Open Label Comparison of Injectable Buprenorphine ( Brixadi®) and Naltrexone (Vivitrol®) for Opioid Use Disorder

Phase 2

Terminated

• Conditions: Opioid Use Disorder
• Interventions: Drug: Buprenorphine injection; Drug: Naltrexone Injection

• Registration Number: NCT05596955
• Lead Sponsor: University of Pennsylvania

Brief Summary

This project aims to elucidate the brain effects of opioid use disorder (OUD) treatments. The study will investigate the cognitive effects of extended-release preparations of a partial opioid agonist and an antagonist. To this end, the study will use up to three monthly injections of buprenorphine (XRBUP, Brixadi®) and naltrexone (XRNTX, Vivitrol®). Domain-specific brain activity will be induced by cognitive tasks and recorded with Magnetic Resonance Imaging. Participants will be imaged at baseline and in the interval between the 1st and 2nd injection and followed for up to three months.

Detailed Description

This study will elucidate the cognitive mechanisms of response to opioid agonists and antagonists used to prevent relapse in OUD through investigation of the underlying neural circuits. The study will use previously validated cognitive probes, functional Magnetic Resonance Imaging (fMRI), and extended-release injectable preparations of opioid partial agonist buprenorphine (XRBUP, Brixadi) and opioid antagonist naltrexone (XRNTX, Vivitrol), in OUD patients. Using two medications with opposing mu opioid receptor action, the study will allow a comprehensive evaluation of the mechanisms of response to relapse prevention pharmacotherapy in OUD. The study will determine the presence of treatment effects in the domains of executive function, incentive salience, and resting functional connectivity and the interaction that will indicate a difference between the two medications. The study will evaluate the ability of the brain fMRI signal to explain relapse defined by % of opioid-positive urine tests and adherence to the study interventions. The study will screen recently detoxified treatment-seeking participants with OUD who will receive 2 monthly injections of XR-NTX or XR-BUP and have weekly urine toxicology monitoring. The project will enroll 200 participants over 6 years. The proposal would be the first neural systems' level investigation of the cognitive effects of the next generation extended release preparation of buprenorphine and naltrexone to explain the individual heterogeneity of OUD treatment response and failure. This project has the potential to advance the theory and personalized treatment of OUD by elucidating the brain mechanisms of vulnerability to relapse in OUD and in SUD in general.

Study Timeline

• Study First Submitted: 2022-04-05
• Study Start: 2022-08-01
• Study First Submitted QC: 2022-10-24
• Study First Posted: 2022-10-27
• Primary Completion: 2024-08-31
• Study Completion: 2024-08-31
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-14
• Last Update Posted: 2025-03-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Buprenorphine	Buprenorphine injection	Study participants receive three once-a-month injections of buprenorphine and complete weekly monitoring visits.
Naltrexone	Naltrexone Injection	Study participants receive three once-a-month injections of naltrexone and complete weekly monitoring visits.

Primary Outcome Measures

Name	Time	Method
Fronto-limbic brain fMRI response to XRNTX and XRBUP	Phase 2 (Years 3-6)
Urine Toxicology	Phase 2 (Years 3-6)	Percentage of urine tests positive for opioids

Secondary Outcome Measures

Name	Time	Method
Opioid Craving	Phase 2 (Years 3-6)	Self-reported craving for opioids measured standard clinical questionnaire (OCS) to determine opioid craving severity (0-10). Higher rating on items indicate more severe craving symptoms and increased likelihood of near term use.
Adherence to treatment	Phase 2 (Years 3-6)	The proportion of missed follow up visits out of the total available
Self-reported Opioid Withdrawal	Phase 2 (Years 3-6)	Measured by items using a Likert scale (0-4), Subjective Opioid Withdrawal Scale (SOWS), with higher ratings indicating more severe symptoms of opioid withdrawal
Clinician-reported Opioid Withdrawal	Phase 2 (Years 3-6)	Measured by clinician-assessed values for Clinician Administered Opioid Withdrawal Scale (COWS) scale items. Higher values indicate more severe symptoms of opioid withdrawal.
Self-reported continued opioid use	Phase 2 (Years 3-6)	Report of illicit opioid use measured by Timeline Follow-Back Interview (TLFB)

Trial Locations

Locations (1)

Addiction Treatment Center, University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States