<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/NCT02200406</url>
  </required_header>
  <id_info>
    <org_study_id>WI187002</org_study_id>
    <secondary_id>Pfizer Reference Award Number</secondary_id>
    <nct_id>NCT02200406</nct_id>
  </id_info>
  <brief_title>Desvenlafaxine in Opioid-Dependent Patients</brief_title>
  <official_title>An Open-Label Pilot Study of Desvenlafaxine for Opioid-Dependent Patients With Comorbid Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre hospitalier de l'Université de Montréal (CHUM)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre hospitalier de l'Université de Montréal (CHUM)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Although substitution therapy has been shown to be highly effective to retain&#xD;
      opioid-dependent patients in treatment and reduce drug use, this population is afflicted by&#xD;
      numerous conditions including depression. Unfortunately, studies published thus far have&#xD;
      reported inconsistent or no difference in response between placebo therapy and&#xD;
      antidepressants such as selective serotonin reuptake inhibitors. Objective: To assess the&#xD;
      feasibility of Desvenlafaxine (DESV) administration among opioid-dependent subjects and&#xD;
      explore its effect on depressive symptoms. Methods: Open-label pilot trial of 8 weeks of DESV&#xD;
      50-100 mg/day in 20 methadone-maintained individuals with comorbid depressive symptoms at the&#xD;
      Centre hospitalier de l'Université de Montréal. Significance: This pilot study will lay down&#xD;
      the foundation on which a larger multisite clinical trial could be conducted to examine DESV&#xD;
      as new treatment for opioid-dependent population with comorbid depression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To assess the feasibility, tolerability and acceptability of 8 weeks of Desvenlafaxine (DESV)&#xD;
      administration among opioid-dependent subjects in a methadone-maintenance program, we will&#xD;
      collect detailed information on compliance to DESV treatment, side effects, methadone plasma&#xD;
      levels, methadone dose changes and QTc measures.&#xD;
&#xD;
      To explore the effects of DESV on depressive symptoms among opioid-dependent subjects on&#xD;
      methadone-maintenance treatment. The severity and symptoms of depression will be evaluated by&#xD;
      using the MADRS, the HRDS, and the CGI scale.&#xD;
&#xD;
      To explore the effects of DESV on substance use, anxiety, craving, quality of life and&#xD;
      suicidal risk.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Tolerability: Systematic Assessment for Treatment Emergent Events (SAFTEE)</measure>
    <time_frame>8 weeks</time_frame>
    <description>Safety and adverse effects with the Systematic Assessment for Treatment Emergent Events (SAFTEE)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>effect of Desvenlafaxine on depressive symptoms</measure>
    <time_frame>8 weeks</time_frame>
    <description>Responders will be determined by a 50% reduction in (Hamilton Depression Rating Scale) HAM-D scores, and remitters will be determined based on scores of ≤7.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>effect of Desvenlafaxine on depressive symptoms</measure>
    <time_frame>8 weeks</time_frame>
    <description>Responders will be determined by a 50% reduction in the Montgomery-Asberg Depression Scale (MADRS) scores, and remitters will be determined based on scores of 10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response to treatment</measure>
    <time_frame>8 weeks</time_frame>
    <description>A favorable response will be defined as a score of 1 or 2 (very much or much improved) on the Clinical Global Impression CGI-I subscale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility: Proportion of persons screened who are eligible and enrolled</measure>
    <time_frame>Baseline</time_frame>
    <description>Proportion of persons screened who are eligible and enrolled</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment adherence</measure>
    <time_frame>8 weeks</time_frame>
    <description>Compliance will be evaluated at each in-person follow-up visit. Treatment adherence will be calculated as the total number of tablets dispensed minus the number returned, divided by the total number of tablets dispensed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of Desvenlafaxine administration on QT/QTc interval prolongation</measure>
    <time_frame>4 weeks</time_frame>
    <description>It will be assessed by electrocardiograms (upper limit for safety should be 500ms).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility: Proportion of scheduled study visits completed and biological samples collected</measure>
    <time_frame>8 weeks</time_frame>
    <description>Proportion of scheduled study visits completed and biological samples collected</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Potential for drug interactions between methadone and antidepressants - Effect of Desvenlafaxine on methadone serum level (pharmacokinetic variability)</measure>
    <time_frame>4 weeks</time_frame>
    <description>Change from baseline in methadone serum level. We will assessed the methadone serum level at baseline and after a month of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Methadone dose adjustments</measure>
    <time_frame>2 - 4 weeks</time_frame>
    <description>Change from baseline in methadone dose. Each dose adjustment occurring during the trial will be noted at each follow-up visit</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Substance use</measure>
    <time_frame>8 weeks</time_frame>
    <description>number of days of substance use as assessed with The Time Line Follow-Back (TFLB), urine-drug testing and alcohol-breathalyzer testing.</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of Desvenlafaxine on anxiety</measure>
    <time_frame>8 weeks</time_frame>
    <description>Change from Baseline in anxiety and mood. It will be assessed with the Hamilton Anxiety Rating Scale (HAM-A)</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of Desvenlafaxine on blood pressure and heart rate</measure>
    <time_frame>8 weeks</time_frame>
    <description>Change from Baseline in Systolic Blood Pressure and heart rate</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of Desvenlafaxine on opioid craving</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed with the abbreviated Heroin Craving Questionnaire (HCQ) - Change from Baseline in Craving.</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of Desvenlafaxine on quality of life</measure>
    <time_frame>8 weeks</time_frame>
    <description>Change from baseline in Quality of life. It will be assessed with the World Health Organization Quality of Life questionnaire (WHOQOL-BREF)</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of Desvenlafaxine on disability</measure>
    <time_frame>8 weeks</time_frame>
    <description>Change from baseline in disability. It will be assessed with the Sheehan Disability Scale (SDS)</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of Desvenlafaxine on suicidal behaviour</measure>
    <time_frame>8 weeks</time_frame>
    <description>Change from Baseline in suicidal behaviour. It will be assessed with the Columbia-Suicide Severity Rating Scale (CSSRS)</description>
  </other_outcome>
  <other_outcome>
    <measure>Effect of Desvenlafaxine on testosterone level</measure>
    <time_frame>4 weeks</time_frame>
    <description>Change from Baseline in testosterone.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Depression</condition>
  <condition>Opioid Dependence</condition>
  <condition>Methadone Treatment</condition>
  <arm_group>
    <arm_group_label>Desvenlafaxine</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Open-label pilot study&#xD;
Desvenlafaxine will be administered during 56 consecutive days&#xD;
Desvenlafaxine will be administered in the morning at a 50 mg dose during weeks 1 and 2, and at 50-100 mg doses (based on the study psychiatrist's judgment) during the 6 following weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Desvenlafaxine</intervention_name>
    <description>All subjects will receive 50 mg of the medication during week 1 and 2, then 50-100 mg (based on the psychiatrist judgment) for the following 6 weeks. Subjects who experience significant adverse reactions with the 100mg dose during weeks 2 to 4 could return to the lower dose of 50 mg if judged clinically appropriate by the study psychiatrist.</description>
    <arm_group_label>Desvenlafaxine</arm_group_label>
    <other_name>PRISTIQ</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  DSM-IV-TR criteria for opioid dependence;&#xD;
&#xD;
          -  Subject is on methadone treatment in the substitution program for at least 4 weeks;&#xD;
&#xD;
          -  Subject is aged between 18 and 65 years old;&#xD;
&#xD;
          -  subject meets the DSM-V TR criteria for major depressive episode, according to the&#xD;
             study psychiatrist and confirmed by the Mini International Neuropsychiatric Interview&#xD;
             (MINI);&#xD;
&#xD;
          -  Subject reports a score of 20 or higher on the MADRS;&#xD;
&#xD;
          -  Subject is eligible for and consents to the study;&#xD;
&#xD;
          -  subject is able to give valid, informed consent;&#xD;
&#xD;
          -  subject is able to speak and read French or English (grade-nine level of language&#xD;
             required)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unstable medical illness, defined as any medical illness which has not been&#xD;
             well-controlled with standard-of-care medications;&#xD;
&#xD;
          -  Severe psychiatric condition (e.g., current acute psychosis, past or current&#xD;
             hypomania/mania) based on the MINI;&#xD;
&#xD;
          -  Pregnancy or breastfeeding;&#xD;
&#xD;
          -  Inability to use a medically acceptable form of contraception throughout the study&#xD;
             duration. A medically acceptable form of contraception is either: (1) contraceptive&#xD;
             pill or intrauterine device or depot hormonal preparation (ring, injection, implant);&#xD;
             and/or (2) a barrier method of contraception such as diaphragm, sponge with spermicide&#xD;
             or condom;&#xD;
&#xD;
          -  Subject currently takes another antidepressant;&#xD;
&#xD;
          -  Treatment with Desvenlafaxine at any time in the past;&#xD;
&#xD;
          -  Known hypersensitivity to venlafaxine;&#xD;
&#xD;
          -  Subject is undergoing psychotherapies for current depression (support therapy or&#xD;
             counseling are allowed);&#xD;
&#xD;
          -  Subject failed to respond to two or more Health-Canada-approved antidepressants during&#xD;
             current episode;&#xD;
&#xD;
          -  Unstable Axis-II personality disorder or other Axis-II disorder which has been the&#xD;
             primary focus of treatment in the past 3 months, as ascertained by a study&#xD;
             psychiatrists;&#xD;
&#xD;
          -  Medical diagnosis of kidney and/or liver failure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Didier Jutras-Aswad, M.D., M.Sc.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre hospitalier de l'Université de Montréal (CHUM)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Suzanne Brissette, M.D., M.Sc.</last_name>
    <role>Study Chair</role>
    <affiliation>Centre hospitalier de l'Université de Montréal (CHUM)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Julie Bruneau, M.D., M.Sc.</last_name>
    <role>Study Chair</role>
    <affiliation>Centre hospitalier de l'Université de Montréal (CHUM)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Paul Lespérance, M.D., M.Sc.</last_name>
    <role>Study Chair</role>
    <affiliation>Centre hospitalier de l'Université de Montréal (CHUM)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Clairélaine Ouellet-Plamondon, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Centre hospitalier de l'Université de Montréal (CHUM)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre de recherche du Centre Hospitalier de l'Université de Montréal</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2X0A9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>October 21, 2020</last_update_submitted>
  <last_update_submitted_qc>October 21, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Desvenlafaxine</keyword>
  <keyword>Opioid-dependent</keyword>
  <keyword>Addiction</keyword>
  <keyword>Depression</keyword>
  <keyword>Methadone</keyword>
  <keyword>Comorbidity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Desvenlafaxine Succinate</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02200406
org study id: WI187002
secondary id: Pfizer Reference Award Number
nct id: NCT02200406
lead sponsor: 
collaborator: 
has dmc: Yes
Background: Although substitution therapy has been shown to be highly effective to retain
      opioid-dependent patients in treatment and reduce drug use, this population is afflicted by
      numerous conditions including depression. Unfortunately, studies published thus far have
      reported inconsistent or no difference in response between placebo therapy and
      antidepressants such as selective serotonin reuptake inhibitors. Objective: To assess the
      feasibility of Desvenlafaxine (DESV) administration among opioid-dependent subjects and
      explore its effect on depressive symptoms. Methods: Open-label pilot trial of 8 weeks of DESV
      50-100 mg/day in 20 methadone-maintained individuals with comorbid depressive symptoms at the
      Centre hospitalier de l'Université de Montréal. Significance: This pilot study will lay down
      the foundation on which a larger multisite clinical trial could be conducted to examine DESV
      as new treatment for opioid-dependent population with comorbid depression.
To assess the feasibility, tolerability and acceptability of 8 weeks of Desvenlafaxine (DESV)
      administration among opioid-dependent subjects in a methadone-maintenance program, we will
      collect detailed information on compliance to DESV treatment, side effects, methadone plasma
      levels, methadone dose changes and QTc measures.

      To explore the effects of DESV on depressive symptoms among opioid-dependent subjects on
      methadone-maintenance treatment. The severity and symptoms of depression will be evaluated by
      using the MADRS, the HRDS, and the CGI scale.

      To explore the effects of DESV on substance use, anxiety, craving, quality of life and
      suicidal risk.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Tolerability: Systematic Assessment for Treatment Emergent Events (SAFTEE)
time frame: 8 weeks
description: Safety and adverse effects with the Systematic Assessment for Treatment Emergent Events (SAFTEE)
measure: effect of Desvenlafaxine on depressive symptoms
time frame: 8 weeks
description: Responders will be determined by a 50% reduction in (Hamilton Depression Rating Scale) HAM-D scores, and remitters will be determined based on scores of ≤7.
measure: effect of Desvenlafaxine on depressive symptoms
time frame: 8 weeks
description: Responders will be determined by a 50% reduction in the Montgomery-Asberg Depression Scale (MADRS) scores, and remitters will be determined based on scores of 10.
measure: Response to treatment
time frame: 8 weeks
description: A favorable response will be defined as a score of 1 or 2 (very much or much improved) on the Clinical Global Impression CGI-I subscale
measure: Feasibility: Proportion of persons screened who are eligible and enrolled
time frame: Baseline
description: Proportion of persons screened who are eligible and enrolled
measure: Treatment adherence
time frame: 8 weeks
description: Compliance will be evaluated at each in-person follow-up visit. Treatment adherence will be calculated as the total number of tablets dispensed minus the number returned, divided by the total number of tablets dispensed
measure: Effect of Desvenlafaxine administration on QT/QTc interval prolongation
time frame: 4 weeks
description: It will be assessed by electrocardiograms (upper limit for safety should be 500ms).
measure: Feasibility: Proportion of scheduled study visits completed and biological samples collected
time frame: 8 weeks
description: Proportion of scheduled study visits completed and biological samples collected
measure: Potential for drug interactions between methadone and antidepressants - Effect of Desvenlafaxine on methadone serum level (pharmacokinetic variability)
time frame: 4 weeks
description: Change from baseline in methadone serum level. We will assessed the methadone serum level at baseline and after a month of treatment.
measure: Methadone dose adjustments
time frame: 2 - 4 weeks
description: Change from baseline in methadone dose. Each dose adjustment occurring during the trial will be noted at each follow-up visit
measure: Substance use
time frame: 8 weeks
description: number of days of substance use as assessed with The Time Line Follow-Back (TFLB), urine-drug testing and alcohol-breathalyzer testing.
measure: Effect of Desvenlafaxine on anxiety
time frame: 8 weeks
description: Change from Baseline in anxiety and mood. It will be assessed with the Hamilton Anxiety Rating Scale (HAM-A)
measure: Effect of Desvenlafaxine on blood pressure and heart rate
time frame: 8 weeks
description: Change from Baseline in Systolic Blood Pressure and heart rate
measure: Effect of Desvenlafaxine on opioid craving
time frame: 8 weeks
description: Assessed with the abbreviated Heroin Craving Questionnaire (HCQ) - Change from Baseline in Craving.
measure: Effect of Desvenlafaxine on quality of life
time frame: 8 weeks
description: Change from baseline in Quality of life. It will be assessed with the World Health Organization Quality of Life questionnaire (WHOQOL-BREF)
measure: Effect of Desvenlafaxine on disability
time frame: 8 weeks
description: Change from baseline in disability. It will be assessed with the Sheehan Disability Scale (SDS)
measure: Effect of Desvenlafaxine on suicidal behaviour
time frame: 8 weeks
description: Change from Baseline in suicidal behaviour. It will be assessed with the Columbia-Suicide Severity Rating Scale (CSSRS)
measure: Effect of Desvenlafaxine on testosterone level
time frame: 4 weeks
description: Change from Baseline in testosterone.
arm group label: Desvenlafaxine
arm group type: Other
description: Open-label pilot study
Desvenlafaxine will be administered during 56 consecutive days
Desvenlafaxine will be administered in the morning at a 50 mg dose during weeks 1 and 2, and at 50-100 mg doses (based on the study psychiatrist's judgment) during the 6 following weeks.
intervention type: Drug
intervention name: Desvenlafaxine
description: All subjects will receive 50 mg of the medication during week 1 and 2, then 50-100 mg (based on the psychiatrist judgment) for the following 6 weeks. Subjects who experience significant adverse reactions with the 100mg dose during weeks 2 to 4 could return to the lower dose of 50 mg if judged clinically appropriate by the study psychiatrist.
arm group label: Desvenlafaxine
other name: PRISTIQ
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Didier Jutras-Aswad, M.D., M.Sc.
role: Principal Investigator
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
last name: Suzanne Brissette, M.D., M.Sc.
role: Study Chair
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
last name: Julie Bruneau, M.D., M.Sc.
role: Study Chair
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
last name: Paul Lespérance, M.D., M.Sc.
role: Study Chair
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
last name: Clairélaine Ouellet-Plamondon, M.D.
role: Study Chair
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Opioid-Related Disorders
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Desvenlafaxine Succinate