activities). This measure consists of four questions with five response option ranging from one to five. The sum of all responses creates a total raw score. This measure is normed to the US general population. | Baseline, 3, 6, and 12 months |
| Sleep Disturbance | The Sleep Disturbance-Short Form 4a is taken from the Patient-Reported Outcomes Measurement Information System (PROMIS) and used to assess adult sleep disturbance profiles. This measure has four questions, each with five response options ranging in value from one to five. The sum of each response creates a total raw score. The measure is normed to the US general population. | Baseline, 3, 6, 12 months |
| Waist Circumference | Waist circumference will be measured at the umbilicus following ACSM guidelines. A total of three measurements will be taken and an average of the three will be the final measurement used. Measurements will be scored in centimeters. | Baseline, 3, 6, and 12 months |
| HbA1c | Fasting venous sample will be obtained for hemoglobin a1c to assess average blood sugar level over the past 2-3 months. Coordinators are trained phlebotomists. | Baseline, 3, 6, and 12 months |
| Triglycerides | Fasting venous sample will be obtained. Coordinators are trained phlebotomists. | Baseline, 3, 6, 12 months |
| Blood Glucose | Fasting venous sample will be obtained. Coordinators are trained phlebotomists. | Baseline, 3, 6, 12 months |
| Biomarker Analysis | Isrin, Angiogenic factors (VEGF), Total Homocysteine, Lipoprotein-associated phospholipase A2 (Lp-PLA2), ICF-1, Brain derived neurotrophic factor (BDNF), and Tau proteins (total and phosphorylated) will be drawn to assess relationships with outcome variables. | Baseline, 3, and 6 months |
| Stages of Change | A modified version of Prochaska and DiClemente's Stages of Change model will be administered to measure readiness for behavior change. The measure consists of two behaviors (eating and exercise) with five questions each related to a stage of change (precontemplation, contemplation, preparation, action, maintenance). | Baseline, 3, 6, and 12 months |
| Metabolic Score Calculator (MetS) | The metabolic score calculator will be used at all time points to determine the risk for metabolic syndrome. The following variables will be used to determine metabolic risk using the free metabolic risk calculator: gender, race and ethnicity, systolic blood pressure, fasting glucose, triglycerides, high-density lipoprotein (HDL), weight, height, and waist circumference. Scores are calculated are standardized to the general population. | Baseline, 3, 6, and 12 months |
| CRISIS (CoRonavIruS Health Impact Survey) V0.3 Adult Baseline Form | This self-report survey was developed by the National Institute of Mental Health. The full survey consists of 64 questions with an open-ended section at the end to elicit concerns and feedback related to the effects of COVID-19. For this current study, however, only sections on Exposure Status (10 items), Life Changes (15 items), and Emotions/Worries (7 items), and the open-ended question will be asked. Questions are asked over the past two weeks. | Up to 12 months |
| PROMIS Social Isolation Short Form 4a | The Social Isolation Short-Form 4a is taken from the Patient-Reported Outcomes Measurement Information System (PROMIS). This form assesses the perceptions of being avoided, excluded, detached, disconnected from, or unknown by, others. There is no timeframe for the form. The measure is normed to the US population. | Up to 12 months |
| Media Questionnaire | To assess media exposure and fear of media exposure during COVID-19 we have added 6 questions. These are asked over the past two weeks. These questions address time spent watching the television, listening to radio, reading the newspaper, and searching the internet and social media. In addition, a 6th question related to fear is asked using a 5-point Likert scale. | Up to 12 months |
|
Group Lifestyle Balance, Physical Activity, Stroke, Weight-loss, Dietary Behaviors
|
Stroke, Cerebrovascular Disorders, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Cardiovascular Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLB Weight-Loss Intervention<br>The GLB program, adapted for individuals with stroke, will be delivered to participants over a 12-month period, divided into 22 in-person or virtual, group sessions. The intervention promotes 5-7% weight-loss by reducing calories and increasing exercise (150 minutes of moderate physical activity per week). | Behavioral: Group Lifestyle Balance<br>* The Group Lifestyle Balance (GLB) program is a self-management intervention that has been shown to result in weight-loss and reduce the risk for Type 2 diabetes through increased physical activity and healthy eating behaviors in the general population. The GLB is a direct adaptation of the Diabetes Prevention Program, both developed at the Diabetes Prevention and Support Center at the University of Pittsburgh. The GLB is designed for delivery in a group-based, community setting, and has resulted in weight-loss in a variety of settings, such as community centers, churches, worksites, and healthcare systems. The GLB curriculum used in this study has been adapted for people with stroke.<br>|
| Other: Wait-List Control<br>The wait-list control group will receive no intervention for 6 months after enrollment. After the 6 month control period, the wait-list control group will receive the GLB Intervention. | Other: Usual Care<br>* Participants randomized to the wait-list control group will receive usual care for 6 months before beginning the modified GLB program.<br>|
|
Group Lifestyle Balance™ for Individuals With Stroke (GLB-CVA)
Study Overview
=================
Brief Summary
-----------------
The purpose of this RCT is to examine the efficacy of the Group Lifestyle Balance (GLB) program adapted for people with stroke (CVA) on primary (weight) and secondary outcomes at 3, 6, 12 months from enrollment into the program.
Detailed Description
-----------------
Weight gain greatly increases the risk of chronic diseases after stroke such as diabetes, metabolic syndrome, pulmonary and heart disease. Approaches to weight-loss are lacking, yet necessary, due to the unique physiological and cognitive needs of persons with CVA. There is evidence that interventions that improve physical activity and healthy eating behaviors concurrently offer greatest potential for weight-loss. The Group Lifestyle Balance (GLB) intervention is a 12-month, evidence-based weight-loss program that has been used extensively with the general population, but not with people after CVA. Investigators modified the program to meet the needs of people post stroke (GLB-CVA). Study Aims: The study consists of five specific aims. Specific Aim 1: To create an appropriate adaptation of the DPP-GLB program that meets the unique needs of people post CVA (GLB-CVA) using a Community-Based Participatory Research approach and Advisory Board of key stakeholders (patients, caregivers, clinicians, researchers). Specific Aim 2: To establish the feasibility of delivering the GLB-CVA intervention. Specific Aim 3: Conduct a randomized controlled trial (RCT) to examine the effectiveness of the GLB-CVA on primary and secondary outcomes in the intervention group compared to the wait-list control group at 3, 6, and 12 months from baseline. Specific Aim 4: Describe the effect of the GLB-CVA on metabolic biomarkers in the experimental group compared to the wait-list control group at baseline, 3, and 6 months. Specific Aim 5: Describe the association between biomarkers of neurodegeneration and physiologic, functional, and patient reported outcomes at baseline, 3, and 6 months.
Official Title
-----------------
Efficacy of an Evidence-based Healthy Lifestyle Intervention for People Following CVA
Conditions
-----------------
Stroke
Intervention / Treatment
-----------------
* Behavioral: Group Lifestyle Balance
* Other: Usual Care
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 to 85 years of age BMI ≥25 All types of stroke At least 12 months post first stroke Physician approval Exclusion Criteria: Low cognition Not fluent in the English language Conditions for which physical activity is contraindicated Taking medication for type 2 diabetes Residing in a hospital, acute rehabilitation setting, or skilled nursing facility Pregnancy Pre-existing diagnosis of an eating disorder
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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Controlled Trial (RCT). Participants will be randomized into one of two groups: (1) the GLB Intervention Group and (2) the wait-list controlled group.
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLB Weight-Loss Intervention<br>The GLB program, adapted for individuals with stroke, will be delivered to participants over a 12-month period, divided into 22 in-person or virtual, group sessions. The intervention promotes 5-7% weight-loss by reducing calories and increasing exercise (150 minutes of moderate physical activity per week). | Behavioral: Group Lifestyle Balance<br>* The Group Lifestyle Balance (GLB) program is a self-management intervention that has been shown to result in weight-loss and reduce the risk for Type 2 diabetes through increased physical activity and healthy eating behaviors in the general population. The GLB is a direct adaptation of the Diabetes Prevention Program, both developed at the Diabetes Prevention and Support Center at the University of Pittsburgh. The GLB is designed for delivery in a group-based, community setting, and has resulted in weight-loss in a variety of settings, such as community centers, churches, worksites, and healthcare systems. The GLB curriculum used in this study has been adapted for people with stroke.<br>|
| Other: Wait-List Control<br>The wait-list control group will receive no intervention for 6 months after enrollment. After the 6 month control period, the wait-list control group will receive the GLB Intervention. | Other: Usual Care<br>* Participants randomized to the wait-list control group will receive usual care for 6 months before beginning the modified GLB program.<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight | Will be obtained using the same scale over the study period that is accessible to people with and without a mobility device (e.g., walker; wheelchair). | Baseline, 3, 6, 12 months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Activity | Accelerometers will be worn by participants for two weeks around each study visit to objectively track physical activity participation (amount and intensity). Participants will be given the Actigraph accelerometer at the beginning of the study and will be provided with verbal and written instructions. | Baseline, 3, 6, 12 months |
| Arm Circumference | Arm circumference measured at mid-upper arm following ACSM guidelines. A total of three measurements will be taken and an average of the three will be used. Measurements will be taken in centimeters. | Baseline, 3, 6, 12 months |
| Blood Pressure | Using an automatic cuff (average of three readings, patient seated) diastolic and systolic scores will be recorded | Baseline, 3, 6, 12 months |
| Cholesterol | Fasting venous sample will be obtained. Coordinators are trained phlebotomists. | Baseline, 3, 6, 12 months |
| Risk of Diabetes | The Framingham Heart Study diabetes risk score will be calculated using predictors including age, gender, fasting glucose, BMI, HDL cholesterol and triglyceride levels, blood pressure, and parental history. Risk score calculator and regression model are free and used in GLB weight-loss trials. Risk score calculator and regression model are free and used in GLB weight-loss studies. Each risk predictor is assigned points ranging from 2-10. Risk factors are combined and a total score is calculated, with higher scores designating greater 8-year risk.The age range for this score is 45 years to 64 years, and therefore only individuals within this age will have calculated scores. Furthermore, the minimum cut-off score is 3. | Baseline, 3, 6, 12 months |
| 10 Meter Walk Test (10MWT) | Assesses walking speed in (m/s) which is correlated to mobility in the community, capacity to perform ADLs, risk of falls, re-hospitalization, and risk of cognitive decline. | Baseline, 3, 6, 12 months |
| 6 Minute Walk Test (6MWT) | Assesses distance walked over 6 minutes as a sub-maximal test of aerobic capacity. Endurance is essential to participate in community-based activities. | Baseline, 3, 6, 12 months |
| Perceived Social Support | The Multidimensional Scale of Perceived Social Support (MSPSS) is comprised of 12 questions with a 4-item subscale. The MSPSS is designed to assess perception of social support from friends, family, and significant others | Baseline and 12 months |
| Self-reported activities of health using the Self-Rated Abilities for Health Practice scale | Measure includes 28 items that assess health practices among people with disabilities and yields a total Health Practices score plus 4 subscales scores regarding Exercise, Nutrition, Health Practices, and Psychological Well Being. Items are rated on a 5-point scale from 0 'not at all' to 4 'completely.' Scores range from 0-28 with higher scores indicating higher exercise self-efficacy. | Baseline and 12 months |
| Neighborhood walkability using Walk Score® | Walk Score® is publicly available and measures the walkability of any address using a patented system. For each address, Walk Score ® analyzes hundreds of walking routes to nearby amenities and awards points based on distance to each amenity. Walk Score® also measures pedestrian friendliness by analyzing population density and road metrics such a block length and intersection density. Scores are given on a scale of 0 to 100. | Baseline |
| Resting Metabolic Rate | MedGem® is an FDA cleared and validated indirect calorimetry device. It is handheld and measures oxygen consumption (V02) to determine resting metabolic rate (RMR). | Baseline |
| Behavioral Risk Factor Surveillance | The BRFSS is a state-based system of health surveys that collects information on health risk behaviors, preventative health practices, and health care access primarily related to chronic disease and injury. The GLB-TBI uses the two subscales of Healthy Eating and Physical Activity from the 2017 version of the BRFSS. It consists of 14 items. | Baseline, 3, 6, 12 months |
| Participant quality of ife | Quality of life will be assess using the stroke impact scale (SIS), which assesses 8 dimensions of health-related QOL specific to people post CVA including subscales (using a 5pt Likert scale) assessing strength, memory and thinking, emotion, communication, activities of daily living, mobility, hand function, and participation/role function | Baseline, 6, 12 months |
| Stressful Life Events using the Holmes and Rahe Stress Inventory | This inventory consists of 40 life events and asks the participant to recall if any of the events happened within the previous year (e.g., death of spouse; personal illness; change in sleep). Endorsement of these events are totaled and higher scores indicate a greater amount of stressful life events. Point values for the Holmes and Rahe Stress Inventory were weighted and summed for each individual based on scoring instructions. Individuals who scored 150 points or less were categorized as low susceptibility to a health breakdown in the next two years, 151-300 points were 50% chance of health breakdown, and 301 points or more were 80% chance of health breakdown. | Baseline and 12 months |
| Executive Function and Cognition using the Montreal Cognitive Assessment | The MOCA is a brief, 8-section assessment of various cognitive domains including executive function, memory, language, attention, concentration, orientation, and working memory in neurologic populations.Each item on the MOCA is allocated a set of points adding up to 30. | Baseline, 3, and 12 months |
| Habit Formation | The self-reported habit index (SRHI) measures the self-reported perceptions of habit strength for an identified behavior. It consists of 12 items for each selected behavior and uses a 7-point Likert scale from completely disagree to completely agree. Higher totals represent greater perception of habit strength. The SRHI showed high reliability across four studies with alphas of .89, .92, .89, .94, .95, .94, and .85. | Baseline, 3, and 12 months |
| Stroke Severity | The Modified Rankin Scale (MRS) measures the degree of disability or dependence for daily activities of people who have had a stroke. The MRS is an ordinal scale with six categories ranging from zero (no symptoms) to five (complete physical dependence). A score of six signifies death. | Baseline |
| Pain Interference | The Pain Interference-Short Form is taken from the Patient-Reported Outcomes Measurement Information System (PROMIS). This measure is used to assess adult self-reported consequences of pain and pain consequences (e.g. interference in social, cognitive, emotional, physical and recreational activities). This measure consists of four questions with five response option ranging from one to five. The sum of all responses creates a total raw score. This measure is normed to the US general population. | Baseline, 3, 6, and 12 months |
| Sleep Disturbance | The Sleep Disturbance-Short Form 4a is taken from the Patient-Reported Outcomes Measurement Information System (PROMIS) and used to assess adult sleep disturbance profiles. This measure has four questions, each with five response options ranging in value from one to five. The sum of each response creates a total raw score. The measure is normed to the US general population. | Baseline, 3, 6, 12 months |
| Waist Circumference | Waist circumference will be measured at the umbilicus following ACSM guidelines. A total of three measurements will be taken and an average of the three will be the final measurement used. Measurements will be scored in centimeters. | Baseline, 3, 6, and 12 months |
| HbA1c | Fasting venous sample will be obtained for hemoglobin a1c to assess average blood sugar level over the past 2-3 months. Coordinators are trained phlebotomists. | Baseline, 3, 6, and 12 months |
| Triglycerides | Fasting venous sample will be obtained. Coordinators are trained phlebotomists. | Baseline, 3, 6, 12 months |
| Blood Glucose | Fasting venous sample will be obtained. Coordinators are trained phlebotomists. | Baseline, 3, 6, 12 months |
| Biomarker Analysis | Isrin, Angiogenic factors (VEGF), Total Homocysteine, Lipoprotein-associated phospholipase A2 (Lp-PLA2), ICF-1, Brain derived neurotrophic factor (BDNF), and Tau proteins (total and phosphorylated) will be drawn to assess relationships with outcome variables. | Baseline, 3, and 6 months |
| Stages of Change | A modified version of Prochaska and DiClemente's Stages of Change model will be administered to measure readiness for behavior change. The measure consists of two behaviors (eating and exercise) with five questions each related to a stage of change (precontemplation, contemplation, preparation, action, maintenance). | Baseline, 3, 6, and 12 months |
| Metabolic Score Calculator (MetS) | The metabolic score calculator will be used at all time points to determine the risk for metabolic syndrome. The following variables will be used to determine metabolic risk using the free metabolic risk calculator: gender, race and ethnicity, systolic blood pressure, fasting glucose, triglycerides, high-density lipoprotein (HDL), weight, height, and waist circumference. Scores are calculated are standardized to the general population. | Baseline, 3, 6, and 12 months |
| CRISIS (CoRonavIruS Health Impact Survey) V0.3 Adult Baseline Form | This self-report survey was developed by the National Institute of Mental Health. The full survey consists of 64 questions with an open-ended section at the end to elicit concerns and feedback related to the effects of COVID-19. For this current study, however, only sections on Exposure Status (10 items), Life Changes (15 items), and Emotions/Worries (7 items), and the open-ended question will be asked. Questions are asked over the past two weeks. | Up to 12 months |
| PROMIS Social Isolation Short Form 4a | The Social Isolation Short-Form 4a is taken from the Patient-Reported Outcomes Measurement Information System (PROMIS). This form assesses the perceptions of being avoided, excluded, detached, disconnected from, or unknown by, others. There is no timeframe for the form. The measure is normed to the US population. | Up to 12 months |
| Media Questionnaire | To assess media exposure and fear of media exposure during COVID-19 we have added 6 questions. These are asked over the past two weeks. These questions address time spent watching the television, listening to radio, reading the newspaper, and searching the internet and social media. In addition, a 6th question related to fear is asked using a 5-point Likert scale. | Up to 12 months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Group Lifestyle Balance, Physical Activity, Stroke, Weight-loss, Dietary Behaviors
|
NCT05627869
|
Effects of TTPB vs PIFB on Opioid Consumption in Patients After Cardiac Surgery.
|
The objective of this study is to compare the effects of TTPB vs PIFB on postoperative opioid consumption in patients undergoing open cardiac surgery.
|
Cardiac surgery performed through median sternotomy is associated with significant postoperative pain.Poststernotomy pain leads to decreased patient satisfaction, delirium, cardiovascular complications (hypertension, tachycardia, arrhythmias), hyperglycemia and respiratory complications (bronchial secretion stasis, atelectasis and pneumonia).High-dose opioids can provide good postoperative analgesia for patients undergoing heart surgery. However, opioids have some side effects.The advent of ultrasound-guided regional anaesthesia led to the development of fascial plane chest wall block as transthoracic plane block and pectointercostal fascial block.
|
Comparison of Effects of Transversus Thoracic Muscle Plane Block vs Pecto-intercostal Fascial Block on Postoperative Opioid Consumption in Patients Undergoing Open Cardiac Surgery: A Prospective Randomized Study
|
Pain, Postoperative
|
* Procedure: Transversus thoracic plane block
* Procedure: Pecto intercostal fascial block
|
Inclusion Criteria:~Age between 18 and 75 years.~Patient scheduled to undergo elective on-pump cardiac surgery with sternotomy.~American Society of Anesthesiologists classification of physical status < IV.~Exclusion Criteria:~Emergency surgery.~Off-pump surgery.~Redo surgery.~Ejection fraction less than 35%.~Refusal of the patient.~Known hypersensitivity to LA.~Chronic opioid use or chronic pain patient.~Psychiatric problems or communication difficulties.~Liver insufficiency (defined as a serum bilirubin ≥ 34 μmol/l, albumin ≤ 35 g/dl, INR ≥ 1.7)~Renal insufficiency (defined as a glomerular filtration rate < 44 ml/min).~Obstructive sleep apnea syndrome.~Coexisting hematologic disorders.~Pregnancy or breastfeeding.
|
18 Years
|
75 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome will be total morphine consumption | Total morphine consumption within 24 hours according Visual Analogue Score (VAS) for sternal pain both during rest and with cough (ranging from 0 indicating no pain to 10 indicating extreme pain). A score ≤ 3 was considered acceptable for pain relief. Supplementary rescue analgesia was administered in the form of morphine IV 0.05 mg/kg (at VAS ≥ 4). | 24 hours |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary outcomes will be the first analgesic request time | Is the time to ask for the first postoperative analgesia (morphine), and will be calculated from extubation to patient reporting Visual Analogue Score (VAS) ≥ 4. | 24 hours |
|
TTPB, PIFB
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transversus thoracic muscle plane block<br>TTPB group will receive bilateral ultrasound-guided transversus thoracic muscle plane block using 20 ml of bupivacaine 0.25% for each side. | Procedure: Transversus thoracic plane block<br>* TTPB group will receive bilateral ultrasound-guided transversus thoracic muscle plane block using 20 ml of bupivacaine 0.25% for each side.<br>* Other names: sunnypivacaine;|
| Active Comparator: Pecto-intercostal fascial plane block<br>PIFB group will receive bilateral ultrasound-guided Pecto-intercostal fascial plane block using 20 ml of bupivacaine 0.25% for each side. | Procedure: Pecto intercostal fascial block<br>* PIFB group will receive bilateral ultrasound-guided Pecto-intercostal fascial plane block using 20 ml of bupivacaine 0.25% for each side.<br>* Other names: sunnypivacaine;|
|
Effects of TTPB vs PIFB on Opioid Consumption in Patients After Cardiac Surgery.
Study Overview
=================
Brief Summary
-----------------
The objective of this study is to compare the effects of TTPB vs PIFB on postoperative opioid consumption in patients undergoing open cardiac surgery.
Detailed Description
-----------------
Cardiac surgery performed through median sternotomy is associated with significant postoperative pain.Poststernotomy pain leads to decreased patient satisfaction, delirium, cardiovascular complications (hypertension, tachycardia, arrhythmias), hyperglycemia and respiratory complications (bronchial secretion stasis, atelectasis and pneumonia).High-dose opioids can provide good postoperative analgesia for patients undergoing heart surgery. However, opioids have some side effects.The advent of ultrasound-guided regional anaesthesia led to the development of fascial plane chest wall block as transthoracic plane block and pectointercostal fascial block.
Official Title
-----------------
Comparison of Effects of Transversus Thoracic Muscle Plane Block vs Pecto-intercostal Fascial Block on Postoperative Opioid Consumption in Patients Undergoing Open Cardiac Surgery: A Prospective Randomized Study
Conditions
-----------------
Pain, Postoperative
Intervention / Treatment
-----------------
* Procedure: Transversus thoracic plane block
* Procedure: Pecto intercostal fascial block
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 75 years. Patient scheduled to undergo elective on-pump cardiac surgery with sternotomy. American Society of Anesthesiologists classification of physical status < IV. Exclusion Criteria: Emergency surgery. Off-pump surgery. Redo surgery. Ejection fraction less than 35%. Refusal of the patient. Known hypersensitivity to LA. Chronic opioid use or chronic pain patient. Psychiatric problems or communication difficulties. Liver insufficiency (defined as a serum bilirubin ≥ 34 μmol/l, albumin ≤ 35 g/dl, INR ≥ 1.7) Renal insufficiency (defined as a glomerular filtration rate < 44 ml/min). Obstructive sleep apnea syndrome. Coexisting hematologic disorders. Pregnancy or breastfeeding.
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: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transversus thoracic muscle plane block<br>TTPB group will receive bilateral ultrasound-guided transversus thoracic muscle plane block using 20 ml of bupivacaine 0.25% for each side. | Procedure: Transversus thoracic plane block<br>* TTPB group will receive bilateral ultrasound-guided transversus thoracic muscle plane block using 20 ml of bupivacaine 0.25% for each side.<br>* Other names: sunnypivacaine;|
| Active Comparator: Pecto-intercostal fascial plane block<br>PIFB group will receive bilateral ultrasound-guided Pecto-intercostal fascial plane block using 20 ml of bupivacaine 0.25% for each side. | Procedure: Pecto intercostal fascial block<br>* PIFB group will receive bilateral ultrasound-guided Pecto-intercostal fascial plane block using 20 ml of bupivacaine 0.25% for each side.<br>* Other names: sunnypivacaine;|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome will be total morphine consumption | Total morphine consumption within 24 hours according Visual Analogue Score (VAS) for sternal pain both during rest and with cough (ranging from 0 indicating no pain to 10 indicating extreme pain). A score ≤ 3 was considered acceptable for pain relief. Supplementary rescue analgesia was administered in the form of morphine IV 0.05 mg/kg (at VAS ≥ 4). | 24 hours |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary outcomes will be the first analgesic request time | Is the time to ask for the first postoperative analgesia (morphine), and will be calculated from extubation to patient reporting Visual Analogue Score (VAS) ≥ 4. | 24 hours |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TTPB, PIFB
|
|
NCT00774956
|
Shoulder Training: Muscle Recruitment Patterns and the Effect of an Exercise Program
|
The purpose of this study is to investigate the muscle recruitment pattern and the effect of a 6 week shoulder exercise training program in healthy persons and subjects with shoulder impingement
|
Shoulder Training: Muscle Recruitment Patterns and the Effect of an Exercise Program
|
Shoulder Impingement
|
* Procedure: Exercise training program
* Procedure: Exercise training program
|
Inclusion Criteria:~current reported history of shoulder pain localised at the glenohumeral joint diagnosed as impingement~two positive shoulder impingement tests~pain reproduction during two of three additional categories of clinical tests~the subject is able to perform pain-free arm elevations with a resistance of 0.5 kg~Exclusion Criteria:~cervical and periscapular pain~positive labral injury tests~history of shoulder surgery
|
18 Years
|
40 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 |
| --- | --- | --- |
| Muscle recruitment pattern | | After 6 weeks of training |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shoulder pain and functional ability in the patient group | | After 6 weeks of training |
|
Shoulder Impingement Syndrome, Joint Diseases, Musculoskeletal Diseases, Shoulder Injuries, Wounds and Injuries
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Subject with shoulder impingement | Procedure: Exercise training program<br>* A 6 week shoulder exercise training program<br>|
| Active Comparator: 2<br>Healthy persons | Procedure: Exercise training program<br>* A 6 week shoulder exercise training program<br>|
|
Shoulder Training: Muscle Recruitment Patterns and the Effect of an Exercise Program
Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the muscle recruitment pattern and the effect of a 6 week shoulder exercise training program in healthy persons and subjects with shoulder impingement
Official Title
-----------------
Shoulder Training: Muscle Recruitment Patterns and the Effect of an Exercise Program
Conditions
-----------------
Shoulder Impingement
Intervention / Treatment
-----------------
* Procedure: Exercise training program
* Procedure: Exercise training program
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: current reported history of shoulder pain localised at the glenohumeral joint diagnosed as impingement two positive shoulder impingement tests pain reproduction during two of three additional categories of clinical tests the subject is able to perform pain-free arm elevations with a resistance of 0.5 kg Exclusion Criteria: cervical and periscapular pain positive labral injury tests history of shoulder surgery
Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 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: 1<br>Subject with shoulder impingement | Procedure: Exercise training program<br>* A 6 week shoulder exercise training program<br>|
| Active Comparator: 2<br>Healthy persons | Procedure: Exercise training program<br>* A 6 week shoulder exercise training program<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle recruitment pattern | | After 6 weeks of training |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shoulder pain and functional ability in the patient group | | After 6 weeks of training |
|
||
NCT03388970
|
Vitamin K1 in the Treatment of Spontaneous Intracerebral Hemorrhage
|
In order to determine the effectiveness and safety of early vitamin K1 use in reducing the risk of bleeding and improving prognosis in patients with spontaneous intracerebral hemorrhage. Patients with spontaneous intracerebral hemorrhage (excluding rupture of aneurysm and vascular malformation) will be randomly divided into experimental group and control group. All the patients in the two groups were treated according to the guideline of spontaneous intracerebral hemorrhage. Patients in the experimental group was treated with intravenous injection of vitamin K1 20mg once a day for 2 days after admission, and the patients in control group was treated with normal saline as a control. The hematoma volume, coagulation function, platelet levels and GCS scales of the two groups will be recorded in 0d, 1d, 3d, 7d post bleeding stroke, furthermore, length of ICU stay and total hospitalization, incidence of complications during hospitalization are to be recorded. During the follow-up, mRS score will be recorded at 1m and 6m post bleeding stroke.
|
Spontaneous intracerebral hemorrhage is a common disease in the department of neurosurgery, which often leads to long-term coma and severe neurological dysfunction. The amount of cerebral hemorrhage is directly related to the prognosis of the patients, and a small number of patients still suffer from the adverse consequences of delayed bleeding after active treatment. Vitamin K1 is a necessary ingredient in the liver to produce clotting factors II, VII, IX, and X, and vitamin K1 supplementation increases clotting function. On the contrary, vitamin K1 increases the risk of thrombosis. In this study, patients with spontaneous intracerebral hemorrhage (excluding rupture of aneurysm and vascular malformation) will be randomly divided into experimental group and control group. All the patients in the two groups were treated according to the guideline of spontaneous intracerebral hemorrhage. Patients in the experimental group was treated with intravenous injection of vitamin K1 20mg once a day for 2 days after admission, and the patients in control group was treated with normal saline as a control. The hematoma volume, coagulation function, platelet levels and GCS scales of the two groups will be recorded in 0d, 1d, 3d, 7d post bleeding stroke, furthermore, length of ICU stay and total hospitalization, incidence of complications during hospitalization are to be recorded. During the follow-up, mRS score will be recorded at 1m and 6m post bleeding stroke. Finally, the effectiveness and safety of early vitamin K1 use in reducing the risk of bleeding and improving prognosis in patients with spontaneous intracerebral hemorrhage will be analyzed.
|
Multicenter Randomized Controlled Trial of Vitamin K1 in the Treatment of Spontaneous Intracerebral Hemorrhage
|
Intracerebral Haemorrhage in Cerebellum
|
* Drug: Vitamin K 1
* Drug: normal saline
|
Inclusion Criteria:~Spontaneous intracerebral hemorrhage (Non - aneurysmal or arteriovenous malformations which confirmed by cerebral arterial CT enhancement or DSA);~Age 18-65 years, male or non-pregnant female;~GCS score at admission (4 to12);~during the hospitalization, no urokinase and other hemostatic drugs were used except for etamsylate and vitamin K1;~informed consent signed by the patient's family~Exclusion Criteria:~irregular lobulated hematoma (volume of hematoma can not be calculated accurately), such as intraventricular hemorrhage;~severe liver disease or impaired liver function;~pregnant or lactating women;~history of using anticoagulation or antiplatelet aggregation drug (including Cilostazol, aspirin, dipyridamole, heparin, low molecular weight heparin, hirudin, dabigatran, and warfarin);~non-accepted informed consent
|
18 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The volume of cerebral hemorrhage | The volume of cerebral hemorrhage at certain time post onset（ml） | Day0 |
| The volume of cerebral hemorrhage | The volume of cerebral hemorrhage at certain time post onset（ml） | Day3 |
| The volume of cerebral hemorrhage | The volume of cerebral hemorrhage at certain time post onset（ml） | Day7 |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Activated Partial Thromboplastin Time（s）at certain time post onset | Activated Partial Thromboplastin Time（s） | Day0 |
| The Activated Partial Thromboplastin Time（s）at certain time post onset | Activated Partial Thromboplastin Time（s） | Day3 |
| The Activated Partial Thromboplastin Time（s）at certain time post onset | Activated Partial Thromboplastin Time（s） | Day7 |
| The condition of Platelet level at certain time post onset | The condition of Platelet level at certain time post onset（10^9/L） | Day0 |
| The condition of Platelet level at certain time post onset | The condition of Platelet level at certain time post onset（10^9/L） | Day3 |
| The condition of Platelet level at certain time post onset | The condition of Platelet level at certain time post onset（10^9/L） | Day7 |
| The condition of GCS scale post(3-15) at certain time post onset | The condition of GCS scale post(3-15) at certain time post onset | Day0 |
| The condition of GCS scale post(3-15) at certain time post onset | The condition of GCS scale post(3-15) at certain time post onset | Day3 |
| The condition of GCS scale post(3-15) at certain time post onset | The condition of GCS scale post(3-15) at certain time post onset | Day7 |
| The prothrombin time(s) at certain time post onset | prothrombin time(s) | Day0 |
| The prothrombin time(s) at certain time post onset | prothrombin time(s) | Day3 |
| The prothrombin time(s) at certain time post onset | prothrombin time(s) | Day7 |
| The Fibrinogen (g/L)at certain time post onset | Fibrinogen (g/L) | Day0 |
| The Fibrinogen (g/L)at certain time post onset | Fibrinogen (g/L) | Day3 |
| The Fibrinogen (g/L)at certain time post onset | Fibrinogen (g/L) | Day7 |
| The Thrombin Time(s) at certain time post onset | Thrombin Time(s) | Day0 |
| The Thrombin Time(s) at certain time post onset | Thrombin Time(s) | Day3 |
| The Thrombin Time(s) at certain time post onset | Thrombin Time(s) | Day7 |
|
vitamin K1, spontaneous intracerebral hemorrhage, effectiveness, outcome
|
Vitamin K, Vitamin K 1, Vitamins, Micronutrients, Physiological Effects of Drugs, Antifibrinolytic Agents, Fibrin Modulating Agents, Molecular Mechanisms of Pharmacological Action, Hemostatics, Coagulants
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: research group<br>normal saline 100ml+ vitamin K1 20mg ivgtt qd day0 and day1。 | Drug: Vitamin K 1<br>* Research group use Vitamin K1<br>|
| Placebo Comparator: placebo group<br>normal saline100ml + normal saline 2 ml ivgtt qd day0 and day1 | Drug: normal saline<br>* Placebo group use normal saline<br>|
|
Vitamin K1 in the Treatment of Spontaneous Intracerebral Hemorrhage
Study Overview
=================
Brief Summary
-----------------
In order to determine the effectiveness and safety of early vitamin K1 use in reducing the risk of bleeding and improving prognosis in patients with spontaneous intracerebral hemorrhage. Patients with spontaneous intracerebral hemorrhage (excluding rupture of aneurysm and vascular malformation) will be randomly divided into experimental group and control group. All the patients in the two groups were treated according to the guideline of spontaneous intracerebral hemorrhage. Patients in the experimental group was treated with intravenous injection of vitamin K1 20mg once a day for 2 days after admission, and the patients in control group was treated with normal saline as a control. The hematoma volume, coagulation function, platelet levels and GCS scales of the two groups will be recorded in 0d, 1d, 3d, 7d post bleeding stroke, furthermore, length of ICU stay and total hospitalization, incidence of complications during hospitalization are to be recorded. During the follow-up, mRS score will be recorded at 1m and 6m post bleeding stroke.
Detailed Description
-----------------
Spontaneous intracerebral hemorrhage is a common disease in the department of neurosurgery, which often leads to long-term coma and severe neurological dysfunction. The amount of cerebral hemorrhage is directly related to the prognosis of the patients, and a small number of patients still suffer from the adverse consequences of delayed bleeding after active treatment. Vitamin K1 is a necessary ingredient in the liver to produce clotting factors II, VII, IX, and X, and vitamin K1 supplementation increases clotting function. On the contrary, vitamin K1 increases the risk of thrombosis. In this study, patients with spontaneous intracerebral hemorrhage (excluding rupture of aneurysm and vascular malformation) will be randomly divided into experimental group and control group. All the patients in the two groups were treated according to the guideline of spontaneous intracerebral hemorrhage. Patients in the experimental group was treated with intravenous injection of vitamin K1 20mg once a day for 2 days after admission, and the patients in control group was treated with normal saline as a control. The hematoma volume, coagulation function, platelet levels and GCS scales of the two groups will be recorded in 0d, 1d, 3d, 7d post bleeding stroke, furthermore, length of ICU stay and total hospitalization, incidence of complications during hospitalization are to be recorded. During the follow-up, mRS score will be recorded at 1m and 6m post bleeding stroke. Finally, the effectiveness and safety of early vitamin K1 use in reducing the risk of bleeding and improving prognosis in patients with spontaneous intracerebral hemorrhage will be analyzed.
Official Title
-----------------
Multicenter Randomized Controlled Trial of Vitamin K1 in the Treatment of Spontaneous Intracerebral Hemorrhage
Conditions
-----------------
Intracerebral Haemorrhage in Cerebellum
Intervention / Treatment
-----------------
* Drug: Vitamin K 1
* Drug: normal saline
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Spontaneous intracerebral hemorrhage (Non - aneurysmal or arteriovenous malformations which confirmed by cerebral arterial CT enhancement or DSA); Age 18-65 years, male or non-pregnant female; GCS score at admission (4 to12); during the hospitalization, no urokinase and other hemostatic drugs were used except for etamsylate and vitamin K1; informed consent signed by the patient's family Exclusion Criteria: irregular lobulated hematoma (volume of hematoma can not be calculated accurately), such as intraventricular hemorrhage; severe liver disease or impaired liver function; pregnant or lactating women; history of using anticoagulation or antiplatelet aggregation drug (including Cilostazol, aspirin, dipyridamole, heparin, low molecular weight heparin, hirudin, dabigatran, and warfarin); non-accepted 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: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: research group<br>normal saline 100ml+ vitamin K1 20mg ivgtt qd day0 and day1。 | Drug: Vitamin K 1<br>* Research group use Vitamin K1<br>|
| Placebo Comparator: placebo group<br>normal saline100ml + normal saline 2 ml ivgtt qd day0 and day1 | Drug: normal saline<br>* Placebo group use normal saline<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The volume of cerebral hemorrhage | The volume of cerebral hemorrhage at certain time post onset（ml） | Day0 |
| The volume of cerebral hemorrhage | The volume of cerebral hemorrhage at certain time post onset（ml） | Day3 |
| The volume of cerebral hemorrhage | The volume of cerebral hemorrhage at certain time post onset（ml） | Day7 |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Activated Partial Thromboplastin Time（s）at certain time post onset | Activated Partial Thromboplastin Time（s） | Day0 |
| The Activated Partial Thromboplastin Time（s）at certain time post onset | Activated Partial Thromboplastin Time（s） | Day3 |
| The Activated Partial Thromboplastin Time（s）at certain time post onset | Activated Partial Thromboplastin Time（s） | Day7 |
| The condition of Platelet level at certain time post onset | The condition of Platelet level at certain time post onset（10^9/L） | Day0 |
| The condition of Platelet level at certain time post onset | The condition of Platelet level at certain time post onset（10^9/L） | Day3 |
| The condition of Platelet level at certain time post onset | The condition of Platelet level at certain time post onset（10^9/L） | Day7 |
| The condition of GCS scale post(3-15) at certain time post onset | The condition of GCS scale post(3-15) at certain time post onset | Day0 |
| The condition of GCS scale post(3-15) at certain time post onset | The condition of GCS scale post(3-15) at certain time post onset | Day3 |
| The condition of GCS scale post(3-15) at certain time post onset | The condition of GCS scale post(3-15) at certain time post onset | Day7 |
| The prothrombin time(s) at certain time post onset | prothrombin time(s) | Day0 |
| The prothrombin time(s) at certain time post onset | prothrombin time(s) | Day3 |
| The prothrombin time(s) at certain time post onset | prothrombin time(s) | Day7 |
| The Fibrinogen (g/L)at certain time post onset | Fibrinogen (g/L) | Day0 |
| The Fibrinogen (g/L)at certain time post onset | Fibrinogen (g/L) | Day3 |
| The Fibrinogen (g/L)at certain time post onset | Fibrinogen (g/L) | Day7 |
| The Thrombin Time(s) at certain time post onset | Thrombin Time(s) | Day0 |
| The Thrombin Time(s) at certain time post onset | Thrombin Time(s) | Day3 |
| The Thrombin Time(s) at certain time post onset | Thrombin Time(s) | Day7 |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vitamin K1, spontaneous intracerebral hemorrhage, effectiveness, outcome
|
NCT05018832
|
Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cell Intravenous Infusion for TBI
|
This trial will study the safety and efficacy of intravenous infusion of cultured allogeneic adult umbilical cord derived mesenchymal stem cells for the treatment of traumatic brain injury
|
Studies have shown that stem cell treatment is safe and efficacious for the treatment of Traumatic brain injury (TBI). This patient funded trial aims to study the safety and efficacy of intravenous infusion of cultured allogeneic adult umbilical cord derived mesenchymal stem cells (UC-MSCs) for the treatment of TBI. Patients with TBI will receive a single intravenous infusion of UC-MSCs. The total dose will be 100 million cells. Patients will be evaluated within one month pre treatment and at 1, 6, 12, 24, 36, and 48 months post treatment for safety and efficacy.
|
Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cell Intravenous Infusion for the Treatment of Traumatic Brain Injury
|
Traumatic Brain Injury
|
* Biological: AlloRx
|
Inclusion Criteria:~Diagnosis of traumatic brain injury~Understanding and willingness to sign a written informed consent document~Exclusion Criteria:~Active infection~Active cancer~Chronic multisystem organ failure~Pregnancy~Clinically significant Abnormalities on pre-treatment laboratory evaluation~Medical condition that would (based on the opinion of the investigator) compromise patient's safety.~Continued drug abuse~Pre-menopausal women not using contraception~Previous organ transplant~Hypersensitivity to sulfur~Seizure disorders
| null | null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (adverse events) | Clinical monitoring of possible adverse events or complications | Four year follow-up |
|
Traumatic brain injury, stem cell treatment
|
Brain Injuries, Brain Injuries, Traumatic, Wounds and Injuries, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Craniocerebral Trauma, Trauma, Nervous System
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group (AlloRx)<br>Single intravenous infusion of 100 million cells | Biological: AlloRx<br>* cultured allogeneic adult umbilical cord derived mesenchymal stem cells<br>|
|
Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cell Intravenous Infusion for TBI
Study Overview
=================
Brief Summary
-----------------
This trial will study the safety and efficacy of intravenous infusion of cultured allogeneic adult umbilical cord derived mesenchymal stem cells for the treatment of traumatic brain injury
Detailed Description
-----------------
Studies have shown that stem cell treatment is safe and efficacious for the treatment of Traumatic brain injury (TBI). This patient funded trial aims to study the safety and efficacy of intravenous infusion of cultured allogeneic adult umbilical cord derived mesenchymal stem cells (UC-MSCs) for the treatment of TBI. Patients with TBI will receive a single intravenous infusion of UC-MSCs. The total dose will be 100 million cells. Patients will be evaluated within one month pre treatment and at 1, 6, 12, 24, 36, and 48 months post treatment for safety and efficacy.
Official Title
-----------------
Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cell Intravenous Infusion for the Treatment of Traumatic Brain Injury
Conditions
-----------------
Traumatic Brain Injury
Intervention / Treatment
-----------------
* Biological: AlloRx
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of traumatic brain injury Understanding and willingness to sign a written informed consent document Exclusion Criteria: Active infection Active cancer Chronic multisystem organ failure Pregnancy Clinically significant Abnormalities on pre-treatment laboratory evaluation Medical condition that would (based on the opinion of the investigator) compromise patient's safety. Continued drug abuse Pre-menopausal women not using contraception Previous organ transplant Hypersensitivity to sulfur Seizure disorders
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 Group (AlloRx)<br>Single intravenous infusion of 100 million cells | Biological: AlloRx<br>* cultured allogeneic adult umbilical cord derived mesenchymal stem cells<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (adverse events) | Clinical monitoring of possible adverse events or complications | Four year follow-up |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Traumatic brain injury, stem cell treatment
|
|
NCT01384279
|
The Therapeutic Effects of Topiramate and Metformin on Second Generation Antipsychotics-induced Obesity
|
The primary aim of the study is to investigate the efficacy of metformin and topiramate on second-generation antipsychotic-induced obesity. The secondary domain we look at is the adverse effects of both drugs. The investigators hypothesize that metformin and topiramate are effective in treating obesity induced by second-generation antipsychotics.
|
The Therapeutic Effects of Topiramate and Metformin on Second Generation Antipsychotics-induced Obesity
|
Obesity
|
* Drug: metformin, topiramate
|
Inclusion Criteria:~Diagnosis: schizophrenia or schizoaffective disorder~Age: 20 to 65~BMI>27~Receiving second-generation antipsychotics(Olanzapine, Clozapine, Quetiapine, Risperidone, Amisulpride, Zotepine)~Exclusion Criteria:~Allergy to metformin or topiramate~Currently taking metformin or topiramate~Currently taking drugs that may interact with topiramate, including carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, amitriptyline, lithium, metformin, propranolol, and sumatriptan.~Being pregnant or planning to become pregnant during the study period,~History of hypertension, DM, liver or renal function impairment, cardiovascular disease, CVA, or neurological disorders~History of hypoglycemia~History of suicidal attempt~Current scale of Hamilton Depression Rating Scale>8
|
20 Years
|
65 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes in metabolic panel as the primary outcome | Metabolic panel, which includes HDL-C, VLDL, LDL, cholesterol, triglycerides, insulin, leptin, BW, Glucose, blood pressure, and weight(with waist circumference and BMI) will be assessed every month | up to six months |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (including psychiatric adverse events) as a Measure of Safety and Tolerability | We use Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale, clinical golbal impression-severity, and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale every month to investigate the participants' safety and tolerability. | up to six months |
|
metformin, topiramate, obesity, metabolic syndrome
|
Metformin, Topiramate, Hypoglycemic Agents, Physiological Effects of Drugs, Anticonvulsants
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: metformin, topiramate<br> | Drug: metformin, topiramate<br>* metformin 250 mg/d is gradually increased to 1000 mg/d over four weeks, and topiramate 50 mg/d is gradually increased to 200 mg/d over four weeks<br>|
|
The Therapeutic Effects of Topiramate and Metformin on Second Generation Antipsychotics-induced Obesity
Study Overview
=================
Brief Summary
-----------------
The primary aim of the study is to investigate the efficacy of metformin and topiramate on second-generation antipsychotic-induced obesity. The secondary domain we look at is the adverse effects of both drugs. The investigators hypothesize that metformin and topiramate are effective in treating obesity induced by second-generation antipsychotics.
Official Title
-----------------
The Therapeutic Effects of Topiramate and Metformin on Second Generation Antipsychotics-induced Obesity
Conditions
-----------------
Obesity
Intervention / Treatment
-----------------
* Drug: metformin, topiramate
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis: schizophrenia or schizoaffective disorder Age: 20 to 65 BMI>27 Receiving second-generation antipsychotics(Olanzapine, Clozapine, Quetiapine, Risperidone, Amisulpride, Zotepine) Exclusion Criteria: Allergy to metformin or topiramate Currently taking metformin or topiramate Currently taking drugs that may interact with topiramate, including carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, amitriptyline, lithium, metformin, propranolol, and sumatriptan. Being pregnant or planning to become pregnant during the study period, History of hypertension, DM, liver or renal function impairment, cardiovascular disease, CVA, or neurological disorders History of hypoglycemia History of suicidal attempt Current scale of Hamilton Depression Rating Scale>8
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: metformin, topiramate<br> | Drug: metformin, topiramate<br>* metformin 250 mg/d is gradually increased to 1000 mg/d over four weeks, and topiramate 50 mg/d is gradually increased to 200 mg/d over four weeks<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes in metabolic panel as the primary outcome | Metabolic panel, which includes HDL-C, VLDL, LDL, cholesterol, triglycerides, insulin, leptin, BW, Glucose, blood pressure, and weight(with waist circumference and BMI) will be assessed every month | up to six months |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (including psychiatric adverse events) as a Measure of Safety and Tolerability | We use Positive and Negative Syndrome Scale, the Hamilton Depression Rating Scale, clinical golbal impression-severity, and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale every month to investigate the participants' safety and tolerability. | up to six months |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
metformin, topiramate, obesity, metabolic syndrome
|
|
NCT05140486
|
Targeted Shortwave Diathermy Combined With Perceptual Training for Patients With Severe Traumatic Optic Neuropathy
|
Purpose: Patients with severe traumatic optic neuropathy (TON) have limited improvement in visual function despite therapy. The hypothesis of the study is that the targeted shortwave diathermy combined with perceptual training may enhance visual function in patients with severe TON after endoscopic optic nerve decompression (EOND) surgery.~Design: Clinical trial Subjects: Twenty-two subjects with severe TON after EOND surgery were randomly assigned to either a rehabilitation (Reh) group or nonrehabilitation (Nreh) group.~Methods: High-resolution computed tomography and MRI were used to locate the impaired nerve. The subjects in the Reh group received targeted shortwave diathermy therapy 5 days per week for 4 weeks and perceptual training 5 days per week for 10 weeks.~Main Outcome Measures: A thorough evaluation of visual function, visual evoked potential, and diffusion tensor imaging was executed.
|
Study sample description Indirect traumatic optic neuropathy (TON) was diagnosed by a history of blunt head or facial trauma combined with decreased visual acuity, color vision and a relative afferent pupillary defect with a normal fundus during the early period of post-trauma. The investigators excluded cases with direct trauma to optic nerve identified by high-resolution CT scan of the orbital and optic canal. The patients with indirect TON were intravenously administered methylprednisolone (30 mg/kg per day) every day for three consecutive days. All consecutive subjects with indirect TON who were admitted to Xiangya Hospital and managed with endoscopic optic nerve decompression surgery were recruited. The subjects were randomly assigned to either a rehabilitation group or a nonrehabilitation group. Since there were no grading criteria in evaluating the severity of indirect TON, TON with Best-corrected visual acuity equal to or more than 1.85 LogMAR after endoscopic optic nerve decompression surgery was considered severe TON and those patients were recruited in this study. The subjects in the rehabilitation group will receive shortwave diathermy therapy and perceptual training after endoscopic optic nerve decompression surgery. The subjects in the nonrehabilitation group will not receive any rehabilitation treatment after endoscopic optic nerve decompression surgery.~Endoscopic ON decompression surgery All operations were performed under general anesthesia by a surgeon (Hua Zhang). Briefly, a routine endoscopic endonasal sphenoethmoidectomy was performed to expose and resect the posterior ethmoidal lamina papyracea. After the optic canal was exposed, the upper, medial and partial lower surfaces of the whole range of the optic canal wall were removed. Finally, the ON sheath from the annulus of the Zinn to the cranial cavity, along with the annulus of the Zinn, was incised, and the surface of the ON was covered with a piece of gelatin sponge filled with methylprednisolone solution (40 mg/mL).~Shortwave diathermy therapy The Shortwave diathermy (SWD) device applied in this study was DL-CⅡ (Dajia®, Shantou, China). This therapeutic apparatus delivered at a frequency of approximately 27.12±0.6% MHz in continuous modes with a power of 50 W±20%. In our study, two sets of circular capacitive electrodes were used with a diameter of 80 mm for adults and 50 mm for children. The fracture areas were located using high-resolution CT scan. One electrode was applied in the temporal area of the ipsilateral side of the injured nerve identified by a three-dimensional alignment procedure through high-resolution CT scan. This area was not only shorter distance from the skin to the injured nerve but was also as far away from the crystalline lens as possible. To decrease the negative effects of SWD on the nerve systems, another circular electrode of SWD was applied in the frontal area of the ipsilateral side of the injured nerve. In the acute stage of the TON (within 10 days after injury), the athermal mode of the SWD was applied to the marked areas for a 10-minute daily session. Ten days after injury, the microthermal mode was used for a 15-minute daily session. All subjects in the rehabilitation group received SWD therapy 5 days per week for 4 wks.~Perceptual training Perceptive learning sessions were composed of a series of training procedures. First, sensory stimulations including touch, stroking, tapping and pressing on the local area of the ipsilateral eye as well as surface location of the injured ON were offered. Second, light stimulation was applied at different intensities of bright based on evaluation of the pupillary light reflex of the subject, 1 to 5 seconds each time, 10 to 15 times a day, and avoiding glare and longtime light stimulation on eye when training. Additionally, the subjects were instructed to enter the bright room from the dark room when the participants were wearing an eye patch in the intact eye. Third, differentiation of the shapes and objects in dynamic or static states with different colors, different sizes and different shapes was performed. Either real objects or pictures could be selected in the training session. Fourth, different written words with different sizes and different distances were discriminated in the different directions of the eye. Based on evaluation of the visual acuity, the training sequence was from large words to small, from simple words to complex, and from proximal to distal distance of the eye. Fifth, color vision was trained using real objects or pictures. The subjects were instructed to select the color from the single and bright to multiple and dark color. The color contrast was initiated from maximum to minimal contrast. Finally, the visual field training was scattered in the above training methods. Each training media including the light, objects, words and color was input from the anterior, superior, inferior, nasal and temporal sides of the eye. These trainings started from the center of the normal visual field to the terminal of the visual field. When the training media reached the terminal of the visual field in every direction, ocular fixation with 2-5 seconds was performed to increase the scope of the visual field. Each stimulation was given 5-10 times for each direction. In the early periods of the training, when the visual acuity was complete loss, the training sections were relatively independent. When the visual acuity of subjects was partially recovered, the training sections were mixed. In addition, many training techniques were used in this study. First, visual imagery training was used when the patients had complete or severe visual loss. Visual imagery training can be defined as a dynamic state during which the representation of a specific object is internally reactivated within visual memory without any overt visual input and that is governed by the principles of central visual control. The intervention of the VI training was as follows: the subjects used the intact eye to observe the object for 5 seconds, then the participants closed their eyes and imagined viewing the object using the injured eye for 10 seconds for 10 repetitions. Additionally, proprioceptive training, including going over the barriers, going up and downstairs, walking the slope, and training the balance, was executed. Finally, constraint-induced perceptive therapy was performed when the visual lesion partially recovered. The subjects wore an eye patch on the intact eye for 30 minutes in one section, 2 to 4 hours a day, 7 days per week. In constraint-induced perceptive training, activities of daily living (ADL), natural environmental training and fun games with colorful objects were executed, and the subjects were instructed to complete the ADL, play gobang, watch the green leaves and colorful flowers from proximal to distal distance. All the subjects in the Reh group received perceptive learning therapy 5 days per week for 10 weeks except constraint-induced perceptive therapy.
|
Targeted Shortwave Diathermy Combined With Perceptual Training for Patients With Severe Traumatic Optic Neuropathy After Endoscopic Optic Nerve Decompression: a Preliminary Clinical Trial.
|
Traumatic Optic Neuropathy
|
* Procedure: Rehabilitation: shortwave diathermy and perceptual training
|
Inclusion criteria:~The indications for endoscopic optic nerve decompression surgery included no improvement after intravenous treatment for 24 hours, no evidence of injury in the intracranial portion of the optic nerve, and the presence of bony fragments or hematoma compressing the optic nerve.~TON with best-corrected visual acuity equal to or more than 1.85 logMAR after surgery was considered as severe TON, and those patients managed with endoscopic optic nerve decompression surgery were recruited in this study.~Eligible criteria for the participants were as follows: (1) not receiving other physical therapy regimens aside from this intervention; (2) age 3 to 60 years old; (3) ability to execute simple verbal instructions; (4) not being delirious; (5) having stable vital signs and medical conditions.~Exclusion criteria:~The exclusion criteria included severe diffuse brain damage, and/or severe cardiac and pulmonary disease, which were contraindicated in rehabilitation procedure.
|
3 Years
|
60 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI | A 32-channel head coil on a 3.0T MRI system (Philips, Ltd, Best, the Netherlands) was used for the acquisition of imaging data. T1- and T2-weighted, fat-suppressed images were obtained axially through the orbit and some parts of the brain, including the intracranial portion of the optic nerve, postoperatively and 10 weeks after rehabilitation. | 15 minutes |
| Diffusion tensor imaging | Optic nerve diffusion tensor imaging images were obtained using single-shot echoplanar imaging sequences. The images were acquired from the optic papilla to the orbital apex of the optic nerve with 40 contiguous slices. The region of interest was manually manually placed over the optic nerve at the anterior, middle, and posterior segments on the non-diffusion-weighted image. The fraction anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of optic nerves were measured. | 15 minutes |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual evoked potential | Pattern visual evoked potential testing was recorded using an MEB-9404C (Nihon Kohden Corp, Tokyo, Japan). The latency and amplitude of the P100 wave in the VEP testing were collected for analysis. | 30 minutes |
| Best-corrected visual acuity | Best-corrected visual acuity was measured by a standardized Snellen visual chart. Visual results were converted into logMAR units for the convenience of statistical analysis. Hand motion, light perception, and no light perception were converted to 2.3, 2.5, and 3 logMAR units, respectively. | 5 minutes |
| Color vision | Color vision was evaluated using the Ishihara color vision test 24 plate. The exclusion criterion of the color vision test was congenital color vision deficiency. The number of correct answers in a set of 24 plates was recorded as the color vision score. | 5 minutes |
|
Shortwave diathermy, perceptual training, traumatic optic neuropathy
|
Peripheral Nervous System Diseases, Optic Nerve Diseases, Optic Nerve Injuries, Hyperthermia, Neuromuscular Diseases, Nervous System Diseases, Cranial Nerve Diseases, Eye Diseases, Body Temperature Changes, Heat Stress Disorders, Wounds and Injuries, Cranial Nerve Injuries, Craniocerebral Trauma, Trauma, Nervous System
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Shortwave diathermy and perceptual training<br>The subjects in this group will receive shortwave diathermy 5 days per week for 4 weeks and perceptual training 5 days per week for 10 weeks after endoscopic optic nerve decompression surgery. | Procedure: Rehabilitation: shortwave diathermy and perceptual training<br>* All subjects in the rehabilitation group received shortwave diathermy therapy 5 days per week for 4 weeks and perceptual training 5 days per week for 10 weeks.<br>|
| No Intervention: Nonrehabilitation<br>The subjects in the nonrehabilitation group will not only receive any rehabilitation therapy after endoscopic optic nerve decompression surgery. | |
|
Targeted Shortwave Diathermy Combined With Perceptual Training for Patients With Severe Traumatic Optic Neuropathy
Study Overview
=================
Brief Summary
-----------------
Purpose: Patients with severe traumatic optic neuropathy (TON) have limited improvement in visual function despite therapy. The hypothesis of the study is that the targeted shortwave diathermy combined with perceptual training may enhance visual function in patients with severe TON after endoscopic optic nerve decompression (EOND) surgery. Design: Clinical trial Subjects: Twenty-two subjects with severe TON after EOND surgery were randomly assigned to either a rehabilitation (Reh) group or nonrehabilitation (Nreh) group. Methods: High-resolution computed tomography and MRI were used to locate the impaired nerve. The subjects in the Reh group received targeted shortwave diathermy therapy 5 days per week for 4 weeks and perceptual training 5 days per week for 10 weeks. Main Outcome Measures: A thorough evaluation of visual function, visual evoked potential, and diffusion tensor imaging was executed.
Detailed Description
-----------------
Study sample description Indirect traumatic optic neuropathy (TON) was diagnosed by a history of blunt head or facial trauma combined with decreased visual acuity, color vision and a relative afferent pupillary defect with a normal fundus during the early period of post-trauma. The investigators excluded cases with direct trauma to optic nerve identified by high-resolution CT scan of the orbital and optic canal. The patients with indirect TON were intravenously administered methylprednisolone (30 mg/kg per day) every day for three consecutive days. All consecutive subjects with indirect TON who were admitted to Xiangya Hospital and managed with endoscopic optic nerve decompression surgery were recruited. The subjects were randomly assigned to either a rehabilitation group or a nonrehabilitation group. Since there were no grading criteria in evaluating the severity of indirect TON, TON with Best-corrected visual acuity equal to or more than 1.85 LogMAR after endoscopic optic nerve decompression surgery was considered severe TON and those patients were recruited in this study. The subjects in the rehabilitation group will receive shortwave diathermy therapy and perceptual training after endoscopic optic nerve decompression surgery. The subjects in the nonrehabilitation group will not receive any rehabilitation treatment after endoscopic optic nerve decompression surgery. Endoscopic ON decompression surgery All operations were performed under general anesthesia by a surgeon (Hua Zhang). Briefly, a routine endoscopic endonasal sphenoethmoidectomy was performed to expose and resect the posterior ethmoidal lamina papyracea. After the optic canal was exposed, the upper, medial and partial lower surfaces of the whole range of the optic canal wall were removed. Finally, the ON sheath from the annulus of the Zinn to the cranial cavity, along with the annulus of the Zinn, was incised, and the surface of the ON was covered with a piece of gelatin sponge filled with methylprednisolone solution (40 mg/mL). Shortwave diathermy therapy The Shortwave diathermy (SWD) device applied in this study was DL-CⅡ (Dajia®, Shantou, China). This therapeutic apparatus delivered at a frequency of approximately 27.12±0.6% MHz in continuous modes with a power of 50 W±20%. In our study, two sets of circular capacitive electrodes were used with a diameter of 80 mm for adults and 50 mm for children. The fracture areas were located using high-resolution CT scan. One electrode was applied in the temporal area of the ipsilateral side of the injured nerve identified by a three-dimensional alignment procedure through high-resolution CT scan. This area was not only shorter distance from the skin to the injured nerve but was also as far away from the crystalline lens as possible. To decrease the negative effects of SWD on the nerve systems, another circular electrode of SWD was applied in the frontal area of the ipsilateral side of the injured nerve. In the acute stage of the TON (within 10 days after injury), the athermal mode of the SWD was applied to the marked areas for a 10-minute daily session. Ten days after injury, the microthermal mode was used for a 15-minute daily session. All subjects in the rehabilitation group received SWD therapy 5 days per week for 4 wks. Perceptual training Perceptive learning sessions were composed of a series of training procedures. First, sensory stimulations including touch, stroking, tapping and pressing on the local area of the ipsilateral eye as well as surface location of the injured ON were offered. Second, light stimulation was applied at different intensities of bright based on evaluation of the pupillary light reflex of the subject, 1 to 5 seconds each time, 10 to 15 times a day, and avoiding glare and longtime light stimulation on eye when training. Additionally, the subjects were instructed to enter the bright room from the dark room when the participants were wearing an eye patch in the intact eye. Third, differentiation of the shapes and objects in dynamic or static states with different colors, different sizes and different shapes was performed. Either real objects or pictures could be selected in the training session. Fourth, different written words with different sizes and different distances were discriminated in the different directions of the eye. Based on evaluation of the visual acuity, the training sequence was from large words to small, from simple words to complex, and from proximal to distal distance of the eye. Fifth, color vision was trained using real objects or pictures. The subjects were instructed to select the color from the single and bright to multiple and dark color. The color contrast was initiated from maximum to minimal contrast. Finally, the visual field training was scattered in the above training methods. Each training media including the light, objects, words and color was input from the anterior, superior, inferior, nasal and temporal sides of the eye. These trainings started from the center of the normal visual field to the terminal of the visual field. When the training media reached the terminal of the visual field in every direction, ocular fixation with 2-5 seconds was performed to increase the scope of the visual field. Each stimulation was given 5-10 times for each direction. In the early periods of the training, when the visual acuity was complete loss, the training sections were relatively independent. When the visual acuity of subjects was partially recovered, the training sections were mixed. In addition, many training techniques were used in this study. First, visual imagery training was used when the patients had complete or severe visual loss. Visual imagery training can be defined as a dynamic state during which the representation of a specific object is internally reactivated within visual memory without any overt visual input and that is governed by the principles of central visual control. The intervention of the VI training was as follows: the subjects used the intact eye to observe the object for 5 seconds, then the participants closed their eyes and imagined viewing the object using the injured eye for 10 seconds for 10 repetitions. Additionally, proprioceptive training, including going over the barriers, going up and downstairs, walking the slope, and training the balance, was executed. Finally, constraint-induced perceptive therapy was performed when the visual lesion partially recovered. The subjects wore an eye patch on the intact eye for 30 minutes in one section, 2 to 4 hours a day, 7 days per week. In constraint-induced perceptive training, activities of daily living (ADL), natural environmental training and fun games with colorful objects were executed, and the subjects were instructed to complete the ADL, play gobang, watch the green leaves and colorful flowers from proximal to distal distance. All the subjects in the Reh group received perceptive learning therapy 5 days per week for 10 weeks except constraint-induced perceptive therapy.
Official Title
-----------------
Targeted Shortwave Diathermy Combined With Perceptual Training for Patients With Severe Traumatic Optic Neuropathy After Endoscopic Optic Nerve Decompression: a Preliminary Clinical Trial.
Conditions
-----------------
Traumatic Optic Neuropathy
Intervention / Treatment
-----------------
* Procedure: Rehabilitation: shortwave diathermy and perceptual training
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: The indications for endoscopic optic nerve decompression surgery included no improvement after intravenous treatment for 24 hours, no evidence of injury in the intracranial portion of the optic nerve, and the presence of bony fragments or hematoma compressing the optic nerve. TON with best-corrected visual acuity equal to or more than 1.85 logMAR after surgery was considered as severe TON, and those patients managed with endoscopic optic nerve decompression surgery were recruited in this study. Eligible criteria for the participants were as follows: (1) not receiving other physical therapy regimens aside from this intervention; (2) age 3 to 60 years old; (3) ability to execute simple verbal instructions; (4) not being delirious; (5) having stable vital signs and medical conditions. Exclusion criteria: The exclusion criteria included severe diffuse brain damage, and/or severe cardiac and pulmonary disease, which were contraindicated in rehabilitation procedure.
Ages Eligible for Study
-----------------
Minimum Age: 3 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Shortwave diathermy and perceptual training<br>The subjects in this group will receive shortwave diathermy 5 days per week for 4 weeks and perceptual training 5 days per week for 10 weeks after endoscopic optic nerve decompression surgery. | Procedure: Rehabilitation: shortwave diathermy and perceptual training<br>* All subjects in the rehabilitation group received shortwave diathermy therapy 5 days per week for 4 weeks and perceptual training 5 days per week for 10 weeks.<br>|
| No Intervention: Nonrehabilitation<br>The subjects in the nonrehabilitation group will not only receive any rehabilitation therapy after endoscopic optic nerve decompression surgery. | |
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI | A 32-channel head coil on a 3.0T MRI system (Philips, Ltd, Best, the Netherlands) was used for the acquisition of imaging data. T1- and T2-weighted, fat-suppressed images were obtained axially through the orbit and some parts of the brain, including the intracranial portion of the optic nerve, postoperatively and 10 weeks after rehabilitation. | 15 minutes |
| Diffusion tensor imaging | Optic nerve diffusion tensor imaging images were obtained using single-shot echoplanar imaging sequences. The images were acquired from the optic papilla to the orbital apex of the optic nerve with 40 contiguous slices. The region of interest was manually manually placed over the optic nerve at the anterior, middle, and posterior segments on the non-diffusion-weighted image. The fraction anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of optic nerves were measured. | 15 minutes |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual evoked potential | Pattern visual evoked potential testing was recorded using an MEB-9404C (Nihon Kohden Corp, Tokyo, Japan). The latency and amplitude of the P100 wave in the VEP testing were collected for analysis. | 30 minutes |
| Best-corrected visual acuity | Best-corrected visual acuity was measured by a standardized Snellen visual chart. Visual results were converted into logMAR units for the convenience of statistical analysis. Hand motion, light perception, and no light perception were converted to 2.3, 2.5, and 3 logMAR units, respectively. | 5 minutes |
| Color vision | Color vision was evaluated using the Ishihara color vision test 24 plate. The exclusion criterion of the color vision test was congenital color vision deficiency. The number of correct answers in a set of 24 plates was recorded as the color vision score. | 5 minutes |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Shortwave diathermy, perceptual training, traumatic optic neuropathy
|
NCT03196947
|
Safety and Pharmacokinetics of Rising Doses of APO010 in Relapsed/Refractory Multiple Myeloma Patients Selected by DRP
|
Multicentre, open label, uncontrolled, phase I pharmacokinetic study, to determine the Maximum Tolerated Dose (MTD) of APO010 administered intravenously on D1, D8 and D15 followed by a one-week drug rest, in patients with multiple myeloma for who have relapsed or are refractory to 2 (in high-risk patients 1) or more different prior therapies and who have Drug Response Predictor (DRP) for APO010 indicating a higher likelihood for response to APO010. The study will contain an extension phase where the recommended Dose will be tested on additional patients.
|
APO010 is a novel investigational antitumour agent. It is a recombinant form of human Fas ligand (FasL), a protein with the function of inducing programmed cell death (apoptosis). Preclinical studies indicate that multiple myeloma is sensitive for APO010. Estimation of DRP for APO010 in myeloma patients suggests that it may be possible to identify patients with high and low likelihood for response, and thereby allocate the predicted high likelihood patients to the treatment. Preclinical results indicate that, in comparison with other single agents, APO010 exercises superior anti-tumour effect by inducing apoptosis.~The study will include patients with multiple myeloma who have relapsed or are refractory to 2 (in high-risk patients 1) or more different prior therapies, including IMiDs and PI and who have Drug Response Predictor (DRP) for APO010 indicating a higher likelihood for response to APO010.~This study is a multicentre, open label, uncontrolled, phase I, dose escalation, pharmacokinetic study, to determine the Maximum Tolerated Dose (MTD) of APO010 administered intravenously on D1, D8 and D15 followed by a one-week drug rest i.e. cycle duration is 4 weeks. The study will contain an extension phase where the Recommended Dose will be tested on additional patients.~The primary endpoint is determination of the Maximum Tolerated Dose (MTD)based upon first cycle drug-related dose-limiting toxicity and the recommended dose of APO010. Safety will be evaluated during the study and for 30 days after the last administration of study drug. Adverse events and laboratory studies will be graded according to NCI-CTCAE v. 4.03.~The proportion of patients with positive HADA assessment will be investigated and a description of any objective tumour response based on International Myeloma Working Group criteria and from changes in M-protein and iFLC.
|
Phase I, Open Label, Dose Escalation Study to Investigate the Tolerability and Efficacy of APO010 in Patients With Relapsed/Refractory Multiple Myeloma Selected by Drug Response Predictor (DRP)
|
Relapsed/Refractory Multiple Myeloma
|
* Drug: APO010
|
Inclusion Criteria:~Relapsed or relapsed/refractory to 2 (in high-risk patients 1) or more different prior therapies, including IMiDs and PI~Measurable disease~Serum M-protein > 10 g/l, or~Urine M-protein > 200 mg/24 hours, or~Serum involved-FLC (iFLC) > 100 mg/l and abnormal FLC ratio~Have participated in the APO010 screening protocol in which Drug Response Predictor (DRP) outcome is measured as being in the upper likelihood of response (50% in dose-finding part and 25% in the expansion cohort)~Age > 18 years~Adequate organ and bone marrow function as defined below:~Absolute neutrophil count > 1.5 x 109/l (> 0.75 x 109/l in case > 50% plasma cell count in bone marrow)~Platelet count > 50 x 109/l (> 30 x 109/l in case > 50% plasma cell count in bone marrow)~Haemoglobin > 4.6 mmol/l (> 7.5 g/l)~Bilirubin ≤ upper limit of normal~aspartate aminotransferase (SGOT)/alanine transaminase (SGPT) ≤ upper limit of normal~Creatinine < 1.5 x upper limit of normal or creatinine clearance > 50 ml/min calculated according to Cockcroft-Gault~Eastern Cooperative Oncology Group (ECOG) performance status < 2~Life expectancy of at least 3 months.~Capability of understanding the nature of the study and giving written informed consent~Signed informed consent form~Exclusion Criteria:~Have central nervous system (CNS) myeloma~Have plasma cell leukaemia defined as plasma cell count > 2000 / µL in peripheral blood~Have symptomatic amyloidosis~Have anti-myeloma treatment or radiotherapy within 3 weeks from first infusion~Have received a cumulative dose of corticosteroid > 200 mg (dexamethasone, or equivalent dose of prednisone) within 2 weeks of the first infusion~Have received any experimental drug or experimental therapy within 3 weeks before the first infusion~Have received autologous-stem cell transplantation (SCT) within 12 weeks before the first infusion~Have received an allogeneic stem cell transplantation (SCT)~Have had past or current malignancy except for:~Cervical carcinoma < Stage 1B~Non-invasive basal cell or squamous cell skin carcinoma~Malignant melanoma with CR of > 10 years~Any other curable cancer with a CR > 5 years~Have major surgery within 4 weeks prior to the first infusion~Have severe infection requiring iv treatment~Have known HIV positivity~Have known active hepatitis B or C~Have had clinical significant arteriosclerotic events:~Ischemic heart disease~Unstable angina~Myocardial infarction~Transient ischemic attack~Ischemic stroke~Documented peripheral arteriosclerosis~Have baseline QT interval as corrected by Fridericia's formula (QTcF) > 470 msec for female patients or > 450 msec for male patients or a complete left bundle branch block (defined as QRS interval > 120 msec in left bundle branch block form)~CNS disease including epilepsy or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures~Women of childbearing age and potential who are not willing to use effective contraception during the study and at least until 90 days after last dose of study drug. Male patients or male patients who have female partners of childbearing age and potential who are not willing to use effective contraception during the study and at least until 90 days after last dose of study drug. Highly effective methods of birth control are defined as those which result in a low failure rate, i.e., less than 1% per year, when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomized partner~Pregnant or breast-feeding women
|
18 Years
| null |
All
|
No
|
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Dose Escalation followed by an extension phase using the recommended dosage
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dosage | To define the Maximum Tolerated Dosage of intravenous bolus administration of APO010 | 1 Year |
| Recommended Dosage | To define the Recommended Dosage of intravenous bolus administration of APO010 | 1 Year |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage (%) of patients with drug-related adverse events (adverse reactions) | To define the safety profile of a weekly schedule of APO010, including Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.03, Physical examination, vital signs, concomitant medications and laboratory data. To define the safety profile of APO010 after chronic administration (beyond 3 consecutive administrations, i.e., two or more cycles) and to define local toxicity at the site of administration through observation of the area of infusion. | 1 Year |
| The pharmacokinetic profile (AUC INF) for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated are Area Under the curve (AUC INF). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The pharmacokinetic profile (AUC last) for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated are Area Under the curve (AUC last). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The pharmacokinetic profile (AUC 0-12hr) for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated are Area Under the curve (AUC 0-12hr). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The Maximum Plasma Concentration (Cmax), for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated is Maximum Plasma Concentration (Cmax). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The Observed maximum (Tmax), for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated is, time of observed maximum (Tmax). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The Terminal half-life (T½), for APO010 at doses above 60 µg/m2 | Pharmacokinetic (PK) parameters will be calculated or estimated by using a model independent approach. The PK variable that will be evaluated is the terminal half-life (T½)). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The HADA Antibody Response | Assays will be performed to detect the production of antibodies against APO010 (HADA) in the serum of treated patients. If antibodies are formed, their ability to neutralize the biological activity of APO010 in in vitro cytotoxicity assay will be measured. | 1 Year |
| The Tumor Response | Using International Myeloma Working Group (IMWG) response criteria, based on measurements in blood and urine and in case of disappearance of M-proteins with additional confirmatory bone-marrow investigation, the number of patients with either stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD) or progressive disease (PD) will be measured. | 1 Year |
|
DRP, multiple myeloma, APO010, Drug Response Predictor
|
Paraproteinemias, Multiple Myeloma, Neoplasms, Plasma Cell, Neoplasms by Histologic Type, Neoplasms, Hemostatic Disorders, Vascular Diseases, Cardiovascular Diseases, Blood Protein Disorders, Hematologic Diseases, Hemorrhagic Disorders, Lymphoproliferative Disorders, Immunoproliferative Disorders, Immune System Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm, APO010 Dose escalation<br> | Drug: APO010<br>* APO010 is given iv on D1, D8 and D15 followed by a one-week drug rest (cycle duration 4 weeks).<br>|
|
Safety and Pharmacokinetics of Rising Doses of APO010 in Relapsed/Refractory Multiple Myeloma Patients Selected by DRP
Study Overview
=================
Brief Summary
-----------------
Multicentre, open label, uncontrolled, phase I pharmacokinetic study, to determine the Maximum Tolerated Dose (MTD) of APO010 administered intravenously on D1, D8 and D15 followed by a one-week drug rest, in patients with multiple myeloma for who have relapsed or are refractory to 2 (in high-risk patients 1) or more different prior therapies and who have Drug Response Predictor (DRP) for APO010 indicating a higher likelihood for response to APO010. The study will contain an extension phase where the recommended Dose will be tested on additional patients.
Detailed Description
-----------------
APO010 is a novel investigational antitumour agent. It is a recombinant form of human Fas ligand (FasL), a protein with the function of inducing programmed cell death (apoptosis). Preclinical studies indicate that multiple myeloma is sensitive for APO010. Estimation of DRP for APO010 in myeloma patients suggests that it may be possible to identify patients with high and low likelihood for response, and thereby allocate the predicted high likelihood patients to the treatment. Preclinical results indicate that, in comparison with other single agents, APO010 exercises superior anti-tumour effect by inducing apoptosis. The study will include patients with multiple myeloma who have relapsed or are refractory to 2 (in high-risk patients 1) or more different prior therapies, including IMiDs and PI and who have Drug Response Predictor (DRP) for APO010 indicating a higher likelihood for response to APO010. This study is a multicentre, open label, uncontrolled, phase I, dose escalation, pharmacokinetic study, to determine the Maximum Tolerated Dose (MTD) of APO010 administered intravenously on D1, D8 and D15 followed by a one-week drug rest i.e. cycle duration is 4 weeks. The study will contain an extension phase where the Recommended Dose will be tested on additional patients. The primary endpoint is determination of the Maximum Tolerated Dose (MTD)based upon first cycle drug-related dose-limiting toxicity and the recommended dose of APO010. Safety will be evaluated during the study and for 30 days after the last administration of study drug. Adverse events and laboratory studies will be graded according to NCI-CTCAE v. 4.03. The proportion of patients with positive HADA assessment will be investigated and a description of any objective tumour response based on International Myeloma Working Group criteria and from changes in M-protein and iFLC.
Official Title
-----------------
Phase I, Open Label, Dose Escalation Study to Investigate the Tolerability and Efficacy of APO010 in Patients With Relapsed/Refractory Multiple Myeloma Selected by Drug Response Predictor (DRP)
Conditions
-----------------
Relapsed/Refractory Multiple Myeloma
Intervention / Treatment
-----------------
* Drug: APO010
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Relapsed or relapsed/refractory to 2 (in high-risk patients 1) or more different prior therapies, including IMiDs and PI Measurable disease Serum M-protein > 10 g/l, or Urine M-protein > 200 mg/24 hours, or Serum involved-FLC (iFLC) > 100 mg/l and abnormal FLC ratio Have participated in the APO010 screening protocol in which Drug Response Predictor (DRP) outcome is measured as being in the upper likelihood of response (50% in dose-finding part and 25% in the expansion cohort) Age > 18 years Adequate organ and bone marrow function as defined below: Absolute neutrophil count > 1.5 x 109/l (> 0.75 x 109/l in case > 50% plasma cell count in bone marrow) Platelet count > 50 x 109/l (> 30 x 109/l in case > 50% plasma cell count in bone marrow) Haemoglobin > 4.6 mmol/l (> 7.5 g/l) Bilirubin ≤ upper limit of normal aspartate aminotransferase (SGOT)/alanine transaminase (SGPT) ≤ upper limit of normal Creatinine < 1.5 x upper limit of normal or creatinine clearance > 50 ml/min calculated according to Cockcroft-Gault Eastern Cooperative Oncology Group (ECOG) performance status < 2 Life expectancy of at least 3 months. Capability of understanding the nature of the study and giving written informed consent Signed informed consent form Exclusion Criteria: Have central nervous system (CNS) myeloma Have plasma cell leukaemia defined as plasma cell count > 2000 / µL in peripheral blood Have symptomatic amyloidosis Have anti-myeloma treatment or radiotherapy within 3 weeks from first infusion Have received a cumulative dose of corticosteroid > 200 mg (dexamethasone, or equivalent dose of prednisone) within 2 weeks of the first infusion Have received any experimental drug or experimental therapy within 3 weeks before the first infusion Have received autologous-stem cell transplantation (SCT) within 12 weeks before the first infusion Have received an allogeneic stem cell transplantation (SCT) Have had past or current malignancy except for: Cervical carcinoma < Stage 1B Non-invasive basal cell or squamous cell skin carcinoma Malignant melanoma with CR of > 10 years Any other curable cancer with a CR > 5 years Have major surgery within 4 weeks prior to the first infusion Have severe infection requiring iv treatment Have known HIV positivity Have known active hepatitis B or C Have had clinical significant arteriosclerotic events: Ischemic heart disease Unstable angina Myocardial infarction Transient ischemic attack Ischemic stroke Documented peripheral arteriosclerosis Have baseline QT interval as corrected by Fridericia's formula (QTcF) > 470 msec for female patients or > 450 msec for male patients or a complete left bundle branch block (defined as QRS interval > 120 msec in left bundle branch block form) CNS disease including epilepsy or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures Women of childbearing age and potential who are not willing to use effective contraception during the study and at least until 90 days after last dose of study drug. Male patients or male patients who have female partners of childbearing age and potential who are not willing to use effective contraception during the study and at least until 90 days after last dose of study drug. Highly effective methods of birth control are defined as those which result in a low failure rate, i.e., less than 1% per year, when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomized partner Pregnant or breast-feeding 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?
-----------------
Design Details
Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Dose Escalation followed by an extension phase using the recommended dosage
Masking: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm, APO010 Dose escalation<br> | Drug: APO010<br>* APO010 is given iv on D1, D8 and D15 followed by a one-week drug rest (cycle duration 4 weeks).<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dosage | To define the Maximum Tolerated Dosage of intravenous bolus administration of APO010 | 1 Year |
| Recommended Dosage | To define the Recommended Dosage of intravenous bolus administration of APO010 | 1 Year |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage (%) of patients with drug-related adverse events (adverse reactions) | To define the safety profile of a weekly schedule of APO010, including Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.03, Physical examination, vital signs, concomitant medications and laboratory data. To define the safety profile of APO010 after chronic administration (beyond 3 consecutive administrations, i.e., two or more cycles) and to define local toxicity at the site of administration through observation of the area of infusion. | 1 Year |
| The pharmacokinetic profile (AUC INF) for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated are Area Under the curve (AUC INF). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The pharmacokinetic profile (AUC last) for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated are Area Under the curve (AUC last). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The pharmacokinetic profile (AUC 0-12hr) for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated are Area Under the curve (AUC 0-12hr). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The Maximum Plasma Concentration (Cmax), for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated is Maximum Plasma Concentration (Cmax). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The Observed maximum (Tmax), for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated is, time of observed maximum (Tmax). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The Terminal half-life (T½), for APO010 at doses above 60 µg/m2 | Pharmacokinetic (PK) parameters will be calculated or estimated by using a model independent approach. The PK variable that will be evaluated is the terminal half-life (T½)). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year |
| The HADA Antibody Response | Assays will be performed to detect the production of antibodies against APO010 (HADA) in the serum of treated patients. If antibodies are formed, their ability to neutralize the biological activity of APO010 in in vitro cytotoxicity assay will be measured. | 1 Year |
| The Tumor Response | Using International Myeloma Working Group (IMWG) response criteria, based on measurements in blood and urine and in case of disappearance of M-proteins with additional confirmatory bone-marrow investigation, the number of patients with either stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD) or progressive disease (PD) will be measured. | 1 Year |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
DRP, multiple myeloma, APO010, Drug Response Predictor
|
NCT03416465
|
Place of General Medical During Oncology Care Management
|
The Purpose of MGPEC_ONCO is to see if patient consult their general practitioner during the management of their cancer, especially before hospitalization. The study concerns not planned hospitalizations in medicine service.~Before leaving hospital, the patient completes the survey, other data are taken in patient record
|
Place of General Medical During Oncology Care Management
|
Oncologic Disorders
|
* Behavioral: medical questionnaire
|
Inclusion Criteria:~Patient undergoing oncology treatment or ≤ 1 year of the latest oncology treatments~Patient hospitalized in a medical service in an unscheduled way~Age > or = 18 years old~Patient informed and not opposed to the study~Patient able and agreeing to follow all study procédures~Patient must be affiliated to a social security system~Exclusion Criteria:~Patient hospitalized in surgery and continuing care services~Patient deprived of liberty or under supervision
|
18 Years
| null |
All
|
No
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients in unscheduled hospitalization | Percentage of patients in unscheduled hospitalization who have seen their general practitioner | 1 day |
|
cancer, hospitalization, general practitioner
|
| Intervention/Treatment |
| --- |
|Behavioral: medical questionnaire|The patient will complete a questionnaire of 10 questions before leaving hospital. This questionnaire concerns the care pathway for hospitalized patients.|
|
Place of General Medical During Oncology Care Management
Study Overview
=================
Brief Summary
-----------------
The Purpose of MGPEC_ONCO is to see if patient consult their general practitioner during the management of their cancer, especially before hospitalization. The study concerns not planned hospitalizations in medicine service. Before leaving hospital, the patient completes the survey, other data are taken in patient record
Official Title
-----------------
Place of General Medical During Oncology Care Management
Conditions
-----------------
Oncologic Disorders
Intervention / Treatment
-----------------
* Behavioral: medical questionnaire
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient undergoing oncology treatment or ≤ 1 year of the latest oncology treatments Patient hospitalized in a medical service in an unscheduled way Age > or = 18 years old Patient informed and not opposed to the study Patient able and agreeing to follow all study procédures Patient must be affiliated to a social security system Exclusion Criteria: Patient hospitalized in surgery and continuing care services Patient deprived of liberty or under supervision
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 |
| --- |
|Behavioral: medical questionnaire|The patient will complete a questionnaire of 10 questions before leaving hospital. This questionnaire concerns the care pathway for hospitalized patients.|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients in unscheduled hospitalization | Percentage of patients in unscheduled hospitalization who have seen their general practitioner | 1 day |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cancer, hospitalization, general practitioner
|
||||
NCT03360409
|
Compare Different Cervical Anterior Discectomy Procedures by After Procedure Sagittal Alignment on Radiograph
|
Patients with single-level cervical degenerative disc disease commonly undertook anterior discectomy. To compare the effect of anterior cervical discectomy without fusion (ACD), anterior cervical discectomy with fusion by stand-alone cage (ACDF) or anterior cervical discectomy with arthroplasty (ACDA)， a multiple center randomised controlled trial will be performed in patients with single-level cervical disease. The primary outcome will be cervical alignment by upright cervical spine radiographs estimated by Harrison posterior tangent method.
|
This study will use a multiple center open-label randomised controlled trial to estimate the effect of ACD, ACDF, ACDA for single-level cervical degenerative disc. Patients with arm pain not responding to conservative treatment take part in this trial. They will be randomised assigned into 3 parallel arms. The participants in the each arm will undertake ACD ACDF or ACDA. The baseline is the day of surgery. The Harrison posterior tangent method was used as an estimate for measuring cervical alignment. The primary outcome will be the cervical sagittal alignment estimated by Harrison posterior tangent method.
|
Compare Different Cervical Anterior Discectomy Procedures for Cervical Degenerative Disc Disease by After Procedure Sagittal Alignment on Radiograph :a Multiple Center Randomized Controlled Trial
|
Cervical Disc Degeneration
|
* Procedure: ACD
* Procedure: ACDF
* Procedure: ACDA
|
Inclusion Criteria:~patients with arm pain not responding to conservative treatment~lasted longer than 10 weeks~single level disc degeneration~mobile spine on dynamic lateral cervical X-rays~Exclusion Criteria:~severe cardiopulmonary comorbidity~suspected underlying malignant disease~radicular syndrome~spinal-cord compression syndrome~contraindication for radiography
|
50 Years
|
80 Years
|
All
|
No
|
Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of cervical alignment | The Harrison posterior tangent method was used as an estimate for curvature | 1 day postoperatively, 6 weeks, 3 months, 1 year and 2 years |
|
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life | Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) | 1 day postoperatively, 6 weeks, 3 months, 1 year and 2 years |
|
Cervical Disc Degeneration, cervical anterior discectomy, Spinal alignment
|
Intervertebral Disc Degeneration, Spinal Diseases, Bone Diseases, Musculoskeletal Diseases
|
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: grade 1<br>ACD | Procedure: ACD<br>* Undertake anterior cervical discectomy without fusion<br>|
| Active Comparator: grade 2<br>ACDF | Procedure: ACDF<br>* anterior cervical discectomy with fusion<br>|
| Active Comparator: grade 3<br>ACDA | Procedure: ACDA<br>* anterior cervical discectomy with arthroplasty<br>|
|
Compare Different Cervical Anterior Discectomy Procedures by After Procedure Sagittal Alignment on Radiograph
Study Overview
=================
Brief Summary
-----------------
Patients with single-level cervical degenerative disc disease commonly undertook anterior discectomy. To compare the effect of anterior cervical discectomy without fusion (ACD), anterior cervical discectomy with fusion by stand-alone cage (ACDF) or anterior cervical discectomy with arthroplasty (ACDA)， a multiple center randomised controlled trial will be performed in patients with single-level cervical disease. The primary outcome will be cervical alignment by upright cervical spine radiographs estimated by Harrison posterior tangent method.
Detailed Description
-----------------
This study will use a multiple center open-label randomised controlled trial to estimate the effect of ACD, ACDF, ACDA for single-level cervical degenerative disc. Patients with arm pain not responding to conservative treatment take part in this trial. They will be randomised assigned into 3 parallel arms. The participants in the each arm will undertake ACD ACDF or ACDA. The baseline is the day of surgery. The Harrison posterior tangent method was used as an estimate for measuring cervical alignment. The primary outcome will be the cervical sagittal alignment estimated by Harrison posterior tangent method.
Official Title
-----------------
Compare Different Cervical Anterior Discectomy Procedures for Cervical Degenerative Disc Disease by After Procedure Sagittal Alignment on Radiograph :a Multiple Center Randomized Controlled Trial
Conditions
-----------------
Cervical Disc Degeneration
Intervention / Treatment
-----------------
* Procedure: ACD
* Procedure: ACDF
* Procedure: ACDA
Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patients with arm pain not responding to conservative treatment lasted longer than 10 weeks single level disc degeneration mobile spine on dynamic lateral cervical X-rays Exclusion Criteria: severe cardiopulmonary comorbidity suspected underlying malignant disease radicular syndrome spinal-cord compression syndrome contraindication for radiography
Ages Eligible for Study
-----------------
Minimum Age: 50 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: None (Open Label)
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: grade 1<br>ACD | Procedure: ACD<br>* Undertake anterior cervical discectomy without fusion<br>|
| Active Comparator: grade 2<br>ACDF | Procedure: ACDF<br>* anterior cervical discectomy with fusion<br>|
| Active Comparator: grade 3<br>ACDA | Procedure: ACDA<br>* anterior cervical discectomy with arthroplasty<br>|
What is the study measuring?
-----------------
Primary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of cervical alignment | The Harrison posterior tangent method was used as an estimate for curvature | 1 day postoperatively, 6 weeks, 3 months, 1 year and 2 years |
Secondary Outcome Measures
| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life | Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) | 1 day postoperatively, 6 weeks, 3 months, 1 year and 2 years |
Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cervical Disc Degeneration, cervical anterior discectomy, Spinal alignment
|
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