RecruitingPhase 2Phase 3NCT05011266

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

Sponsor

New York State Psychiatric Institute

Enrollment

180 participants

Start Date

Apr 18, 2023

Study Type

INTERVENTIONAL

Conditions

Opioid-use Disorder

Summary

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. This is a two arm, double-blind, placebo-controlled study to examine whether addition of buprenorphine-naloxone will improve treatment retention, reduce opioid craving, and improve mood over 24 weeks of treatment with extended release naltrexone (XR-naltrexone) administered every four weeks for a total of 6 injections. 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.

Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria7

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 Criteria15

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 for 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.
History of allergic or adverse reaction to buprenorphine, naltrexone, naloxone, clonidine, or clonazepam.
Painful medical condition that requires ongoing opioid analgesia or anticipated surgery necessitating opioid medications.
Individuals above 60 with possible early cognitive decline or other neurodegenerative conditions as evidenced by a score of less than 25 on a Mini Mental Status Exam screen.
Participants who had 30 or more opioid-free days prior to randomization will not be eligible.
Participants more than 2 weeks following an initial XR-NTX injection (given in any outside research or community-based treatment setting, for example inpatient, outpatient residential).