<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/NCT02263248</url>
  </required_header>
  <id_info>
    <org_study_id>035/2014</org_study_id>
    <nct_id>NCT02263248</nct_id>
  </id_info>
  <brief_title>Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine</brief_title>
  <acronym>(IRLGREY-B)</acronym>
  <official_title>Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Addiction and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Reckitt Benckiser LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre for Addiction and Mental Health</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Investigators are conducting a research study to learn about the safety and benefit of&#xD;
      using a medication called buprenorphine for patient with difficult to treat depression . This&#xD;
      research study is testing whether combining two medications will be effective in treating&#xD;
      depression when initial treatment with just one antidepressant does not relieve the&#xD;
      depressive symptoms ; this is what is called &quot; difficult to treat depression &quot; or &quot; treatment&#xD;
      resistant depression &quot;. The two medication the investigators are using are &quot; an&#xD;
      anti-depressant medication called venlafaxine XR ( the generic form of Effexor ) and&#xD;
      buprenorphine . Buprenorphine is a medication that is FDA approved for the treatment of&#xD;
      opioid dependence. The investigators are testing whether adding buprenorphine to venlafaxine&#xD;
      enhances treatment response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this study is to examine the feasibility, safety, and tolerability of&#xD;
      buprenorphine (BPN) as a novel treatment for late-life treatment resistant depression&#xD;
      (LL-TRD). The investigators aim to use a clinical trial methodology common to all three&#xD;
      sites, and to examine the mechanism of action (MOA) of BPN using translational neuroscience&#xD;
      methods. Over ½ of seniors with depression fail to respond to traditional&#xD;
      antidepressants.19,20 Modulation of the opiate system with BPN offers a novel mechanistic&#xD;
      approach to improve the lives of patients with LL-TRD, with a safety profile potentially&#xD;
      superior to current augmentation strategies such as antipsychotics, lithium, ECT, and&#xD;
      surgical interventions (e.g., deep brain or vagal nerve stimulation).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">May 1, 2018</completion_date>
  <primary_completion_date type="Actual">January 19, 2017</primary_completion_date>
  <phase>Phase 1/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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Montgomery-Asberg Depression Rating Scale</measure>
    <time_frame>32 weeks</time_frame>
    <description>MADRS at baseline will establish study eligibility and will assess treatment-sensitive change in MDD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Suicidal Ideation Scale ( SIS)</measure>
    <time_frame>32 weeks</time_frame>
    <description>Assess suicidal ideation and previous suicide attempts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Brief Symptom Inventory for Anxiety</measure>
    <time_frame>32 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numeric Scale of Pain ( NRS-P)</measure>
    <time_frame>16 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)</measure>
    <time_frame>16 weeks</time_frame>
    <description>Assess overall burden or degree of interference in day-to-day activities and function due to the side effects attributable specifically to the antidepressant (in this case, buprenorphine) treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antidepressant Side Effect Checklist (ASEC)</measure>
    <time_frame>16 weeks</time_frame>
    <description>Assessment of side- effects</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>venlafaxine XR plus buprenorphine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug Intervention: venlafaxine XR plus buprenorphine Dosage varies. Subject remains on antidepressant throughout the 32 week study. Will be randomized to buprenorphine or placebo for up to 16 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>venlafaxine XR plus placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Drug Intervention: venlafaxine XR plus placebo Dosage varies . Subject remains on antidepressant throughout the 32 weeks study. Will be randomized to buprenorphine or placebo for up to 16 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>venlafaxine</intervention_name>
    <description>slow titration to a maximum of 300 mg per day. will remain on venlafaxine XR for upto 32 weeks.</description>
    <arm_group_label>venlafaxine XR plus buprenorphine</arm_group_label>
    <arm_group_label>venlafaxine XR plus placebo</arm_group_label>
    <other_name>Effexor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>buprenorphine</intervention_name>
    <description>randomized to either buprenorphine or placebo, dose range from 0.2 mg qd/ to 1.2 mg qd</description>
    <arm_group_label>venlafaxine XR plus buprenorphine</arm_group_label>
    <other_name>Temgesic</other_name>
    <other_name>Subutex</other_name>
    <other_name>Suboxone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>patients will remain on venlafaxine XR and be randomzied to receive either placebo or buprenorphine for 8 weeks. at the end of 8 weeks those who did not receive buprenorphine will be given an opportunity to try it.</description>
    <arm_group_label>venlafaxine XR plus placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &gt; 50 years&#xD;
&#xD;
          2. Major depressive disorder (MDD), single or recurrent, as diagnosed by the SCID-IV (or&#xD;
             SCID-5 if available)&#xD;
&#xD;
          3. MADRS &gt; 15&#xD;
&#xD;
          4. Has or agrees to establish a clinical relationship with primary care physician (PCP).&#xD;
&#xD;
          5. Availability of an informant (e.g., emergency contact) is encouraged but not required&#xD;
             for study participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to provide informed consent&#xD;
&#xD;
          2. Depressive symptoms not severe enough (i.e., MADRS &lt; 15) at the baseline assessments&#xD;
&#xD;
          3. Dementia, as defined by 3MS &lt; 80 and clinical evidence of dementia&#xD;
&#xD;
          4. Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective&#xD;
             disorder, schizophreniform disorder, delusional disorder, or current psychotic&#xD;
             symptoms, as diagnosed by the SCID&#xD;
&#xD;
          5. Abuse of or dependence on alcohol or other substances within the past 3 months as&#xD;
             determined by SCID, and score of &gt; 8 on AUDIT-C and confirmed by study physician&#xD;
             interview&#xD;
&#xD;
          6. High risk for suicide (e.g., active SI and/or current/recent intent or plan) AND&#xD;
             unable to be managed safely in the clinical trial (e.g., unwilling to be&#xD;
             hospitalized). Urgent psychiatric referral will be made in these cases&#xD;
&#xD;
          7. Contraindication to venlafaxine or buprenorphine as determined by PCP and study&#xD;
             physician including history of intolerance of either venlafaxine or buprenorphine in&#xD;
             the study target dosage range (venlafaxine at up to 300 mg/day; buprenorphine at up to&#xD;
             1.2 mg/day)&#xD;
&#xD;
          8. Inability to communicate in English (i.e., interview cannot be conducted without an&#xD;
             interpreter; subject largely unable to understand questions and cannot respond in&#xD;
             English)&#xD;
&#xD;
          9. Non-correctable clinically significant sensory impairment (i.e., cannot hear well&#xD;
             enough to cooperate with interview)&#xD;
&#xD;
         10. Unstable medical illness, including delirium, uncontrolled diabetes mellitus,&#xD;
             hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that&#xD;
             are not under medical management. This will be determined based on information from&#xD;
             the patient's personal physician and study physician's clinical judgment. Referral to&#xD;
             the patient's personal physician or to a general practitioner will be made in these&#xD;
             cases&#xD;
&#xD;
         11. Subjects taking psychotropic medications that cannot be safely tapered and&#xD;
             discontinued prior to study initiation. The following exceptions are allowed if they&#xD;
             have been taken at a stable dose for at least 4 weeks prior to study entry and there&#xD;
             is not a plan to change the dose during the next 32 -36 weeks: benzodiazepines up to 2&#xD;
             mg/d lorazepam equivalent; other sedative-hypnotics (e.g., zolpidem, zaleplon,&#xD;
             eszopiclone); gabapentin if prescribed for non-psychiatric indication (e.g.,&#xD;
             neuropathy)&#xD;
&#xD;
         12. History of opiate abuse or dependence&#xD;
&#xD;
         13. Severe pain, defined as &gt; 7 on 0-10 numeric rating scale for pain&#xD;
&#xD;
         14. Concomitant use of strong or moderate CYP3A4 inhibitor (indinavir, nelfinavir,&#xD;
             ritonavir, clarithromycin, itraconazole, ketonazole, nefazodone, saquinovir,&#xD;
             telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil,&#xD;
             diltiazem)&#xD;
&#xD;
         15. Refusal to stop all opioids (to avoid precipitating opioid withdrawal)&#xD;
&#xD;
         16. Refusal to discontinue all alcohol (to reduce the risk of respiratory depression)&#xD;
&#xD;
         17. Hepatic impairment (AST/ALT &gt; 1.5 times upper normal)&#xD;
&#xD;
         18. Estimated Glomerular Filtration Rate (GFR) &lt; 20 ml/min&#xD;
&#xD;
         19. Inability/refusal to identify a person as an emergency contact&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel M Blumberger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CAMH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre for Addiction and Mental Health</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M6J1H4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>October 8, 2014</study_first_submitted>
  <study_first_submitted_qc>October 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>July 24, 2018</last_update_submitted>
  <last_update_submitted_qc>July 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre for Addiction and Mental Health</investigator_affiliation>
    <investigator_full_name>Daniel Blumberger</investigator_full_name>
    <investigator_title>Dr. Daniel. M. Blumberger</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Buprenorphine</mesh_term>
    <mesh_term>Venlafaxine Hydrochloride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT02263248
org study id: 035/2014
nct id: NCT02263248
lead sponsor: 
collaborator: 
has dmc: Yes
The Investigators are conducting a research study to learn about the safety and benefit of
      using a medication called buprenorphine for patient with difficult to treat depression . This
      research study is testing whether combining two medications will be effective in treating
      depression when initial treatment with just one antidepressant does not relieve the
      depressive symptoms ; this is what is called " difficult to treat depression " or " treatment
      resistant depression ". The two medication the investigators are using are " an
      anti-depressant medication called venlafaxine XR ( the generic form of Effexor ) and
      buprenorphine . Buprenorphine is a medication that is FDA approved for the treatment of
      opioid dependence. The investigators are testing whether adding buprenorphine to venlafaxine
      enhances treatment response.
The aim of this study is to examine the feasibility, safety, and tolerability of
      buprenorphine (BPN) as a novel treatment for late-life treatment resistant depression
      (LL-TRD). The investigators aim to use a clinical trial methodology common to all three
      sites, and to examine the mechanism of action (MOA) of BPN using translational neuroscience
      methods. Over ½ of seniors with depression fail to respond to traditional
      antidepressants.19,20 Modulation of the opiate system with BPN offers a novel mechanistic
      approach to improve the lives of patients with LL-TRD, with a safety profile potentially
      superior to current augmentation strategies such as antipsychotics, lithium, ECT, and
      surgical interventions (e.g., deep brain or vagal nerve stimulation).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: The Montgomery-Asberg Depression Rating Scale
time frame: 32 weeks
description: MADRS at baseline will establish study eligibility and will assess treatment-sensitive change in MDD.
measure: Suicidal Ideation Scale ( SIS)
time frame: 32 weeks
description: Assess suicidal ideation and previous suicide attempts
measure: Brief Symptom Inventory for Anxiety
time frame: 32 weeks
measure: Numeric Scale of Pain ( NRS-P)
time frame: 16 weeks
measure: Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)
time frame: 16 weeks
description: Assess overall burden or degree of interference in day-to-day activities and function due to the side effects attributable specifically to the antidepressant (in this case, buprenorphine) treatment
measure: Antidepressant Side Effect Checklist (ASEC)
time frame: 16 weeks
description: Assessment of side- effects
arm group label: venlafaxine XR plus buprenorphine
arm group type: Experimental
description: Drug Intervention: venlafaxine XR plus buprenorphine Dosage varies. Subject remains on antidepressant throughout the 32 week study. Will be randomized to buprenorphine or placebo for up to 16 weeks.
arm group label: venlafaxine XR plus placebo
arm group type: Placebo Comparator
description: Drug Intervention: venlafaxine XR plus placebo Dosage varies . Subject remains on antidepressant throughout the 32 weeks study. Will be randomized to buprenorphine or placebo for up to 16 weeks
intervention type: Drug
intervention name: venlafaxine
description: slow titration to a maximum of 300 mg per day. will remain on venlafaxine XR for upto 32 weeks.
arm group label: venlafaxine XR plus buprenorphine
arm group label: venlafaxine XR plus placebo
other name: Effexor
intervention type: Drug
intervention name: buprenorphine
description: randomized to either buprenorphine or placebo, dose range from 0.2 mg qd/ to 1.2 mg qd
arm group label: venlafaxine XR plus buprenorphine
other name: Temgesic
other name: Subutex
other name: Suboxone
intervention type: Drug
intervention name: placebo
description: patients will remain on venlafaxine XR and be randomzied to receive either placebo or buprenorphine for 8 weeks. at the end of 8 weeks those who did not receive buprenorphine will be given an opportunity to try it.
arm group label: venlafaxine XR plus placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel M Blumberger, MD
role: Principal Investigator
affiliation: CAMH
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Centre for Addiction and Mental Health
investigator full name: Daniel Blumberger
investigator title: Dr. Daniel. M. Blumberger
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Buprenorphine
mesh term: Venlafaxine Hydrochloride
sharing ipd: Undecided