Efficacy of Buprenorphine and XR-Naltrexone Combination for Relapse Prevention in Opioid Use Disorder

New York State Psychiatric Institute2 sites in 1 country180 target enrollmentApril 18, 2023

ConditionsOpioid-use Disorder

InterventionsBuprenorphine/naloxone Placebo

DrugsBuprenorphine/naloxone Placebo

Overview

Phase: Phase 2
Intervention: Buprenorphine/naloxone
Conditions: Opioid-use Disorder
Sponsor: New York State Psychiatric Institute
Enrollment: 180
Locations: 2
Primary Endpoint: Proportion of participants receiving XR-naltrexone injections
Status: Recruiting
Last Updated: 11 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The NYSPI site, which provides study oversight (no direct participant involvement) is currently paused and has been paused since an institutional pause on human subjects research began in June, 2023. The U.S. Department of Health and Human Services (HHS) Office of Human Research Protections (OHRP) issued an FWA restriction on NYSPI research that also included a pause of human subjects research as of June 23, 2023.

Detailed Description

This study will evaluate the effectiveness of a new pharmacological approach to increase efficacy of treatment with extended release naltrexone (XR-naltrexone) for individuals with opioid use disorder by combining it with buprenorphine-naloxone. Adding buprenorphine-naloxone after the patient initiated XR-naltrexone will not produce mu opioid agonist effect but kappa antagonist effects of buprenorphine may provide additional relief of protracted withdrawal, craving, and mood disturbances persisting in patients treated with XR-naltrexone and possibly contributing to premature treatment discontinuation and relapse. This is a parallel arm, double-blind, placebo-controlled study to examine whether addition of buprenorphine will improve treatment retention, reduce opioid craving, and improve mood over 24 weeks of treatment with XR-naltrexone administered every four weeks. Individuals with Opioid Use Disorder (OUD) and beginning treatment with XR-naltrexone for maintenance treatment will be randomized to treatment with adjunctive buprenorphine-naloxone or placebo with 5 additional doses of XR-naltrexone, given every four weeks, and weekly medication management. The study will provide detoxification and a first XR-Naltrexone injection if a participant consents before the first XR-naltrexone injection. In all participants randomization will occur after first XR-NTX injection. Buprenorphine-naloxone (sub-lingual (SL), 4/1 mg/day) or placebo will be started after a first XR-naltrexone dose and tapered off at study completion.

Registry

clinicaltrials.gov

Start Date

April 18, 2023

End Date

June 1, 2026

Last Updated

11 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

New York State Psychiatric Institute

Responsible Party

Principal Investigator

Adam Bisaga

Psychiatrist

New York State Psychiatric Institute

Eligibility Criteria

Inclusion Criteria

•Individuals between the ages of 18-65 (inclusive) interested in antagonist-based relapse prevention treatment
•Meets current DSM-5 criteria for current opioid use disorder of at least six months duration supported by urine toxicology positive for opioids OR Positive naloxone challenge (defined by 3-point increase in COWS) if seeking detoxification and XR-NTX induction OR confirmed recent detoxification treatment for opioids.
•In otherwise good health based on complete medical history, physical examination, vital signs measurement, ECG, and laboratory tests (hematology, blood chemistry, urinalysis) with no clinically significant abnormalities
•Participants who completed detoxification and received XR-NTX are eligible for the study. Participants may be enrolled up to 2 weeks following an initial XR-NTX injection given in any outside research or community-based treatment setting (inpatient, outpatient residential).
•Seeking treatment for opioid use disorder, willing to accept treatment with XR-NTX and, in the judgment of the treating physician, is a good candidate for naltrexone-based treatment.
•Voluntarily seeking treatment for opioid use disorder.
•Able to give written informed consent to participate in the study and showing a thorough understanding of the difference between agonist and antagonist-based treatment.

Exclusion Criteria

•Methadone maintenance within 2 weeks of XR-NTX induction or any use of methadone in the week prior to XR-NTX induction
•Maintenance on buprenorphine or frequent buprenorphine use in the week prior to XR-NTX induction (must be using no more than 8 mg of buprenorphine per day and no more than 3 days per week). If consenting after initial XR-NTX injection, any use of buprenorphine since XR-NTX induction is exclusionary.
•Serious medical, psychiatric or substance use disorder that, in the opinion of the study physician, would make a detoxification and naltrexone initiation, or maintenance treatment with XR-NTX in combination with buprenorphine, hazardous (relative contraindications) or requires a different level of care. Examples include:
•Disabling or terminal medical illness (e.g., uncompensated heart failure, severe acute hepatitis, cirrhosis or end-stage liver disease) as assessed by medical history and/or review of systems.
•Severe, untreated or inadequately treated mental disorder (e.g., active psychosis, uncontrolled manic-depressive illness) as assessed by history and/or clinical interview.
•Current severe alcohol, benzodiazepine, or other depressant or sedative hypnotic use likely to require a complicated medical detoxification (routine alcohol and sedative detoxifications may be included).
•Suicidal or homicidal
•AST/ALT \> 3x normal limit
•Pregnancy, lactation, or a plan of becoming pregnant. Women need to have negative blood pregnancy test at screening and agree to practice dual contraceptives.
•Physiological dependence on alcohol or sedative-hypnotics with impending withdrawal. Other substance use diagnoses are not exclusionary.