Trial record 5 of 133 for:    depression pittsburgh | Open Studies

Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine (IRLGREY-B)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by University of Pittsburgh
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Jordan F. Karp, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT02176291
First received: June 25, 2014
Last updated: August 10, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Depression
Major Depressive Disorder
Drug: Buprenorphine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: up to 32 weeks ] [ Designated as safety issue: No ]
    depression scale designed to be sensitive to change

  • fMRI changes in response to exposure to buprenorphine or placebo [ Time Frame: before and after 3 weeks exposure to buprenorphine or placebo ] [ Designated as safety issue: No ]
    we will explore changes in limbic and reward networks as a function of exposure to buprenorphine or placebo and correlate changes with clinical response.


Secondary Outcome Measures:
  • Positive and Negative Affect Scale [ Time Frame: up to 32 weeks ] [ Designated as safety issue: No ]
  • Side-effect rating scale (FIBSER) [ Time Frame: up to 32 weeks ] [ Designated as safety issue: Yes ]
  • Brief Symptom Inventory--Anxiety Subscale (BSI) [ Time Frame: up to 32 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: August 2014
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Buprenorphine
Buprenorphine
Drug: Buprenorphine
low-dose buprenorphine (range 0.2 mg/day -- 2.0 mg/day)
Other Names:
  • suboxone
  • buprenex
  • temgesic
  • subutex
Placebo Comparator: Placebo
Placebo
Drug: Placebo
matched placebo

Detailed Description:

Up to one half of older patients with major depression develop Late-Life Treatment Resistant Depression (LL-TRD). Consequences of LL-TRD include suicide, worsened medical conditions, increased caregiver burden, and higher all-cause mortality. The development and testing of novel-mechanism pharmacotherapies is a public health priority embraced by NIMH. Among the neuropeptidergic transmitters, opioids are known to modulate mood, and this system is often altered in patients with major depression. Targeting the opiate system in LL-TRD may positively modulate a system in which there is age-associated imbalance between circulating opiates and the density and binding affinity of mu and kappa opiate receptors. Buprenorphine (BPN) is an antagonist at the kappa opiate receptor and a partial agonist at the mu opiate receptor. Either, or both, of these pharmacodynamic actions may underlie its putative antidepressant effects. Our research group has open pilot data from 15 older adults with prospectively demonstrated treatment resistance to venlafaxine who were exposed to low-dose BPN, suggesting a clinically meaningful antidepressant effect. In addition, since BPN: 1) is available in sublingual formulation and 2) has a favorable safety and pharmacokinetic profile, it is an attractive candidate to re-purpose as a molecule for LL-TRD. Thus, the overarching aims of this project are to examine the feasibility, safety, tolerability and clinical effect of low-dose BPN as a novel treatment for LL-TRD and to develop preliminary data about mechanism of action (MOA).

The overarching aims are to examine the feasibility, safety, and tolerability of buprenorphine (BPN) as a novel treatment for late-life treatment resistant depression (LL-TRD). This also involves using translational tools of modern neurobiology (fMRI) to rapidly obtain proof-of-concept support for further clinical development. Formal dosing schedules in the use of buprenorphine have yet to be thoroughly established. This study hopes to determine optimal dosing strategies to improve acceptability.

  Eligibility

Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 50 and older
  • Major depressive disorder
  • MADRS rating greater than or equal to 15
  • Has or agrees to establish a clinical relationship with primary care physician (PCP).
  • Availability of an informant (e.g., emergency contact)

Exclusion Criteria:

  • Inability to provide informed consent.
  • Depressive symptoms not severe enough (i.e., MADRS < 15) at the baseline assessments.
  • Dementia, as defined by 3MS < 80 and clinical evidence of dementia.
  • 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.
  • 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 opiate 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, ketonazole, nefazodone, saquinovir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem)
  • Refusal to stop all opioids (to avoid precipitating opioid withdrawal).
  • Refusal to discontinue all alcohol (to reduce the risk of respiratory depression).
  • Hepatic impairment (AST/ALT > 1.5 times upper normal).
  • Estimated Glomerular Filtration Rate (GFR) < 20 ml/min.
  • Inability/refusal to identify a person as an emergency contact.
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02176291

Contacts
Contact: Sunita Chickering, M.A. LPC 412-246-6021 chickeringsn@upmc.edu
Contact: Jackie Stack, M.S.N. 412-246-6016 stackja@upmc.edu

Locations
United States, Pennsylvania
Western Psychiatric Institute and Clinic, University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Sunita Chickering, M.A. LPC    412-246-6021    chickeringsn@upmc.edu   
Contact: Jackie Stack, M.S.N.    412-246-6016    stackja@upmc.edu   
Principal Investigator: Jordan F. Karp, M.D.         
Sponsors and Collaborators
Jordan F. Karp
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Jordan F. Karp, M.D. University of Pittsburgh
  More Information

Responsible Party: Jordan F. Karp, Associate Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02176291     History of Changes
Other Study ID Numbers: PRO13120236  R34MH101371 
Study First Received: June 25, 2014
Last Updated: August 10, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by University of Pittsburgh:
Buprenorphine
Receptors, opioid
Receptors, opioid kappa and mu

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Buprenorphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists

ClinicalTrials.gov processed this record on August 24, 2016