DepressionPhase 2BUILDNCT01071538
Buprenorphine for Late-Life Treatment Resistant Depression
A Phase 2 study testing Buprenorphine in people with Depression, run by University of Pittsburgh at 1 site in United States.
Trial summary
The goals of this pilot study are to gather data about the safety and clinical effect of low-dose buprenorphine in older adults with treatment resistant depression. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Depression
- What is being tested?
- Buprenorphine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to May 2012
- Phase
- Phase 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 >/= 50 years
- 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.
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.
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.
- 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 Clinica, University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, 15213
About this study
The goals of this pilot study are to gather data about the safety and clinical effect of low-dose buprenorphine in older adults with treatment resistant depression.
Read the detailed description
We are recruiting 20 participants for this pilot study. Subjects are recruited from either:
- An ongoing study of Late-Life Depression(MH083660; PI: Reynolds) who did not meet research response criteria; and 2) community-dwelling individuals, at least 50 years old, who have tried at least two FDA-approved antidepressant medications at therapeutic doses each for at least 6 weeks, and who are currently in an episode of major depression.
Overview of intervention: To guide future placebo-controlled work, at this preliminary stage of research we will collect data about both buprenorphine (BUP) 1) augmentation pharmacotherapy, and 2) monotherapy. Subjects recruited from the community will have the buprenorphine prescribed as augmentation to any currently prescribed antidepressant medication.
BUP 0.2 mg will be used for the first week. The first dose will be administered at the clinic under the supervision of the PI. Because peak plasma levels occur 60 minutes after ingestion, subjects will be re-assessed after 1 hour for safety. Participants will be seen weekly for eight weeks to assess progress and monitor intervention-emergent side effects. Dosing increases will be guided by antidepressant response (e.g., continued MADRS scores > 10 will trigger an increase dose of BUP) and our protocolized use of the Frequency, Intensity, and Burden of Side Effect Rating (FIBSER) Scale score. For example, a score of 5 to 7 on the FIBSER will trigger additional assessment of side effects and require justification for increasing the dose, while a score of > 7 will signal no increase in dose, although specific side effects should be reviewed in detail before a final determination, including review if the UKU Side Effects Rating Scale.
We will increase the dose by 0.2 mg/week up to 1.6 mg/day based on MADRS and FIBSER scores. Every time the dose is increased, the first ingestion of the higher dose will be monitored in the clinic as described above.
Subjects will participate in the project at the Late-Life Depression Clinic on the 7th Floor of Bellefield Tower. Subjects will complete paper and pencil and clinician-administered psychiatric assessments before receiving the first dose of buprenorphine and at all subsequent visits. After the first ingestion and all subsequent first ingestions of higher doses of BUP, subjects will remain in the clinic for 60 minutes after ingestion and be re-assessed for the emergence of side effects and have vital signs re-checked. The duration of the first visit will be approximately 2.5 hours. If subsequent visits require observed ingestion of buprenorphine, they will last about 1.75 hours. If subsequent visits do not require observed ingestion of buprenorphine, these visits will last 30-45 minutes.
Prior to the first ingestion, the first ingestion of subsequent higher doses, and at study end, subjects will complete a 15 minute battery of computerized neuropsychological tests assessing reaction time and attention. These tests will be repeated 60 minutes after the ingestion. Prior to the first ingestion and after discontinuation of the buprenorphine, memory will be assessed with the Hopkins Verbal Learning Test (HVLT). The HVLT takes about 10 minutes to complete.
The discontinuation phase will occur during weeks 9-12. To minimize the risk of withdrawal symptoms, we will discontinue the buprenorphine slowly by reducing the dose to 0.4 mg/day for 7 days, then 0.2 mg/day every other day for 7 days, and then stop the buprenorphine. We will see subjects weekly over these four weeks.
The final visit will occur at week 16. This will be a telephone check in of mood and functioning. This call will take about 15-20 minutes.
- Conditions
- Depression
- Being tested
- Buprenorphine
- Keywords
- Depressive Disorder, Major, Late-Life Depression, Geriatrics, Buprenorphine
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuprenorphineDrug
Sublingual buprenorphine 0.2 mg will be used for the first week. The dose will be increased by 0.2 mg/week based on safety and clinical response up to a maximal dose of 1.6 mg/day.
| Study group | Role | What they receive |
|---|---|---|
| Buprenorphine | Experimental | Older adults with treatment resistant depression will receive buprenorphine up to 1.6 mg/day for 8 weeks. Discontinuation of the buprenorphine will occur during weeks 9-12. Receives: Drug: Buprenorphine |
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 scale range 0-60 Lower values represent better outcome
Measured: 8 weeks
Blood Pressure
Blood Pressure- systolic and diastolic 140/90 or lower is considered normal and indicates a better outcome.
Measured: 8 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: 8 weeks
Heart Rate
Heart Rate (Beats per minute) 60-100 beats per minute is considered normal lower heart rate represent healthier outcome
Measured: 8 weeks
Secondary outcomes (3)
Brief Symptom Inventory -- Anxiety Subscale
measure of anxiety Lower numbers indicate better outcome Theoretical Range 0-2.4
Measured: 8 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: 8 weeks
Pain Numeric Rating Scale (20 Item)
measure of average physical pain score range 0-20 Higher scores indicate worse outcome
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2010 (estimated)
- Study startMay 2010
- Primary completionMay 2012
- Study completionMay 2012
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.
- Publications (5)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Reckitt Benckiser LLC, National Center for Research Resources (NCRR)
- 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
- NCT01071538
- Sponsor's protocol ID
- BUILD
- Other IDs
- KL2RR024154
- Acronym
- BUILD
- Status last verified
- Feb 2018
- First submitted
- 17 Feb 2010
- Last updated
- 9 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Mague SD, Pliakas AM, Todtenkopf MS, Tomasiewicz HC, Zhang Y, Stevens WC Jr, Jones RM, Portoghese PS, Carlezon WA Jr. Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. J Pharmacol Exp Ther. 2003 Apr;305(1):323-30. doi: 10.1124/jpet.102.046433.
PubMed 12649385Nyhuis PW, Gastpar M, Scherbaum N. Opiate treatment in depression refractory to antidepressants and electroconvulsive therapy. J Clin Psychopharmacol. 2008 Oct;28(5):593-5. doi: 10.1097/JCP.0b013e31818638a4. No abstract available.
PubMed 18794671Bodkin JA, Zornberg GL, Lukas SE, Cole JO. Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995 Feb;15(1):49-57. doi: 10.1097/00004714-199502000-00008.
PubMed 7714228Emrich HM, Vogt P, Herz A. Possible antidepressive effects of opioids: action of buprenorphine. Ann N Y Acad Sci. 1982;398:108-12. doi: 10.1111/j.1749-6632.1982.tb39483.x. No abstract available.
PubMed 6760767Karp JF, Butters MA, Begley AE, Miller MD, Lenze EJ, Blumberger DM, Mulsant BH, Reynolds CF 3rd. Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults. J Clin Psychiatry. 2014 Aug;75(8):e785-93. doi: 10.4088/JCP.13m08725.
PubMed 25191915
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 Late-Life Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT01071538
- Acronym / sponsor ID
- BUILD / BUILD
- Conditions
- Depression
- Keywords
- Depressive Disorder, Major, Late-Life Depression, Geriatrics, Buprenorphine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Reckitt Benckiser LLC, National Center for Research Resources (NCRR)
- Study start
- May 2010
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 19 Feb 2010 (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 goals of this pilot study are to gather data about the safety and clinical effect of low-dose buprenorphine in older adults with treatment resistant depression.
Detailed description
We are recruiting 20 participants for this pilot study. Subjects are recruited from either:
- An ongoing study of Late-Life Depression(MH083660; PI: Reynolds) who did not meet research response criteria; and 2) community-dwelling individuals, at least 50 years old, who have tried at least two FDA-approved antidepressant medications at therapeutic doses each for at least 6 weeks, and who are currently in an episode of major depression.
Overview of intervention: To guide future placebo-controlled work, at this preliminary stage of research we will collect data about both buprenorphine (BUP) 1) augmentation pharmacotherapy, and 2) monotherapy. Subjects recruited from the community will have the buprenorphine prescribed as augmentation to any currently prescribed antidepressant medication.
BUP 0.2 mg will be used for the first week. The first dose will be administered at the clinic under the supervision of the PI. Because peak plasma levels occur 60 minutes after ingestion, subjects will be re-assessed after 1 hour for safety. Participants will be seen weekly for eight weeks to assess progress and monitor intervention-emergent side effects. Dosing increases will be guided by antidepressant response (e.g., continued MADRS scores > 10 will trigger an increase dose of BUP) and our protocolized use of the Frequency, Intensity, and Burden of Side Effect Rating (FIBSER) Scale score. For example, a score of 5 to 7 on the FIBSER will trigger additional assessment of side effects and require justification for increasing the dose, while a score of > 7 will signal no increase in dose, although specific side effects should be reviewed in detail before a final determination, including review if the UKU Side Effects Rating Scale.
We will increase the dose by 0.2 mg/week up to 1.6 mg/day based on MADRS and FIBSER scores. Every time the dose is increased, the first ingestion of the higher dose will be monitored in the clinic as described above.
Subjects will participate in the project at the Late-Life Depression Clinic on the 7th Floor of Bellefield Tower. Subjects will complete paper and pencil and clinician-administered psychiatric assessments before receiving the first dose of buprenorphine and at all subsequent visits. After the first ingestion and all subsequent first ingestions of higher doses of BUP, subjects will remain in the clinic for 60 minutes after ingestion and be re-assessed for the emergence of side effects and have vital signs re-checked. The duration of the first visit will be approximately 2.5 hours. If subsequent visits require observed ingestion of buprenorphine, they will last about 1.75 hours. If subsequent visits do not require observed ingestion of buprenorphine, these visits will last 30-45 minutes.
Prior to the first ingestion, the first ingestion of subsequent higher doses, and at study end, subjects will complete a 15 minute battery of computerized neuropsychological tests assessing reaction time and attention. These tests will be repeated 60 minutes after the ingestion. Prior to the first ingestion and after discontinuation of the buprenorphine, memory will be assessed with the Hopkins Verbal Learning Test (HVLT). The HVLT takes about 10 minutes to complete.
The discontinuation phase will occur during weeks 9-12. To minimize the risk of withdrawal symptoms, we will discontinue the buprenorphine slowly by reducing the dose to 0.4 mg/day for 7 days, then 0.2 mg/day every other day for 7 days, and then stop the buprenorphine. We will see subjects weekly over these four weeks.
The final visit will occur at week 16. This will be a telephone check in of mood and functioning. This call will take about 15-20 minutes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Buprenorphine | Experimental | Drug: BuprenorphineOlder adults with treatment resistant depression will receive buprenorphine up to 1.6 mg/day for 8 weeks. Discontinuation of the buprenorphine will occur during weeks 9-12. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age >/= 50 years
- 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.
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 |
|---|---|---|
| BuprenorphineSublingual buprenorphine 0.2 mg will be used for the first week. The dose will be increased by 0.2 mg/week based on safety and clinical response up to a maximal dose of 1.6 mg/day. | Drug | Buprenorphine |
Primary outcome
Montgomery Asberg Depression Rating Scale
Time frame: 8 weeks
measure of depression severity theoretical scale range 0-60 Lower values represent better outcome
Blood Pressure
Time frame: 8 weeks
Blood Pressure- systolic and diastolic 140/90 or lower is considered normal and indicates a better outcome.
UKU Side Effect Rating Scale
Time frame: 8 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: 8 weeks
Heart Rate (Beats per minute) 60-100 beats per minute is considered normal lower heart rate represent healthier outcome
3 secondary outcomes
Brief Symptom Inventory -- Anxiety Subscale
Time frame: 8 weeks
Positive and Negative Affect Scale
Time frame: 8 weeks
Pain Numeric Rating Scale (20 Item)
Time frame: 8 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.
- Background: PubMed 12649385Mague SD, Pliakas AM, Todtenkopf MS, Tomasiewicz HC, Zhang Y, Stevens WC Jr, Jones RM, Portoghese PS, Carlezon WA Jr. Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. J Pharmacol Exp Ther. 2003 Apr;305(1):323-30. doi: 10.1124/jpet.102.046433.
- Background: PubMed 18794671Nyhuis PW, Gastpar M, Scherbaum N. Opiate treatment in depression refractory to antidepressants and electroconvulsive therapy. J Clin Psychopharmacol. 2008 Oct;28(5):593-5. doi: 10.1097/JCP.0b013e31818638a4. No abstract available.
- Background: PubMed 7714228Bodkin JA, Zornberg GL, Lukas SE, Cole JO. Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995 Feb;15(1):49-57. doi: 10.1097/00004714-199502000-00008.
- Background: PubMed 6760767Emrich HM, Vogt P, Herz A. Possible antidepressive effects of opioids: action of buprenorphine. Ann N Y Acad Sci. 1982;398:108-12. doi: 10.1111/j.1749-6632.1982.tb39483.x. No abstract available.
- Derived from this study: PubMed 25191915Karp JF, Butters MA, Begley AE, Miller MD, Lenze EJ, Blumberger DM, Mulsant BH, Reynolds CF 3rd. Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults. J Clin Psychiatry. 2014 Aug;75(8):e785-93. doi: 10.4088/JCP.13m08725.
- This link describes our other work with late-life depression at our NIH-funded research clinic in Pittsburgh, PALink provided by the sponsor.
- 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 2 study testing Buprenorphine in people with Depression, 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 3 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. 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 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 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: 8 weeks). The study lists 4 primary outcomes in all. 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 NCT01071538, which also lists 5 linked publications.
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.