Major Depressive DisorderPhase 1/2(IRLGREY-B)NCT02263248
Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine
A Phase 1/2 study testing venlafaxine and buprenorphine in people with Major Depressive Disorder and Depression, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial 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 . Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Major Depressive Disorder, Depression
- What is being tested?
- venlafaxine and buprenorphine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2014to 1 May 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
- -
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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).
- Conditions
- Major Depressive Disorder, Depression
- Being tested
- venlafaxine, buprenorphine, placebo
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
venlafaxineDrug
Also called Effexor
slow titration to a maximum of 300 mg per day. will remain on venlafaxine XR for upto 32 weeks.
buprenorphineDrug
Also called Temgesic, Subutex, Suboxone
randomized to either buprenorphine or placebo, dose range from 0.2 mg qd/ to 1.2 mg qd
placeboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| venlafaxine XR plus buprenorphine | Experimental | 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. Receives: Drug: venlafaxine; Drug: buprenorphine |
| venlafaxine XR plus placebo | Placebo comparator | 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 Receives: Drug: venlafaxine; Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Montgomery-Asberg Depression Rating Scale
MADRS at baseline will establish study eligibility and will assess treatment-sensitive change in MDD.
Measured: 32 weeks
Secondary outcomes (5)
Suicidal Ideation Scale ( SIS)
Assess suicidal ideation and previous suicide attempts
Measured: 32 weeks
Brief Symptom Inventory for Anxiety
Measured: 32 weeks
Numeric Scale of Pain ( NRS-P)
Measured: 16 weeks
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
Measured: 16 weeks
Antidepressant Side Effect Checklist (ASEC)
Assessment of side- effects
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2014 (estimated)
- Study startDec 2014
- Primary completion19 Jan 2017
- Study completion1 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Reckitt Benckiser LLC
- Responsible party
- Principal investigator, Daniel Blumberger, Centre for Addiction and Mental Health
- Investigators
- Daniel M Blumberger, MD, Principal investigator, CAMH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02263248
- Sponsor's protocol ID
- 035/2014
- Acronym
- (IRLGREY-B)
- Status last verified
- Jul 2018
- First submitted
- 8 Oct 2014
- Last updated
- 26 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 31846575
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine
- ClinicalTrials.gov ID
- NCT02263248
- Acronym / sponsor ID
- (IRLGREY-B) / 035/2014
- Conditions
- Major Depressive Disorder, Depression
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Reckitt Benckiser LLC
- Study start
- Dec 2014
- Primary completion
- 19 Jan 2017 (actual)
- Study completion
- 1 May 2018 (actual)
- First posted
- 13 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| venlafaxine XR plus buprenorphine | Experimental | Drug: venlafaxine, Drug: buprenorphineDrug 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. |
| venlafaxine XR plus placebo | Placebo comparator | Drug: venlafaxine, Drug: placeboDrug 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 |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| venlafaxineAlso: Effexorslow titration to a maximum of 300 mg per day. will remain on venlafaxine XR for upto 32 weeks. | Drug | venlafaxine XR plus buprenorphine, venlafaxine XR plus placebo |
| buprenorphineAlso: Temgesic, Subutex, Suboxonerandomized to either buprenorphine or placebo, dose range from 0.2 mg qd/ to 1.2 mg qd | Drug | venlafaxine XR plus buprenorphine |
| placebopatients 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. | Drug | venlafaxine XR plus placebo |
Primary outcome
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.
5 secondary outcomes
Suicidal Ideation Scale ( SIS)
Time frame: 32 weeks
Brief Symptom Inventory for Anxiety
Time frame: 32 weeks
Numeric Scale of Pain ( NRS-P)
Time frame: 16 weeks
Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)
Time frame: 16 weeks
Antidepressant Side Effect Checklist (ASEC)
Time frame: 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2018.
- Derived from this study: PubMed 31846575Buchalter 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel M Blumberger, MD principal investigator
CAMH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing venlafaxine and buprenorphine in people with Major Depressive Disorder and Depression, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Montgomery-Asberg Depression Rating Scale (time frame: 32 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02263248, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2018.