DepressionPhase 3BUP-TRDNCT01407575
Buprenorphine for Treatment Resistant Depression
A Phase 3 study testing Buprenorphine in people with Depression and Depressive Disorder, run by University of Pittsburgh at 1 site in United States.
Trial summary
The purpose of this study is to compare the safety and efficacy of buprenorphine with placebo for adults with treatment resistant depression (TRD). Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Depression, Depressive Disorder, Depressive Disorder, Major
- What is being tested?
- Buprenorphine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to Aug 2013
- Phase
- Phase 3
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 21 and older
- Major depressive disorder
- Non-responder to at least 2 FDA-approved antidepressants prescribed at a therapeutic dose, each for at least 6 weeks, or is a depression non-responder from an ongoing study of late-life depression at our research clinic.
- For women of child-bearing age, must have negative pregnancy test and agree not to get pregnant while participating.
Who cannot join
- Concomitant use of strong or moderate CYP3A4 inhibitor.
- Refusal to stop all opioids.
- Refusal to discontinue all alcohol.
- Refusal to discontinue benzodiazepines other than the equivalent of lorazepam 2 mg/day prescribed at a stable dose for at least the past 2 weeks.
- Hepatic impairment (AST/ALT > 1.5 times upper normal).
- Lung disease requiring supplemental oxygen (CPAP for sleep apnea is acceptable).
Show all 19Show fewer
- Estimated creatinine clearance <30 mL/min.
- Inability to provide informed consent.
- Depressive symptoms not severe enough (i.e., MADRS < 10) at the baseline assessment.
- Dementia, as defined by MMSE < 24 and clinical evidence of dementia
- Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
- Abuse of or dependence on alcohol or other substances within the past 3 months.
- Meets criteria for history of abuse or dependence upon opioids.
- High risk for suicide.
- Contraindication to buprenorphine.
- Inability to communicate in English.
- Non-correctable clinically significant sensory impairment.
- Unstable medical illness.
- Subjects taking psychotropic medications that cannot be safely tapered and discontinued prior to study initiation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Western Psychiatric Institute and Clinic, University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Buprenorphine For Treatment Resistant Depression
The purpose of this study is to compare the safety and efficacy of buprenorphine with placebo for adults with treatment resistant depression (TRD).
Read the detailed description
Rates of treatment resistant depression (TRD) in randomized controlled trials range from 50-80% using SSRIs and SNRIs. Innovative treatments are sorely needed. Modulation of the opiate system may be a novel treatment approach for TRD. Buprenorphine (BUP) is a partial agonist at mu-receptors, and also displays affinity for kappa and delta receptors. BUP has a favorable safety profile with low risk of respiratory depression, and the pharmacokinetics are not affected by advanced age or renal dysfunction. This combination of mu-agonism and kappa-antagonism produces less dysphoria than methadone, and animal studies suggest that kappa-antagonism may exert antidepressant effects. In this small proof of concept RCT (n=20), the investigators hypothesize that there will be differences between the group receiving buprenorphine and the group receiving placebo for the following: 1) depression, anxiety, and sleep, and 2)activation of the limbic system and brain structures rich in opiate receptors and critical to reward circuits. In addition, the investigators hypothesize that there will not be differences for measures of safety (vital signs, measures of memory and reaction time, and falls) between the two groups. This pilot project will provide compelling preliminary data to support a R01 application to test the efficacy of buprenorphine for these therapeutically challenging patients.
Specific Aims:
- Describe the relative safety of BUP in adults with TRD. The investigators hypothesize that there will be no differences in vital signs, measures of memory and reaction time, or falls between the two groups.
- Describe the clinical effect of BUP in adults with TRD. The investigators hypothesize that depression, anxiety, sleep, and health-related quality of life, will improve to a greater extent among those receiving BUP.
- Characterize the change in the phMRI responses to buprenorphine compared to placebo. The investigators will compare activation of the limbic system (rACC, insula, and amygdala) and brain structures rich in opiate receptors (periaqueductal grey) and critical to reward circuits (nucleus accumbens) before and immediately after administration of BUP or placebo.
The investigators are recruiting 20 community-dwelling adults, age 21 and older, who have tried at least two FDA-approved antidepressant medications at therapeutic doses each for at least 6 weeks during this episode of depression, and are still depressed.
- Conditions
- Depression, Depressive Disorder, Depressive Disorder, Major
- Being tested
- Buprenorphine, Placebo
- Keywords
- Buprenorphine, Receptors, opioid, Receptors, opioid, kappa
- Medical subject headings
- Depression, Depressive Disorder, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuprenorphineDrug
Also called suboxone, buprenex, temgesic, subutex
low-dose buprenorphine (range 0.2 mg/day -- 1.6 mg/day)
PlaceboDrug
matched placebo
| Study group | Role | What they receive |
|---|---|---|
| Buprenorphine | Experimental | 0.2 to 1.6mg of buprenorphine sublingual over the course of 8 weeks Receives: Drug: Buprenorphine |
| Placebo | Placebo comparator | matching placebo- sublingual- over the course of 8 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery Asberg Depression Rating Scale
measure of depression severity Theoretical Range 0-60 lower values represent better outcome
Measured: 6 weeks
Blood Pressure
Measure of systolic and diastolic blood pressure. 140/90 or lower is considered normal and indicates a better outcome.
Measured: 6 weeks
UKU Side Effect Rating Scale
measure of side effects 46 items with scores of 0,1,2,3 possible. Theoretical range 0-138 Lower scores indicate fewer side effects
Measured: 6 weeks
Heart Rate
Heart Rate (Beats per minute) 60-100 beats per minute is considered normal lower heart rate represent healthier outcome
Measured: 6 weeks
Weight
Participant weight
Measured: 6 weeks
Secondary outcomes (2)
Brief Symptom Inventory -- Anxiety Subscale
measure of anxiety Lower numbers indicate better outcome Theoretical Range 0-2.4
Measured: 6 weeks
Positive and Negative Affect Scale
Positive Affect Score: Scores can range from 10 - 50, with higher scores representing higher levels of positive affect.
Negative Affect Score: Scores can range from 10 - 50, with lower scores representing lower levels of negative affect.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2011 (estimated)
- Study startSep 2011
- Primary completionAug 2013
- Study completionAug 2013
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 DepressionStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Responsible party
- Principal investigator, Jordan F. Karp, University of Pittsburgh
- Investigators
- Jordan F Karp, M.D., Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01407575
- Sponsor's protocol ID
- BUP-TRD
- Acronym
- BUP-TRD
- Status last verified
- Feb 2018
- First submitted
- 29 Jul 2011
- Last updated
- 9 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Buprenorphine For Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT01407575
- Acronym / sponsor ID
- BUP-TRD / BUP-TRD
- Conditions
- Depression, Depressive Disorder, Depressive Disorder, Major
- Keywords
- Buprenorphine, Receptors, opioid, Receptors, opioid, kappa
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Alliance for Research on Schizophrenia and Depression
- Study start
- Sep 2011
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 2 Aug 2011 (estimated)
- Results
- Posted 17 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the safety and efficacy of buprenorphine with placebo for adults with treatment resistant depression (TRD).
Detailed description
Rates of treatment resistant depression (TRD) in randomized controlled trials range from 50-80% using SSRIs and SNRIs. Innovative treatments are sorely needed. Modulation of the opiate system may be a novel treatment approach for TRD. Buprenorphine (BUP) is a partial agonist at mu-receptors, and also displays affinity for kappa and delta receptors. BUP has a favorable safety profile with low risk of respiratory depression, and the pharmacokinetics are not affected by advanced age or renal dysfunction. This combination of mu-agonism and kappa-antagonism produces less dysphoria than methadone, and animal studies suggest that kappa-antagonism may exert antidepressant effects. In this small proof of concept RCT (n=20), the investigators hypothesize that there will be differences between the group receiving buprenorphine and the group receiving placebo for the following: 1) depression, anxiety, and sleep, and 2)activation of the limbic system and brain structures rich in opiate receptors and critical to reward circuits. In addition, the investigators hypothesize that there will not be differences for measures of safety (vital signs, measures of memory and reaction time, and falls) between the two groups. This pilot project will provide compelling preliminary data to support a R01 application to test the efficacy of buprenorphine for these therapeutically challenging patients.
Specific Aims:
- Describe the relative safety of BUP in adults with TRD. The investigators hypothesize that there will be no differences in vital signs, measures of memory and reaction time, or falls between the two groups.
- Describe the clinical effect of BUP in adults with TRD. The investigators hypothesize that depression, anxiety, sleep, and health-related quality of life, will improve to a greater extent among those receiving BUP.
- Characterize the change in the phMRI responses to buprenorphine compared to placebo. The investigators will compare activation of the limbic system (rACC, insula, and amygdala) and brain structures rich in opiate receptors (periaqueductal grey) and critical to reward circuits (nucleus accumbens) before and immediately after administration of BUP or placebo.
The investigators are recruiting 20 community-dwelling adults, age 21 and older, who have tried at least two FDA-approved antidepressant medications at therapeutic doses each for at least 6 weeks during this episode of depression, and are still depressed.
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 |
|---|---|---|
| Buprenorphine | Experimental | Drug: Buprenorphine0.2 to 1.6mg of buprenorphine sublingual over the course of 8 weeks |
| Placebo | Placebo comparator | Drug: Placebomatching placebo- sublingual- over the course of 8 weeks |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 21 and older
- Major depressive disorder
- Non-responder to at least 2 FDA-approved antidepressants prescribed at a therapeutic dose, each for at least 6 weeks, or is a depression non-responder from an ongoing study of late-life depression at our research clinic.
- For women of child-bearing age, must have negative pregnancy test and agree not to get pregnant while participating.
Key exclusion criteria (19 listed)
- Concomitant use of strong or moderate CYP3A4 inhibitor.
- Refusal to stop all opioids.
- Refusal to discontinue all alcohol.
- Refusal to discontinue benzodiazepines other than the equivalent of lorazepam 2 mg/day prescribed at a stable dose for at least the past 2 weeks.
- Hepatic impairment (AST/ALT > 1.5 times upper normal).
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 |
|---|---|---|
| BuprenorphineAlso: suboxone, buprenex, temgesic, subutexlow-dose buprenorphine (range 0.2 mg/day -- 1.6 mg/day) | Drug | Buprenorphine |
| Placebomatched placebo | Drug | Placebo |
Primary outcome
Montgomery Asberg Depression Rating Scale
Time frame: 6 weeks
measure of depression severity Theoretical Range 0-60 lower values represent better outcome
Blood Pressure
Time frame: 6 weeks
Measure of systolic and diastolic blood pressure. 140/90 or lower is considered normal and indicates a better outcome.
UKU Side Effect Rating Scale
Time frame: 6 weeks
measure of side effects 46 items with scores of 0,1,2,3 possible. Theoretical range 0-138 Lower scores indicate fewer side effects
Heart Rate
Time frame: 6 weeks
Heart Rate (Beats per minute) 60-100 beats per minute is considered normal lower heart rate represent healthier outcome
Weight
Time frame: 6 weeks
Participant weight
2 secondary outcomes
Brief Symptom Inventory -- Anxiety Subscale
Time frame: 6 weeks
Positive and Negative Affect Scale
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Jordan F Karp, M.D. principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Buprenorphine in people with Depression and Depressive Disorder, run by University of Pittsburgh 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 4 inclusion and 19 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 9 Mar 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 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 17 Mar 2016). 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 (time frame: 6 weeks). The study lists 5 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 9 Mar 2018.