- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02263248
Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine ((IRLGREY-B))
July 24, 2018 updated by: Daniel Blumberger, Centre for Addiction and Mental Health
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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).
Study Type
Interventional
Enrollment (Actual)
56
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ontario
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Toronto, Ontario, Canada, M6J1H4
- Centre for Addiction and Mental Health
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
48 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age > 50 years
- Major depressive disorder (MDD), single or recurrent, as diagnosed by the SCID-IV (or SCID-5 if available)
- MADRS > 15
- Has or agrees to establish a clinical relationship with primary care physician (PCP).
- Availability of an informant (e.g., emergency contact) is encouraged but not required for study participation
Exclusion Criteria:
- Inability to provide informed consent
- Depressive symptoms not severe enough (i.e., MADRS < 15) at the baseline assessments
- Dementia, as defined by 3MS < 80 and clinical evidence of dementia
- Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, as diagnosed by the SCID
- Abuse of or dependence on alcohol or other substances within the past 3 months as determined by SCID, and score of > 8 on AUDIT-C and confirmed by study physician interview
- High risk for suicide (e.g., active SI and/or current/recent intent or plan) AND unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases
- Contraindication to venlafaxine or buprenorphine as determined by PCP and study physician including history of intolerance of either venlafaxine or buprenorphine in the study target dosage range (venlafaxine at up to 300 mg/day; buprenorphine at up to 1.2 mg/day)
- Inability to communicate in English (i.e., interview cannot be conducted without an interpreter; subject largely unable to understand questions and cannot respond in English)
- Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)
- Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. This will be determined based on information from the patient's personal physician and study physician's clinical judgment. Referral to the patient's personal physician or to a general practitioner will be made in these cases
- Subjects taking psychotropic medications that cannot be safely tapered and discontinued prior to study initiation. The following exceptions are allowed if they have been taken at a stable dose for at least 4 weeks prior to study entry and there is not a plan to change the dose during the next 32 -36 weeks: benzodiazepines up to 2 mg/d lorazepam equivalent; other sedative-hypnotics (e.g., zolpidem, zaleplon, eszopiclone); gabapentin if prescribed for non-psychiatric indication (e.g., neuropathy)
- History of opiate abuse or dependence
- Severe pain, defined as > 7 on 0-10 numeric rating scale for pain
- Concomitant use of strong or moderate CYP3A4 inhibitor (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketonazole, nefazodone, saquinovir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem)
- Refusal to stop all opioids (to avoid precipitating opioid withdrawal)
- Refusal to discontinue all alcohol (to reduce the risk of respiratory depression)
- Hepatic impairment (AST/ALT > 1.5 times upper normal)
- Estimated Glomerular Filtration Rate (GFR) < 20 ml/min
Inability/refusal to identify a person as an emergency contact
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Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: venlafaxine XR plus buprenorphine
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.
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slow titration to a maximum of 300 mg per day.
will remain on venlafaxine XR for upto 32 weeks.
Other Names:
randomized to either buprenorphine or placebo, dose range from 0.2 mg qd/ to 1.2 mg qd
Other Names:
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Placebo Comparator: venlafaxine XR plus placebo
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
|
slow titration to a maximum of 300 mg per day.
will remain on venlafaxine XR for upto 32 weeks.
Other Names:
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Montgomery-Asberg Depression Rating Scale
Time Frame: 32 weeks
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MADRS at baseline will establish study eligibility and will assess treatment-sensitive change in MDD.
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32 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Suicidal Ideation Scale ( SIS)
Time Frame: 32 weeks
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Assess suicidal ideation and previous suicide attempts
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32 weeks
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Brief Symptom Inventory for Anxiety
Time Frame: 32 weeks
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32 weeks
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Numeric Scale of Pain ( NRS-P)
Time Frame: 16 weeks
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16 weeks
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Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)
Time Frame: 16 weeks
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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
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16 weeks
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Antidepressant Side Effect Checklist (ASEC)
Time Frame: 16 weeks
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Assessment of side- effects
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16 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Daniel M Blumberger, MD, CAMH
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2014
Primary Completion (Actual)
January 19, 2017
Study Completion (Actual)
May 1, 2018
Study Registration Dates
First Submitted
October 8, 2014
First Submitted That Met QC Criteria
October 10, 2014
First Posted (Estimate)
October 13, 2014
Study Record Updates
Last Update Posted (Actual)
July 26, 2018
Last Update Submitted That Met QC Criteria
July 24, 2018
Last Verified
July 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Depression
- Depressive Disorder
- Depressive Disorder, Major
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Analgesics, Opioid
- Narcotics
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Antidepressive Agents
- Narcotic Antagonists
- Antidepressive Agents, Second-Generation
- Serotonin and Noradrenaline Reuptake Inhibitors
- Buprenorphine
- Venlafaxine Hydrochloride
Other Study ID Numbers
- 035/2014
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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