Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine

NCT02176291 | Completed Phase 2 Results DMC

• 2 other identifiers: PRO13120236R34MH101371
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The purposes of this project are to examine the feasibility, safety, tolerability and clinical effect of low-dose buprenorphine as a novel treatment for late-life treatment-resistant depression and to develop preliminary data about mechanism of action.

Conditions

Depression; Major Depressive Disorder

Keywords

Buprenorphine; Receptors, opioid; Receptors, opioid kappa and mu

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  Measure of depression severity, range of 0-60 We calculated the mean change in depression severity for both groups using baseline MADRS and week 8 MADRS scores. Greater mean change represents better outcome.

  baseline and 8 weeks

Secondary Outcomes (1)

• Brief Symptom Inventory--Anxiety Subscale (BSI)

  Baseline and 8 weeks

Study Arms (2)

Buprenorphine

EXPERIMENTAL

Buprenorphine

Drug: Buprenorphine

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Buprenorphine DRUG

low-dose buprenorphine (range 0.2 mg/day -- 2.0 mg/day)

Also known as: suboxone, buprenex, temgesic, subutex

Buprenorphine

Placebo DRUG

matched placebo

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>/= to 50 years.
• Major depressive disorder (MDD), single or recurrent, as diagnosed by the Structured Clinical Interview for the DSM IV (SCID-IV).
• Montgomery-Åsberg 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).

You may not qualify if:

• Inability to provide informed consent.
• Depressive symptoms not severe enough i.e.,Montgomery-Åsberg Depression Rating Scale ( MADRS) \< 15 at the baseline assessments.
• Dementia, as defined by The Modified Mini-Mental State (3MS) examination \< 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 Structured Clinical Interview for DSM (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.
• Alcohol use amounting to 15 or more drinks per week or drinking 5 or more drinks on one occasion during any given week.
• High risk for suicide (e.g., active suicidal ideation (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 extended release (XR) or BPN as determined by 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, 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. Sodium and glucose levels done in the past 6 months are also reviewed before a subject begins study medication to determine if an illness is stable or uncontrolled. Individual lab parameters may deviate from normal without any associated pathophysiology or negative clinical affect; therefore we will follow the guide below before beginning starting any study medication.
• Sodium value of 135 but asymptomatic= consider to be normal and proceed without further testing.
• Sodium value of 134= repeat sodium. If value continues to be at 134 or higher and subject is asymptomatic, continue study participation but recheck sodium level after one week of exposure to study medication to confirm it has stayed stable.
• Sodium value of 133 or less= will evaluate subject's medication list to suggest possibly removing other medications which may be contributing to low sodium (in collaboration with their PCP), suggest fluid restriction and require repeat sodium that is normal range prior to commencing study.
• Glucose \< 275 and asymptomatic= stable to proceed but will communicate value to PCP with participants permission.

Sponsors & Collaborators

• Jordan F. Karp: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Western Psychiatric Institute and Clinic, University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Interventions

Buprenorphine; Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Naloxone; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Jordan F. Karp
• Organization: University of Pittsburgh

karpjf@upmc.edu

412-246-6048

Study Officials

• Jordan F. Karp, M.D.

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: June 27, 2014
• Study Start: August 1, 2014
• Primary Completion: April 1, 2017
• Study Completion: February 1, 2018
• Last Updated: August 29, 2018
• Results First Posted: July 2, 2018

Record last verified: 2018-08

Locations

US (1)