Major Depressive DisorderPhase 1/2IRLGreyBNCT02181231
Buprenorphine Used With Treatment Resistant Depression in Older Adults
A Phase 1/2 study testing venlafaxine XR and buprenorphine in people with Major Depressive Disorder and Depression, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The investigators are conducting a research study to learn about the safety and benefit of using a medication called buprenorphine for patients 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 XR and buprenorphine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2016to 30 Apr 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 > or = to 50 years.
- Major depressive disorder (MDD), single or recurrent, as diagnosed by the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID-IV).
- Montgomery Asberg Depression Rating Scale (MADRS) >/= to 15.
- Has or agrees to establish a clinical relationship with primary care physician (PCP).
- Availability of an informant (e.g., emergency contact).
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 Mini Mental State Exam (3MS) < 84 and clinical evidence of dementia (e.g., memory impairment, executive dysfunction, agnosia, apraxia, aphasia, with functional impairment).
- 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 confirmed by study physician interview.
- Drinking 15 or more drinks per week or consuming 5 or more drinks on any one occasion in the past week.
Show all 20Show fewer
- 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 XR or BPN as determined by PCP and study physician including history of intolerance of either venlafaxine XR or BPN in the study target dosage range (venlafaxine XR at up to 300 mg/day; BPN at up to 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 28 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 opioid 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, ketoconazole, nefazodone, saquinavir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem).
- Refusal to stop all opioids (to avoid precipitating opioid withdrawal).
- Hepatic impairment
- Estimated Glomerular Filtration Rate (GFR) < 20 ml/min.
- Inability/refusal to identify a person as an emergency contact.
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine
The investigators are conducting a research study to learn about the safety and benefit of using a medication called buprenorphine for patients 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 medications the investigators are using are: an anti-depressant medication called venlafaxine extended release (venlafaxine XR), which is 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 XR enhances treatment response.
Read the detailed description
We will consent approximately 100 participants, aged 50 and older, of both sexes and all races. Participation may last up to 32 weeks. We will utilize a clinical trial that has 3 Phases. In Phase 1 we will treat participants with an approximate 12 week course of open-label venlafaxine XR. This is the same lead-in treatment as in our ongoing "IRL Grey" ("Incomplete Response in Late Life Depression: Getting to Remission") multi-site R01 for late-life treatment resistant depression (LL-TRD), and we have found it to be highly successful. Participants who find relief from their depressive symptoms on venlafaxine XR alone will exit the study. Participants meeting criteria for an incomplete response (those still feeling depressed or withdrawn), will be randomly assigned to receive either low-dose buprenorphine or placebo augmentation of venlafaxine xr for 8 weeks (Phase 2), with the goal of achieving remission. Subjects will start at 0.2mg and titrate up as needed to 1.2mg. Subjects may undergo up to 2 MRI scans at the beginning and end of Phase 2 as well as cognitive testing at the same time points. At the conclusion of Phase 2, the blind will be broken for all participants. The participants who were on placebo will be able to begin taking buprenorphine immediately for Phase 3 (approximately 8 weeks). The participants who were already on buprenorphine in Phase 2 can continue to take it during Phase 3. Buprenorphine (BPN) will be tapered upon exiting the study, under the guidance of the P.I. The Phase 3 variations will allow all participants a chance to experience the benefits of buprenorphine (BPN). Efficacy and tolerability data will provide a clinically informative estimate of benefits and risks of buprenorphine augmentation for late-life treatment resistant depression (LL-TRD). We will randomize approximately 20 subjects into Phase 2. Additionally, we will collect buprenorphine (BPN) plasma levels on all those randomized to explore a dose-effect relationship on treatment response.
A small pilot study (ages 21 and up) of up to 15 healthy control subjects will be studied over an approximate 2 week period in order to ensure all of our procedures are working and to determine that there are clinical effects from buprenorphine. Control subjects will undergo a baseline PET/MRI before taking buprenorphine. At least 24 hours after the imaging, control subjects will receive a small dose of BPN starting at 0.2 mg/day and will titrate up as tolerated to 1.2 mg/day for the first week. Each subject will remain at approximately 1.2 mg/day for the duration of the study. At the end of the study, subjects will undergo a second PET/MRI.
- Conditions
- Major Depressive Disorder, Depression
- Being tested
- venlafaxine XR, buprenorphine, Placebo
- Keywords
- depression, older adult, buprenorphine, Effexor XR, treatment resistant, venlafaxine, Saint Louis, late life, major depression
- 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.
venlafaxine XRDrug
Also called Effexor XR
slow titration up to maximum dose of 300mg per day, will remain on venlafaxine XR for up to 32 weeks
buprenorphineDrug
Also called Temgesic, Subutex, Suboxone
randomized to either buprenorphine or placebo, dose range from 0.2 mg/ qd to 2mg/ qd
PlaceboDrug
patients will remain on venlafaxine XR and be randomized to receive either placebo or buprenorphine for 8 weeks. at the end of the 8 weeks those who did not receive buprenorphine will be offered the opportunity to try it.
| Study group | Role | What they receive |
|---|---|---|
| venlafaxine plus buprenorphine | Experimental | Drug: 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. 2 MRI sessions may occur before and during randomization. Receives: Drug: venlafaxine XR; Drug: buprenorphine |
| venlafaxine XR plus placebo | Placebo comparator | Drug: venlafaxine XR plus placebo Dosage varies. Subject remains on antidepressant throughout the 32 week study. Will be randomized to buprenorphine or placebo for up to 16 weeks. 2 MRI sessions may occur before and during randomization. Receives: Drug: venlafaxine XR; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale (MADRS)
Measure of depression severity, range of 0-60, with higher scores indicating more severe depression. We calculated the mean change in depression for both groups using baseline MADRS and week 8 MADRS scores.
Measured: Baseline and 8 weeks
Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)
Three item side effect scale used to assess frequency and intensity of side effects (range 0-6 for each item). We calculated the total score of all three items (range 0-18) with lower numbers indicating less frequency.
We calculated the mean score at baseline and week 8 (final timepoint).
Measured: Week 1 and week 8
Antidepressant Side Effect Checklist (ASEC)
Measure of side effects, consisting of 21 items, ranging from 0-3 (0 indicates no side effect, 3 indicates severe side effect). We calculated the total final score for the 21 items (total range is 0-63). A higher total number represents a greater severity in reported side effects. We calculated the mean change in side effects for both groups using baseline and 8 week data.
Measured: Baseline and 8 weeks
Secondary outcomes (3)
Suicide Ideation Scale (SIS)
A 19 item scale used to measure the presence or absence of suicidal ideations and the degree of severity of suicidal ideas. For this study, we computed the total score for all 19 items (total range 0-90). Higher scores represent a worse outcome. We also calculated the mean change in suicidal ideation for both groups using baseline and week 8 (final timepoint).
Measured: Baseline and 8 weeks
Brief Symptom Inventory-Anxiety Subscale (BSI)
Measure of anxiety. Six anxiety symptoms are rated based on how distressed the subject is for each symptom. The range for each symptom is 0-4, with 4 representing extreme distress. We computed the mean of the final BSI score (range 0-24), with a lower number indicating a better outcome. We also calculated the mean change in anxiety for both groups using baseline and Phase 2 week 8 (final time point) data.
Measured: Baseline and 8 weeks
Numeric Scale of Pain (NRS-P)
Measure used to assess pain, ranging from 0-10, with 10 being the worst possible pain.
We calculated the mean change in pain for both groups using baseline and week 8 (last time point).
Measured: Baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2014 (estimated)
- Study start1 Jun 2016
- Primary completion30 Apr 2018
- Study completion30 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Reckitt Benckiser LLC
- Responsible party
- Principal investigator, Eric Lenze, Washington University School of Medicine
- Investigators
- Eric J Lenze, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02181231
- Sponsor's protocol ID
- 201406016
- Other IDs
- IND 123020, IND 130774
- Acronym
- IRLGreyB
- Status last verified
- Jun 2019
- First submitted
- 1 Jul 2014
- Last updated
- 4 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2019. 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
- NCT02181231
- Acronym / sponsor ID
- IRLGreyB / 201406016
- Conditions
- Major Depressive Disorder, Depression
- Keywords
- depression, older adult, buprenorphine, Effexor XR, treatment resistant, venlafaxine, Saint Louis, late life
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Reckitt Benckiser LLC
- Study start
- 1 Jun 2016 (actual)
- Primary completion
- 30 Apr 2018 (actual)
- Study completion
- 30 Apr 2018 (actual)
- First posted
- 3 Jul 2014 (estimated)
- Results
- Posted 4 Jun 2019
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 patients 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 medications the investigators are using are: an anti-depressant medication called venlafaxine extended release (venlafaxine XR), which is 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 XR enhances treatment response.
Detailed description
We will consent approximately 100 participants, aged 50 and older, of both sexes and all races. Participation may last up to 32 weeks. We will utilize a clinical trial that has 3 Phases. In Phase 1 we will treat participants with an approximate 12 week course of open-label venlafaxine XR. This is the same lead-in treatment as in our ongoing "IRL Grey" ("Incomplete Response in Late Life Depression: Getting to Remission") multi-site R01 for late-life treatment resistant depression (LL-TRD), and we have found it to be highly successful. Participants who find relief from their depressive symptoms on venlafaxine XR alone will exit the study. Participants meeting criteria for an incomplete response (those still feeling depressed or withdrawn), will be randomly assigned to receive either low-dose buprenorphine or placebo augmentation of venlafaxine xr for 8 weeks (Phase 2), with the goal of achieving remission. Subjects will start at 0.2mg and titrate up as needed to 1.2mg. Subjects may undergo up to 2 MRI scans at the beginning and end of Phase 2 as well as cognitive testing at the same time points. At the conclusion of Phase 2, the blind will be broken for all participants. The participants who were on placebo will be able to begin taking buprenorphine immediately for Phase 3 (approximately 8 weeks). The participants who were already on buprenorphine in Phase 2 can continue to take it during Phase 3. Buprenorphine (BPN) will be tapered upon exiting the study, under the guidance of the P.I. The Phase 3 variations will allow all participants a chance to experience the benefits of buprenorphine (BPN). Efficacy and tolerability data will provide a clinically informative estimate of benefits and risks of buprenorphine augmentation for late-life treatment resistant depression (LL-TRD). We will randomize approximately 20 subjects into Phase 2. Additionally, we will collect buprenorphine (BPN) plasma levels on all those randomized to explore a dose-effect relationship on treatment response.
A small pilot study (ages 21 and up) of up to 15 healthy control subjects will be studied over an approximate 2 week period in order to ensure all of our procedures are working and to determine that there are clinical effects from buprenorphine. Control subjects will undergo a baseline PET/MRI before taking buprenorphine. At least 24 hours after the imaging, control subjects will receive a small dose of BPN starting at 0.2 mg/day and will titrate up as tolerated to 1.2 mg/day for the first week. Each subject will remain at approximately 1.2 mg/day for the duration of the study. At the end of the study, subjects will undergo a second PET/MRI.
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 plus buprenorphine | Experimental | Drug: venlafaxine XR, Drug: buprenorphineDrug: 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. 2 MRI sessions may occur before and during randomization. |
| venlafaxine XR plus placebo | Placebo comparator | Drug: venlafaxine XR, Drug: PlaceboDrug: venlafaxine XR plus placebo Dosage varies. Subject remains on antidepressant throughout the 32 week study. Will be randomized to buprenorphine or placebo for up to 16 weeks. 2 MRI sessions may occur before and during randomization. |
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 > or = to 50 years.
- Major depressive disorder (MDD), single or recurrent, as diagnosed by the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID-IV).
- Montgomery Asberg Depression Rating Scale (MADRS) >/= to 15.
- Has or agrees to establish a clinical relationship with primary care physician (PCP).
- Availability of an informant (e.g., emergency contact).
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 Mini Mental State Exam (3MS) < 84 and clinical evidence of dementia (e.g., memory impairment, executive dysfunction, agnosia, apraxia, aphasia, with functional impairment).
- 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 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 |
|---|---|---|
| venlafaxine XRAlso: Effexor XRslow titration up to maximum dose of 300mg per day, will remain on venlafaxine XR for up to 32 weeks | Drug | venlafaxine XR plus placebo, venlafaxine plus buprenorphine |
| buprenorphineAlso: Temgesic, Subutex, Suboxonerandomized to either buprenorphine or placebo, dose range from 0.2 mg/ qd to 2mg/ qd | Drug | venlafaxine plus buprenorphine |
| Placebopatients will remain on venlafaxine XR and be randomized to receive either placebo or buprenorphine for 8 weeks. at the end of the 8 weeks those who did not receive buprenorphine will be offered the opportunity to try it. | Drug | venlafaxine XR plus placebo |
Primary outcome
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Baseline and 8 weeks
Measure of depression severity, range of 0-60, with higher scores indicating more severe depression. We calculated the mean change in depression for both groups using baseline MADRS and week 8 MADRS scores.
Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)
Time frame: Week 1 and week 8
Three item side effect scale used to assess frequency and intensity of side effects (range 0-6 for each item). We calculated the total score of all three items (range 0-18) with lower numbers indicating less frequency. We calculated the mean score at baseline and week 8 (final timepoint).
Antidepressant Side Effect Checklist (ASEC)
Time frame: Baseline and 8 weeks
Measure of side effects, consisting of 21 items, ranging from 0-3 (0 indicates no side effect, 3 indicates severe side effect). We calculated the total final score for the 21 items (total range is 0-63). A higher total number represents a greater severity in reported side effects. We calculated the mean change in side effects for both groups using baseline and 8 week data.
3 secondary outcomes
Suicide Ideation Scale (SIS)
Time frame: Baseline and 8 weeks
Brief Symptom Inventory-Anxiety Subscale (BSI)
Time frame: Baseline and 8 weeks
Numeric Scale of Pain (NRS-P)
Time frame: Baseline and 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Eric J Lenze, MD principal investigator
Washington University School of Medicine
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 XR and buprenorphine in people with Major Depressive Disorder and Depression, run by Washington University School of Medicine at 1 site in United States.
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 4 Jun 2019. 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 United States. 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?
Yes. Results are posted in the registry (first posted 4 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: Baseline and 8 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Jun 2019.