Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Buprenorphine for Late-Life Treatment Resistant Depression (BUILD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01071538
Recruitment Status : Completed
First Posted : February 19, 2010
Results First Posted : March 17, 2016
Last Update Posted : March 9, 2018
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Reckitt Benckiser LLC
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Jordan F. Karp, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE February 17, 2010
First Posted Date  ICMJE February 19, 2010
Results First Submitted Date  ICMJE January 7, 2016
Results First Posted Date  ICMJE March 17, 2016
Last Update Posted Date March 9, 2018
Study Start Date  ICMJE May 2010
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2016)
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: February 18, 2010)
  • Montgomery Asberg Depression Rating Scale [ Time Frame: 16 weeks ]
  • Orthostatic blood pressure, Heart rate, and Respiratory rate [ Time Frame: 12 weeks ]
  • UKU Side Effect Rating Scale [ Time Frame: 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2016)
  • Brief Symptom Inventory -- Anxiety Subscale [ Time Frame: 8 weeks ]
    measure of anxiety Lower numbers indicate better outcome Theoretical Range 0-2.4
  • Positive and Negative Affect Scale [ Time Frame: 8 weeks ]
    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.
  • Pain Numeric Rating Scale (20 Item) [ Time Frame: 8 weeks ]
    measure of average physical pain score range 0-20 Higher scores indicate worse outcome
Original Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2010)
  • Brief Symptom Inventory -- Anxiety Subscale [ Time Frame: 16 weeks ]
  • Positive and Negative Affect Scale [ Time Frame: 16 weeks ]
  • Pain Numeric Rating Scale (20 Item) [ Time Frame: 16 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Buprenorphine for Late-Life Treatment Resistant Depression
Official Title  ICMJE Buprenorphine for Late-Life Treatment Resistant Depression
Brief 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.
Detailed Description

We are recruiting 20 participants for this pilot study. Subjects are recruited from either:

1) 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Depression
Intervention  ICMJE Drug: Buprenorphine
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 Arms  ICMJE Experimental: Buprenorphine
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.
Intervention: Drug: Buprenorphine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 25, 2012)
15
Original Estimated Enrollment  ICMJE
 (submitted: February 18, 2010)
20
Actual Study Completion Date  ICMJE May 2012
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01071538
Other Study ID Numbers  ICMJE BUILD
KL2RR024154 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jordan F. Karp, University of Pittsburgh
Study Sponsor  ICMJE University of Pittsburgh
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • Reckitt Benckiser LLC
  • National Center for Research Resources (NCRR)
Investigators  ICMJE
Principal Investigator: Jordan F Karp, M.D. University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP