Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine ((IRLGREY-B))
Primary Purpose
Major Depressive Disorder, Depression
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
venlafaxine
buprenorphine
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder
Eligibility Criteria
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
-
Sites / Locations
- Centre for Addiction and Mental Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
venlafaxine XR plus buprenorphine
venlafaxine XR plus placebo
Arm Description
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.
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
Outcomes
Primary Outcome Measures
The Montgomery-Asberg Depression Rating Scale
MADRS at baseline will establish study eligibility and will assess treatment-sensitive change in MDD.
Secondary Outcome Measures
Suicidal Ideation Scale ( SIS)
Assess suicidal ideation and previous suicide attempts
Brief Symptom Inventory for Anxiety
Numeric Scale of Pain ( NRS-P)
Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)
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
Antidepressant Side Effect Checklist (ASEC)
Assessment of side- effects
Full Information
NCT ID
NCT02263248
First Posted
October 8, 2014
Last Updated
July 24, 2018
Sponsor
Centre for Addiction and Mental Health
Collaborators
Reckitt Benckiser LLC
1. Study Identification
Unique Protocol Identification Number
NCT02263248
Brief Title
Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine
Acronym
(IRLGREY-B)
Official Title
Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
January 19, 2017 (Actual)
Study Completion Date
May 1, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre for Addiction and Mental Health
Collaborators
Reckitt Benckiser LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Depression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
venlafaxine XR plus buprenorphine
Arm Type
Experimental
Arm Description
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.
Arm Title
venlafaxine XR plus placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
venlafaxine
Other Intervention Name(s)
Effexor
Intervention Description
slow titration to a maximum of 300 mg per day. will remain on venlafaxine XR for upto 32 weeks.
Intervention Type
Drug
Intervention Name(s)
buprenorphine
Other Intervention Name(s)
Temgesic, Subutex, Suboxone
Intervention Description
randomized to either buprenorphine or placebo, dose range from 0.2 mg qd/ to 1.2 mg qd
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
The Montgomery-Asberg Depression Rating Scale
Description
MADRS at baseline will establish study eligibility and will assess treatment-sensitive change in MDD.
Time Frame
32 weeks
Secondary Outcome Measure Information:
Title
Suicidal Ideation Scale ( SIS)
Description
Assess suicidal ideation and previous suicide attempts
Time Frame
32 weeks
Title
Brief Symptom Inventory for Anxiety
Time Frame
32 weeks
Title
Numeric Scale of Pain ( NRS-P)
Time Frame
16 weeks
Title
Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)
Description
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
Time Frame
16 weeks
Title
Antidepressant Side Effect Checklist (ASEC)
Description
Assessment of side- effects
Time Frame
16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
-
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel M Blumberger, MD
Organizational Affiliation
CAMH
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Addiction and Mental Health
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6J1H4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
31846575
Citation
Buchalter ELF, Oughli HA, Lenze EJ, Dixon D, Miller JP, Blumberger DM, Karp JF, Reynolds CF 3rd, Mulsant BH. Predicting Remission in Late-Life Major Depression: A Clinical Algorithm Based Upon Past Treatment History. J Clin Psychiatry. 2019 Dec 10;80(6):18m12483. doi: 10.4088/JCP.18m12483.
Results Reference
derived
Learn more about this trial
Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine
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