# Efficacy of buprenorphine and XR-naltrexone combination for relapse prevention in opioid use disorder

> **NIH NIH U01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2020 · $1,258,359

## Abstract

Opioid use disorder (OUD) reached epidemic proportions in the US with more than 2.5 million individuals
affected and dramatic increase in unintentional opioid-related overdose deaths. While maintenance with
buprenorphine is a leading treatment for opioid-dependent individuals, this is not acceptable to some patients,
nor is it universally effective as approximately 50% of individuals treated with buprenorphine continue using
illicit opioids and/or drop out during the first 6 months of treatment. Naltrexone, a mu-opioid receptor
antagonist, given as extended-release (XR) preparation, offers an alternative approach for patients who have
failed prior agonist trials or those who are not suitable or agreeable to agonist maintenance. Naltrexone is
fitting for individuals seeking recovery without opioid agonists as it offers the promise of securing abstinence
and circumventing the high relapse rates currently observed following opioid detoxification. However, at
present time only 50% of patients are successfully retained in treatment with XR-naltrexone over long period of
time which limits it protective effects and can be a barrier to a widespread dissemination and acceptance of
antagonist-based treatment. In the proposed trial, we will test the effectiveness of a new pharmacological
approach to increase the proportion of patients successfully retained on XR-naltrexone by combining it with
buprenorphine administered daily. Adding buprenorphine after the patient received XR-naltrexone will not
produce mu opioid agonist effect but remaining 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.
The goal of this five-year study is to test whether addition of buprenorphine will improve treatment retention,
reduce opioid craving, and improve mood over the subsequent 6-months of treatment during which participants
will receive six XR-naltrexone injections and relapse-prevention therapy. We will conduct a placebo-controlled,
double-blind, two parallel arm clinical trial with 1:1 randomization to evaluate the safety and the efficacy of
buprenorphine 4 mg/d administered concurrently with XR-naltrexone. Individuals with OUD seeking treatment
with naltrexone will be detoxified and after they receive XR-naltrexone they will be randomized to treatment
with buprenorphine (N = 60), or placebo (N = 60) with 5 additional doses of XR-naltrexone, given every 4
weeks, and weekly therapy. Buprenorphine (4 mg/d) or placebo will be started after the first XR-naltrexone
dose and tapered off after the final XR-naltrexone injection. The primary outcome measure will be the
proportion of patients successfully retained to receive six consecutive XR-naltrexone injection. Severity of
withdrawal symptoms craving, sleep disturbance, and opioid use will be also measured. If found effectiv...

## Key facts

- **NIH application ID:** 9738472
- **Project number:** 1U01DA046430-01A1
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** ADAM BISAGA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,258,359
- **Award type:** 1
- **Project period:** 2020-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9738472

## Citation

> US National Institutes of Health, RePORTER application 9738472, Efficacy of buprenorphine and XR-naltrexone combination for relapse prevention in opioid use disorder (1U01DA046430-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9738472. Licensed CC0.

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