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

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

    • Ontario
      • Toronto, Ontario, Canada, M6J1H4
        • Centre for Addiction and Mental Health

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:

  1. Age > 50 years
  2. Major depressive disorder (MDD), single or recurrent, as diagnosed by the SCID-IV (or SCID-5 if available)
  3. MADRS > 15
  4. Has or agrees to establish a clinical relationship with primary care physician (PCP).
  5. Availability of an informant (e.g., emergency contact) is encouraged but not required for study participation

Exclusion Criteria:

  1. Inability to provide informed consent
  2. Depressive symptoms not severe enough (i.e., MADRS < 15) at the baseline assessments
  3. Dementia, as defined by 3MS < 80 and clinical evidence of dementia
  4. Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, as diagnosed by the SCID
  5. 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
  6. 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
  7. 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)
  8. 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)
  9. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview)
  10. 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
  11. 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)
  12. History of opiate abuse or dependence
  13. Severe pain, defined as > 7 on 0-10 numeric rating scale for pain
  14. Concomitant use of strong or moderate CYP3A4 inhibitor (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketonazole, nefazodone, saquinovir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem)
  15. Refusal to stop all opioids (to avoid precipitating opioid withdrawal)
  16. Refusal to discontinue all alcohol (to reduce the risk of respiratory depression)
  17. Hepatic impairment (AST/ALT > 1.5 times upper normal)
  18. Estimated Glomerular Filtration Rate (GFR) < 20 ml/min
  19. Inability/refusal to identify a person as an emergency contact

    -

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
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.
slow titration to a maximum of 300 mg per day. will remain on venlafaxine XR for upto 32 weeks.
Other Names:
  • Effexor
randomized to either buprenorphine or placebo, dose range from 0.2 mg qd/ to 1.2 mg qd
Other Names:
  • Subutex
  • Suboxone
  • Temgesic
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:
  • Effexor
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Montgomery-Asberg Depression Rating Scale
Time Frame: 32 weeks
MADRS at baseline will establish study eligibility and will assess treatment-sensitive change in MDD.
32 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Suicidal Ideation Scale ( SIS)
Time Frame: 32 weeks
Assess suicidal ideation and previous suicide attempts
32 weeks
Brief Symptom Inventory for Anxiety
Time Frame: 32 weeks
32 weeks
Numeric Scale of Pain ( NRS-P)
Time Frame: 16 weeks
16 weeks
Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)
Time Frame: 16 weeks
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
16 weeks
Antidepressant Side Effect Checklist (ASEC)
Time Frame: 16 weeks
Assessment of side- effects
16 weeks

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

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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