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Desvenlafaxine in Opioid-Dependent Patients

Primary Purpose

Depression, Opioid Dependence, Methadone Treatment

Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Desvenlafaxine
Sponsored by
Centre hospitalier de l'Université de Montréal (CHUM)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression focused on measuring Desvenlafaxine, Opioid-dependent, Addiction, Depression, Methadone, Comorbidity

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Centre de recherche du Centre Hospitalier de l'Université de Montréal

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Desvenlafaxine

Arm 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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

effect of Desvenlafaxine on 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.
effect of Desvenlafaxine on 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.
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
Feasibility: Proportion of persons screened who are eligible and enrolled
Proportion of persons screened who are eligible and enrolled
Treatment adherence
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
It will be assessed by electrocardiograms (upper limit for safety should be 500ms).
Feasibility: Proportion of scheduled study visits completed and biological samples collected
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)
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
Change from baseline in methadone dose. Each dose adjustment occurring during the trial will be noted at each follow-up visit

Full Information

First Posted
July 22, 2014
Last Updated
October 21, 2020
Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT02200406
Brief Title
Desvenlafaxine in Opioid-Dependent Patients
Official Title
An Open-Label Pilot Study of Desvenlafaxine for Opioid-Dependent Patients With Comorbid Depression
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
Collaborators
Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Opioid Dependence, Methadone Treatment
Keywords
Desvenlafaxine, Opioid-dependent, Addiction, Depression, Methadone, Comorbidity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Desvenlafaxine
Arm Type
Other
Arm 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(s)
Desvenlafaxine
Other Intervention Name(s)
PRISTIQ
Intervention 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.
Primary Outcome Measure Information:
Title
Tolerability: Systematic Assessment for Treatment Emergent Events (SAFTEE)
Description
Safety and adverse effects with the Systematic Assessment for Treatment Emergent Events (SAFTEE)
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
effect of Desvenlafaxine on depressive symptoms
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.
Time Frame
8 weeks
Title
effect of Desvenlafaxine on depressive symptoms
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.
Time Frame
8 weeks
Title
Response to treatment
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
Time Frame
8 weeks
Title
Feasibility: Proportion of persons screened who are eligible and enrolled
Description
Proportion of persons screened who are eligible and enrolled
Time Frame
Baseline
Title
Treatment adherence
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
Time Frame
8 weeks
Title
Effect of Desvenlafaxine administration on QT/QTc interval prolongation
Description
It will be assessed by electrocardiograms (upper limit for safety should be 500ms).
Time Frame
4 weeks
Title
Feasibility: Proportion of scheduled study visits completed and biological samples collected
Description
Proportion of scheduled study visits completed and biological samples collected
Time Frame
8 weeks
Title
Potential for drug interactions between methadone and antidepressants - Effect of Desvenlafaxine on methadone serum level (pharmacokinetic variability)
Description
Change from baseline in methadone serum level. We will assessed the methadone serum level at baseline and after a month of treatment.
Time Frame
4 weeks
Title
Methadone dose adjustments
Description
Change from baseline in methadone dose. Each dose adjustment occurring during the trial will be noted at each follow-up visit
Time Frame
2 - 4 weeks
Other Pre-specified Outcome Measures:
Title
Substance use
Description
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
Title
Effect of Desvenlafaxine on anxiety
Description
Change from Baseline in anxiety and mood. It will be assessed with the Hamilton Anxiety Rating Scale (HAM-A)
Time Frame
8 weeks
Title
Effect of Desvenlafaxine on blood pressure and heart rate
Description
Change from Baseline in Systolic Blood Pressure and heart rate
Time Frame
8 weeks
Title
Effect of Desvenlafaxine on opioid craving
Description
Assessed with the abbreviated Heroin Craving Questionnaire (HCQ) - Change from Baseline in Craving.
Time Frame
8 weeks
Title
Effect of Desvenlafaxine on quality of life
Description
Change from baseline in Quality of life. It will be assessed with the World Health Organization Quality of Life questionnaire (WHOQOL-BREF)
Time Frame
8 weeks
Title
Effect of Desvenlafaxine on disability
Description
Change from baseline in disability. It will be assessed with the Sheehan Disability Scale (SDS)
Time Frame
8 weeks
Title
Effect of Desvenlafaxine on suicidal behaviour
Description
Change from Baseline in suicidal behaviour. It will be assessed with the Columbia-Suicide Severity Rating Scale (CSSRS)
Time Frame
8 weeks
Title
Effect of Desvenlafaxine on testosterone level
Description
Change from Baseline in testosterone.
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Didier Jutras-Aswad, M.D., M.Sc.
Organizational Affiliation
Centre hospitalier de l'Université de Montréal (CHUM)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Suzanne Brissette, M.D., M.Sc.
Organizational Affiliation
Centre hospitalier de l'Université de Montréal (CHUM)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Julie Bruneau, M.D., M.Sc.
Organizational Affiliation
Centre hospitalier de l'Université de Montréal (CHUM)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Paul Lespérance, M.D., M.Sc.
Organizational Affiliation
Centre hospitalier de l'Université de Montréal (CHUM)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Clairélaine Ouellet-Plamondon, M.D.
Organizational Affiliation
Centre hospitalier de l'Université de Montréal (CHUM)
Official's Role
Study Chair
Facility Information:
Facility Name
Centre de recherche du Centre Hospitalier de l'Université de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2X0A9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
29738425
Citation
El Hage C, Ghabrash MF, Dubreucq S, Brissette S, Lesperance F, Lesperance 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.
Results Reference
derived

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Desvenlafaxine in Opioid-Dependent Patients

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