Desvenlafaxine in Opioid-Dependent Patients

• ClinicalTrials.gov Identifier: NCT02200406
• Recruitment Status: Completed
• First Posted: July 25, 2014
• Last Update Posted: October 23, 2020
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborator: Pfizer
• Information provided by (Responsible Party): Centre hospitalier de l'Université de Montréal (CHUM)

Tracking Information

• First Submitted Date: July 22, 2014
• First Posted Date: July 25, 2014
• Last Update Posted Date: October 23, 2020
• Study Start Date: July 2014
• Actual Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 10, 2015)

Tolerability: Systematic Assessment for Treatment Emergent Events (SAFTEE) [ Time Frame: 8 weeks ]

Safety and adverse effects with the Systematic Assessment for Treatment Emergent Events (SAFTEE)

Original Primary Outcome Measures (submitted: July 23, 2014)

• Feasibility: Proportion of persons screened who are eligible and enrolled [ Time Frame: Baseline ]
• Tolerability: Safety and adverse effects with the Systematic Assessment for Treatment Emergent Events (SAFTEE) [ Time Frame: 8 weeks ]
• Treatment adherence will be calculated as the total number of tablets dispensed minus the number returned, divided by the total number of tablets dispensed [ Time Frame: 8 weeks ]
• QT/QTc interval measures will be assessed by electrocardiograms (upper limit for safety should be 500ms). [ Time Frame: 4 weeks ]
• Feasibility: Proportion of scheduled study visits completed and biological samples collected [ Time Frame: 8 weeks ]
• Methadone serum level using gas chromatography mass spectroscopy (GCMS) [ Time Frame: 4 weeks ]
• Methadone dose [ Time Frame: 8 weeks ]

Current Secondary Outcome Measures (submitted: February 10, 2015)

• effect of Desvenlafaxine on depressive symptoms [ Time Frame: 8 weeks ]
  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.
• effect of Desvenlafaxine on depressive symptoms [ Time Frame: 8 weeks ]
  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.
• Response to treatment [ Time Frame: 8 weeks ]
  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
• Feasibility: Proportion of persons screened who are eligible and enrolled [ Time Frame: Baseline ]
  Proportion of persons screened who are eligible and enrolled
• Treatment adherence [ Time Frame: 8 weeks ]
  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
• Effect of Desvenlafaxine administration on QT/QTc interval prolongation [ Time Frame: 4 weeks ]
  It will be assessed by electrocardiograms (upper limit for safety should be 500ms).
• Feasibility: Proportion of scheduled study visits completed and biological samples collected [ Time Frame: 8 weeks ]
  Proportion of scheduled study visits completed and biological samples collected
• Potential for drug interactions between methadone and antidepressants - Effect of Desvenlafaxine on methadone serum level (pharmacokinetic variability) [ Time Frame: 4 weeks ]
  Change from baseline in methadone serum level. We will assessed the methadone serum level at baseline and after a month of treatment.
• Methadone dose adjustments [ Time Frame: 2 - 4 weeks ]
  Change from baseline in methadone dose. Each dose adjustment occurring during the trial will be noted at each follow-up visit

Original Secondary Outcome Measures (submitted: July 23, 2014)

• Depressive symptoms : 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. [ Time Frame: 8 weeks ]
• Depressive symptoms: 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. [ Time Frame: 8 weeks ]
• Response to treatment: 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 [ Time Frame: 8 weeks ]

Current Other Pre-specified Outcome Measures (submitted: February 10, 2015)

• Substance use [ Time Frame: 8 weeks ]
  number of days of substance use as assessed with The Time Line Follow-Back (TFLB), urine-drug testing and alcohol-breathalyzer testing.
• Effect of Desvenlafaxine on anxiety [ Time Frame: 8 weeks ]
  Change from Baseline in anxiety and mood. It will be assessed with the Hamilton Anxiety Rating Scale (HAM-A)
• Effect of Desvenlafaxine on blood pressure and heart rate [ Time Frame: 8 weeks ]
  Change from Baseline in Systolic Blood Pressure and heart rate
• Effect of Desvenlafaxine on opioid craving [ Time Frame: 8 weeks ]
  Assessed with the abbreviated Heroin Craving Questionnaire (HCQ) - Change from Baseline in Craving.
• Effect of Desvenlafaxine on quality of life [ Time Frame: 8 weeks ]
  Change from baseline in Quality of life. It will be assessed with the World Health Organization Quality of Life questionnaire (WHOQOL-BREF)
• Effect of Desvenlafaxine on disability [ Time Frame: 8 weeks ]
  Change from baseline in disability. It will be assessed with the Sheehan Disability Scale (SDS)
• Effect of Desvenlafaxine on suicidal behaviour [ Time Frame: 8 weeks ]
  Change from Baseline in suicidal behaviour. It will be assessed with the Columbia-Suicide Severity Rating Scale (CSSRS)
• Effect of Desvenlafaxine on testosterone level [ Time Frame: 4 weeks ]
  Change from Baseline in testosterone.

Original Other Pre-specified Outcome Measures (submitted: July 23, 2014)

• Substance use: number of days of substance use as assessed with The Time Line Follow-Back (TFLB), urine-drug testing and alcohol-breathalyzer testing. [ Time Frame: 8 weeks ]
• Anxiety: assessed with the Hamilton Anxiety Rating Scale (HAM-A) [ Time Frame: 8 weeks ]
• Blood pressure and heart rate [ Time Frame: 8 weeks ]
• Opioid craving: assessed with the abbreviated Heroin Craving Questionnaire (HCQ) [ Time Frame: 8 weeks ]
• Quality of life: assessed with the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) [ Time Frame: 8 weeks ]
• Disability: assessed with the Sheehan Disability Scale (SDS) [ Time Frame: 8 weeks ]
• Suicidality: assessed with the Columbia-Suicide Severity Rating Scale (CSSRS) [ Time Frame: 8 weeks ]
• Testosterone levels: measured using a chemiluminescence assay system [ Time Frame: 4 weeks ]

Descriptive Information

• Brief Title: Desvenlafaxine in Opioid-Dependent Patients
• Official Title: An Open-Label Pilot Study of Desvenlafaxine for Opioid-Dependent Patients With Comorbid Depression
• Brief Summary: 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.

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Depression
• Opioid Dependence
• Methadone Treatment

Intervention

Drug: Desvenlafaxine

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.

Other Name: PRISTIQ

Study Arms

Desvenlafaxine

• 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: Drug: Desvenlafaxine

• Publications *: El Hage C, Ghabrash MF, Dubreucq S, Brissette S, Lespérance F, Lespérance P, Ouellet-Plamondon C, Bruneau J, Jutras-Aswad D. A pilot, open-label, 8-week study evaluating desvenlafaxine for treatment of major depression in methadone-maintained individuals with opioid use disorder. Int Clin Psychopharmacol. 2018 Sep;33(5):268-273. doi: 10.1097/YIC.0000000000000223.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 15, 2017): 18
• Original Estimated Enrollment (submitted: July 23, 2014): 20
• Actual Study Completion Date: January 2017
• Actual Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• DSM-IV-TR criteria for opioid dependence;
• Subject is on methadone treatment in the substitution program for at least 4 weeks;
• Subject is aged between 18 and 65 years old;
• subject meets the DSM-V TR criteria for major depressive episode, according to the study psychiatrist and confirmed by the Mini International Neuropsychiatric Interview (MINI);
• Subject reports a score of 20 or higher on the MADRS;
• Subject is eligible for and consents to the study;
• subject is able to give valid, informed consent;
• subject is able to speak and read French or English (grade-nine level of language required)

Exclusion Criteria:

• Unstable medical illness, defined as any medical illness which has not been well-controlled with standard-of-care medications;
• Severe psychiatric condition (e.g., current acute psychosis, past or current hypomania/mania) based on the MINI;
• Pregnancy or breastfeeding;
• Inability to use a medically acceptable form of contraception throughout the study duration. A medically acceptable form of contraception is either: (1) contraceptive pill or intrauterine device or depot hormonal preparation (ring, injection, implant); and/or (2) a barrier method of contraception such as diaphragm, sponge with spermicide or condom;
• Subject currently takes another antidepressant;
• Treatment with Desvenlafaxine at any time in the past;
• Known hypersensitivity to venlafaxine;
• Subject is undergoing psychotherapies for current depression (support therapy or counseling are allowed);
• Subject failed to respond to two or more Health-Canada-approved antidepressants during current episode;
• Unstable Axis-II personality disorder or other Axis-II disorder which has been the primary focus of treatment in the past 3 months, as ascertained by a study psychiatrists;
• Medical diagnosis of kidney and/or liver failure

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT02200406
• Other Study ID Numbers: WI187002; Pfizer Reference Award Number ( Other Grant/Funding Number: WI187002 )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
• Study Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Pfizer

Investigators

• Principal Investigator: Didier Jutras-Aswad, M.D., M.Sc.; Centre hospitalier de l'Université de Montréal (CHUM)
• Study Chair: Suzanne Brissette, M.D., M.Sc.; Centre hospitalier de l'Université de Montréal (CHUM)
• Study Chair: Julie Bruneau, M.D., M.Sc.; Centre hospitalier de l'Université de Montréal (CHUM)
• Study Chair: Paul Lespérance, M.D., M.Sc.; Centre hospitalier de l'Université de Montréal (CHUM)
• Study Chair: Clairélaine Ouellet-Plamondon, M.D.; Centre hospitalier de l'Université de Montréal (CHUM)

• PRS Account: Centre hospitalier de l'Université de Montréal (CHUM)
• Verification Date: August 2017