xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06018467</url>
    </required_header>
    <id_info>
      <org_study_id>EU CT: 2022-502076-23-00</org_study_id>
      <secondary_id>2022-502076-23-00</secondary_id>
      <secondary_id>NNF21OC0067839</secondary_id>
      <nct_id>NCT06018467</nct_id>
    </id_info>
    <brief_title>SENolytics to Improve Osteoporosis Therapy</brief_title>
    <acronym>SENIOR</acronym>
    <official_title>SENolytics to Improve Osteoporosis Therapy: a Randomised Controlled Clinical Trial The SENIOR Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Odense University Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Odense Patient Data Explorative Network</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Novo Nordisk A/S</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Odense University Hospital</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This randomised clinical trial aims to study osteoporosis as a disease of accelerated&#xD;
        skeletal aging caused by the accumulation of senescent cells within the skeleton and&#xD;
        investigate the effects and safety of senolytics and antioxidant therapy on bone.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background, hypothesis, and aim:&#xD;
  &#xD;
        Evidence suggests that it is feasible to alleviate chronic age-related disorders by targeting&#xD;
        the biology of aging. Recent studies implicate cellular senescence at the nexus of skeletal&#xD;
        aging, suggesting that selectively eliminating senescent cells may emerge as a conceptually&#xD;
        novel approach to manage the enormous problem of age-related bone loss. In addition, previous&#xD;
        studies have demonstrated that antioxidants inhibit cellular senescence. The aim of this&#xD;
        randomised clinical trial is to study osteoporosis as a disease of accelerated skeletal aging&#xD;
        caused by accumulation of senescent cells within the skeleton and investigate the effects and&#xD;
        safety of senolytics and antioxidant therapy on bone.&#xD;
  &#xD;
        The main trial endpoint is the percent change in circulating marker of bone resorption (CTX)&#xD;
        measured at baseline and at week 21. Secondary endpoints are the changes in bone resorption&#xD;
        marker tartrate resistant acid phosphatase (TRAcP) and bone formation markers (PINP,&#xD;
        osteocalcin, and bone alkaline phosphatase) measured at baseline and at 21 weeks.&#xD;
  &#xD;
        Trial design:&#xD;
  &#xD;
        The study design is a randomised controlled open-label clinical trial. Study participants&#xD;
        will be randomised 1:1:1 to one of three treatment groups, that will include either,&#xD;
  &#xD;
          1. a combination of 100 mg/d dasatinib (oral) for two consecutive days and 1.250 mg/d&#xD;
             quercetin (oral) for three consecutive days followed by 25 days without treatment, with&#xD;
             treatment being repeated every 4 weeks for a total of 20 weeks (i.e., 5 times), or&#xD;
  &#xD;
          2. treatment with 1 g nicotinamide riboside (NR) (oral) daily for 20 weeks, or&#xD;
  &#xD;
          3. no treatment for 20 weeks.&#xD;
  &#xD;
        Each participant will have a total of 7 to 10 visits at the clinical site. Blood samples will&#xD;
        be obtained at all but one visit (2x20 ml each time). ECG will be performed at 6 visits for&#xD;
        group 1 and at 2 visits for group 2 and 3. Scans will be performed at the first two and the&#xD;
        last visit. Muscle-function tests will be performed at 2nd and last visit. Bone biopsies for&#xD;
        RNA-sequencing (a technique indicating which of the genes encoded in our DNA that are active)&#xD;
        will be collected in those that provide a separate consent and in up to 20 participants in&#xD;
        each group (using block randomisation to ensure balanced distribution of sex and age,&#xD;
        equaling a maximum of 60 biopsies.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2025</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Bone resorption marker CTX</measure>
      <time_frame>Baseline, week 5, week 13, week 21</time_frame>
      <description>Change in circulating marker of bone resorption C-terminal telopeptide of type I collagen (CTX) at 21 weeks.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Bone resorption marker TRAcP</measure>
      <time_frame>Baseline, week 5, week 13, week 21</time_frame>
      <description>Change in circulating marker of bone resorption Tartrate Resistant Acid Phosphatase (TRAcP) at 21 weeks.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Bone formation markers (PINP, osteocalcin, and bone alkaline phosphatase)</measure>
      <time_frame>Baseline, week 5, week 13, week 21</time_frame>
      <description>Change in circulating markers of bone formation (PINP, osteocalcin, and bone alkaline phosphatase) at 21 weeks.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Osteopenia, Osteoporosis</condition>
    <arm_group>
      <arm_group_label>Dasatinib plus Quercetin (DQ)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Study participants will receive a combination of 100 mg/d dasatinib (oral) for two consecutive days and 1.250 mg/d quercetin (oral) for three consecutive days followed by 25 days without treatment, with treatment being repeated every 4 weeks for a total of 20 weeks (i.e., 5 times)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Nicotinamide Riboside (NR)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The participants will receive treatment with 1g Nicotinamide Riboside (oral) daily for 20 weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>The participants in the Control group, will not receive any treatment for 20 weeks.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dasatinib 100 Mg Oral Tablet</intervention_name>
      <description>Dasatinib tablets in blister packs of 10 tablets, from either: &quot;Sandoz&quot;, &quot;STADA Nordic&quot;, &quot;Zentiva&quot; or &quot;Bristol-Myers Squibb&quot;</description>
      <arm_group_label>Dasatinib plus Quercetin (DQ)</arm_group_label>
      <other_name>Sprycel</other_name>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Quercetin 1.250 mg (oral)</intervention_name>
      <description>five 200mg Quercetin Phytosome capsules, from Thorne</description>
      <arm_group_label>Dasatinib plus Quercetin (DQ)</arm_group_label>
      <other_name>Quercetin Phytosome</other_name>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Nicotinamide Riboside 1g (oral)</intervention_name>
      <description>four 250mg Nicotinamide Riboside Capsules, from Elysium Health</description>
      <arm_group_label>Nicotinamide Riboside (NR)</arm_group_label>
      <other_name>NR</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Men and women (menopause &gt; 5 years and FSH and LH in the postmenopausal range) aged&#xD;
               60-90 years with increased fracture risk according to WHO 10 years absolute Fracture&#xD;
               Risk Assessment Tool (FRAX)&#xD;
  &#xD;
                 1. osteopenia (ICD10 DM858A) based on a T-score ≤ -2 to -2.5 at the total&#xD;
                    hip/femoral neck, or lumbar spine (FRAX score ranging from 10-70)&#xD;
  &#xD;
                 2. osteopenia (ICD10 DM858A) based on a T-score &lt; -1 to -2.5 and a fragility&#xD;
                    fracture at any time (excluding hip and vertebral fractures within the last 2&#xD;
                    years) (FRAX ranging from 11-68)&#xD;
  &#xD;
                 3. osteoporosis (ICD10 DM819) based on a T-score between &gt;-3 and ≤ -2.5, which&#xD;
                    includes candidates suitable for conventional osteoporosis therapies, but who&#xD;
                    prefer to participate in the trial, despite being candidates for conventional&#xD;
                    osteoporosis therapy, or candidates which cannot be treated with conventional&#xD;
                    therapies due to contraindications.&#xD;
  &#xD;
            -  Ability to provide informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  DXA of hip or spine not possible e.g., due to a prosthesis&#xD;
  &#xD;
            -  Inability to provide fasting blood samples&#xD;
  &#xD;
            -  Primary hyperparathyroidism&#xD;
  &#xD;
            -  Vitamin D deficiency (&lt;50 nM) (re-test after substitution acceptable)&#xD;
  &#xD;
            -  Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, chronic&#xD;
               kidney disease defined as eGFR &lt;30 or liver dysfunction, rheumatism, celiac&#xD;
               disease/malabsorption, hypogonadism, severe COPD, hypopituitarism, Cushing's disease,&#xD;
               uncontrolled diabetes (HbA1c &gt; 58 mmol/mol).&#xD;
  &#xD;
            -  Antiresorptive or bone anabolic drugs for the last 2 years (5 years if treated with&#xD;
               zoledronic acid)&#xD;
  &#xD;
            -  Concomitant treatments known to influence bone metabolism e.g., glucocorticoids&#xD;
               (systemic treatments), anabolic steroids, etc.&#xD;
  &#xD;
            -  Subjects taking the following other drugs if they cannot be held for at least 2 days&#xD;
               before and during administration of D+Q: digoxin, lithium, all statins, repaglidine,&#xD;
               bosentan, gemfibrozil, olmesartan, enalapril, valsartan, methotrexate,&#xD;
               corticosteroids, eluxadoline, eltrombopag, nitroglycerin, pioglitazone, glyburide,&#xD;
               enzalutamide, ezetimibe, colchicine, imatinib, cyclosporine, tacrolimus, sirolimus,&#xD;
               carbamazepine, flecainide, phenytoin, phenobarbital, rifampicin, theophylline,&#xD;
               warfarin, heparin, clopidogrel, celecoxib, desipramine, thioridazine, venlafaxine,&#xD;
               tizanidine, atomoxetine, voriconazole, citalopram, diazepam, escitalopram,&#xD;
               propranolol, clozapine, cyclobenzaprine, mexiletine, olanzapine, ondansetron&#xD;
  &#xD;
            -  Subjects taking medications that are sensitive to substrates or substrates with a&#xD;
               narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or&#xD;
               inducers of CYP3A4 (e.g., cyclosporine, tacrolimus or sirolimus). If antifungals are&#xD;
               necessary from an infectious disease perspective, then they will be allowed only if&#xD;
               the levels are therapeutic.&#xD;
  &#xD;
            -  Subjects taking proton pump inhibitors and unwilling to discontinue therapy for two&#xD;
               days before and during the study drug dosing periods.&#xD;
  &#xD;
            -  Anti-arrhythmic medications known to cause QTc prolongation&#xD;
  &#xD;
            -  Tyrosine kinase inhibitor therapy&#xD;
  &#xD;
            -  Subjects with an abnormal Complete Blood Count (clinically insignificant changes would&#xD;
               be acceptable based on the judgement of the investigators)&#xD;
  &#xD;
            -  Subjects on antiplatelet agents (Clopidogrel; Dipyridamole + ASA; ASA, Ticagrelor;&#xD;
               Prasugrel; Ticlopidine or other) who are unable or unwilling to reduce or hold therapy&#xD;
               prior to and during the study drug dosing periods and collection of bone biopsies.&#xD;
               Subjects may continue their previous regimen between study drug dosing periods.&#xD;
  &#xD;
            -  Known allergy to dasatinib, quercetin, or nicotinamide riboside&#xD;
  &#xD;
            -  Subjects taking the following antimicrobial agents: Aminoglycosides, Azole antifungals&#xD;
               (fluconazole, miconazole, voriconazole, itraconazole), Macrolides (clarithromycin,&#xD;
               erythromycin), antivirals (nelfinavir, indinavir, saquinavir, ritonavir,&#xD;
               elbasvir/grazoprevir)&#xD;
  &#xD;
            -  Presence of any condition the Investigator believes would place the subject at risk or&#xD;
               would preclude the subject from successfully completing all aspects of the trial e.g.,&#xD;
               heart failure, malignancy etc.&#xD;
  &#xD;
            -  QTc &gt;470 msec&#xD;
  &#xD;
            -  Inability to take oral medication&#xD;
  &#xD;
            -  The study will exclude subjects with inability to speak and understand Danish and with&#xD;
               inability to cooperate&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>60 Years</minimum_age>
      <maximum_age>90 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Moustapha Kassem, DMSc, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Head of Research, Department of Endocrinology, Odense University Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Shakespeare Jeromdesella, MD</last_name>
      <phone>+4521351927</phone>
      <email>shakespeare.jeromdesella@rsyd.dk</email>
    </overall_contact>
    <location>
      <facility>
        <name>Odense University Hospital</name>
        <address>
          <city>Odense</city>
          <zip>5000</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Shakespeare Jeromdesella, MD</last_name>
        <phone>+4521351927</phone>
        <email>shakespeare.jeromdesella@rsyd.dk</email>
      </contact>
      <investigator>
        <last_name>Moustapha Kassem, DMSc, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Morten F Nielsen, MD, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Denmark</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 23, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Age related bone loss</keyword>
    <keyword>Cellular senescence</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Osteoporosis</mesh_term>
      <mesh_term>Bone Diseases, Metabolic</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Niacinamide</mesh_term>
      <mesh_term>Niacin</mesh_term>
      <mesh_term>Nicotinic Acids</mesh_term>
      <mesh_term>Dasatinib</mesh_term>
      <mesh_term>Quercetin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>After completion of the project and irrespective of the outcomes, de-identified trial results will be published in peer-reviewed journals and www.clinicaltrials.gov. A summary of the clinical trial results will be presented in a language understandable to the layperson and made available in the EU database.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06018467
  org study id: EU CT: 2022-502076-23-00
  secondary id: 2022-502076-23-00
  secondary id: NNF21OC0067839
  nct id: NCT06018467
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This randomised clinical trial aims to study osteoporosis as a disease of accelerated
        skeletal aging caused by the accumulation of senescent cells within the skeleton and
        investigate the effects and safety of senolytics and antioxidant therapy on bone.
  Background, hypothesis, and aim:
  
        Evidence suggests that it is feasible to alleviate chronic age-related disorders by targeting
        the biology of aging. Recent studies implicate cellular senescence at the nexus of skeletal
        aging, suggesting that selectively eliminating senescent cells may emerge as a conceptually
        novel approach to manage the enormous problem of age-related bone loss. In addition, previous
        studies have demonstrated that antioxidants inhibit cellular senescence. The aim of this
        randomised clinical trial is to study osteoporosis as a disease of accelerated skeletal aging
        caused by accumulation of senescent cells within the skeleton and investigate the effects and
        safety of senolytics and antioxidant therapy on bone.
  
        The main trial endpoint is the percent change in circulating marker of bone resorption (CTX)
        measured at baseline and at week 21. Secondary endpoints are the changes in bone resorption
        marker tartrate resistant acid phosphatase (TRAcP) and bone formation markers (PINP,
        osteocalcin, and bone alkaline phosphatase) measured at baseline and at 21 weeks.
  
        Trial design:
  
        The study design is a randomised controlled open-label clinical trial. Study participants
        will be randomised 1:1:1 to one of three treatment groups, that will include either,
  
          1. a combination of 100 mg/d dasatinib (oral) for two consecutive days and 1.250 mg/d
             quercetin (oral) for three consecutive days followed by 25 days without treatment, with
             treatment being repeated every 4 weeks for a total of 20 weeks (i.e., 5 times), or
  
          2. treatment with 1 g nicotinamide riboside (NR) (oral) daily for 20 weeks, or
  
          3. no treatment for 20 weeks.
  
        Each participant will have a total of 7 to 10 visits at the clinical site. Blood samples will
        be obtained at all but one visit (2x20 ml each time). ECG will be performed at 6 visits for
        group 1 and at 2 visits for group 2 and 3. Scans will be performed at the first two and the
        last visit. Muscle-function tests will be performed at 2nd and last visit. Bone biopsies for
        RNA-sequencing (a technique indicating which of the genes encoded in our DNA that are active)
        will be collected in those that provide a separate consent and in up to 20 participants in
        each group (using block randomisation to ensure balanced distribution of sex and age,
        equaling a maximum of 60 biopsies.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  measure: Bone resorption marker CTX
  time frame: Baseline, week 5, week 13, week 21
  description: Change in circulating marker of bone resorption C-terminal telopeptide of type I collagen (CTX) at 21 weeks.
  measure: Bone resorption marker TRAcP
  time frame: Baseline, week 5, week 13, week 21
  description: Change in circulating marker of bone resorption Tartrate Resistant Acid Phosphatase (TRAcP) at 21 weeks.
  measure: Bone formation markers (PINP, osteocalcin, and bone alkaline phosphatase)
  time frame: Baseline, week 5, week 13, week 21
  description: Change in circulating markers of bone formation (PINP, osteocalcin, and bone alkaline phosphatase) at 21 weeks.
  arm group label: Dasatinib plus Quercetin (DQ)
  arm group type: Experimental
  description: Study participants will receive a combination of 100 mg/d dasatinib (oral) for two consecutive days and 1.250 mg/d quercetin (oral) for three consecutive days followed by 25 days without treatment, with treatment being repeated every 4 weeks for a total of 20 weeks (i.e., 5 times)
  arm group label: Nicotinamide Riboside (NR)
  arm group type: Experimental
  description: The participants will receive treatment with 1g Nicotinamide Riboside (oral) daily for 20 weeks
  arm group label: Control
  arm group type: No Intervention
  description: The participants in the Control group, will not receive any treatment for 20 weeks.
  intervention type: Drug
  intervention name: Dasatinib 100 Mg Oral Tablet
  description: Dasatinib tablets in blister packs of 10 tablets, from either: "Sandoz", "STADA Nordic", "Zentiva" or "Bristol-Myers Squibb"
  arm group label: Dasatinib plus Quercetin (DQ)
  other name: Sprycel
  intervention type: Dietary Supplement
  intervention name: Quercetin 1.250 mg (oral)
  description: five 200mg Quercetin Phytosome capsules, from Thorne
  arm group label: Dasatinib plus Quercetin (DQ)
  other name: Quercetin Phytosome
  intervention type: Dietary Supplement
  intervention name: Nicotinamide Riboside 1g (oral)
  description: four 250mg Nicotinamide Riboside Capsules, from Elysium Health
  arm group label: Nicotinamide Riboside (NR)
  other name: NR
  criteria: 
  gender: All
  minimum age: 60 Years
  maximum age: 90 Years
  healthy volunteers: No
  last name: Moustapha Kassem, DMSc, PhD
  role: Principal Investigator
  affiliation: Head of Research, Department of Endocrinology, Odense University Hospital
  last name: Shakespeare Jeromdesella, MD
  phone: +4521351927
  email: shakespeare.jeromdesella@rsyd.dk
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  investigator: 
  country: Denmark
  responsible party type: Sponsor
  mesh term: Osteoporosis
  mesh term: Bone Diseases, Metabolic
  mesh term: Niacinamide
  mesh term: Niacin
  mesh term: Nicotinic Acids
  mesh term: Dasatinib
  mesh term: Quercetin
  sharing ipd: No
  ipd description: After completion of the project and irrespective of the outcomes, de-identified trial results will be published in peer-reviewed journals and www.clinicaltrials.gov. A summary of the clinical trial results will be presented in a language understandable to the layperson and made available in the EU database.