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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: Buprenorphine injection
* Drug: Naltrexone Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria 18-65 Years old OUD by DSM5 Criteria, confirmed by history and physical examination including urine toxicology, medical records and self-report Opioids are the drug of choice Interested in either injectable extended release agonist or antagonist treatment Have a stable address, working command of English language, and telephone access. Exclusion Criteria Lifetime diagnoses of any psychotic disorder, e.g. schizophrenia, schizoaffective disorder and bipolar affective disorder type 1. Psychiatric disorders requiring current medication treatment, e.g. moderate to severe depression, with the exception of mild to moderate Depressive and Anxiety disorders and Attention Deficit Hyperactivity Disorder that does not require prescription stimulants. Polysubstance users whose drug of choice is not an opioid. Medical contraindications for the study medications, e.g. active liver disease. Medical and surgical conditions such as malignancy that may affect patients' ability to receive XRNTX or XRBUP treatment because it may interfere with opioid analgesia. Contraindications for MRI, e.g. claustrophobia, indwelling foreign magnetic agents. Women of childbearing age who do not use an effective contraceptive.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Buprenorphine<br>Study participants receive three once-a-month injections of buprenorphine and complete weekly monitoring visits. | Drug: Buprenorphine injection<br>* Extended release once-a-month buprenorphine injection . Study arm undergoes 2 fMRI examinations and weekly monitoring visits<br>* Other names: Buprenorphine;|
| Active Comparator: Naltrexone<br>Study participants receive three once-a-month injections of naltrexone and complete weekly monitoring visits. | Drug: Naltrexone Injection<br>* Extended release once-a-month naltrexone injection. Study arm undergoes 2 fMRI examinations and weekly monitoring visits<br>* Other names: Naltrexone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fronto-limbic brain fMRI response to XRNTX and XRBUP |  | Phase 1 (Years 1-2) | 
| Fronto-limbic brain fMRI response to XRNTX and XRBUP |  | Phase 2 (Years 3-6) | 
| Urine Toxicology | Percentage of urine tests positive for opioids | Phase 1 (Years 1-2) | 
| Urine Toxicology | Percentage of urine tests positive for opioids | Phase 2 (Years 3-6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-reported continued opioid use | Report of illicit opioid use measured by Timeline Follow-Back Interview (TLFB) | Phase 1 (Years 1-2) | 
| Self-reported continued opioid use | Report of illicit opioid use measured by Timeline Follow-Back Interview (TLFB) | Phase 2 (Years 3-6) | 
| Adherence to treatment | The proportion of missed follow up visits out of the total available | Phase 1 (Years 1-2) | 
| Adherence to treatment | The proportion of missed follow up visits out of the total available | Phase 2 (Years 3-6) | 
| Opioid Craving | 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. | Phase 1 (Years 1-2) | 
| Opioid Craving | 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. | Phase 2 (Years 3-6) | 
| Self-reported Opioid Withdrawal | Measured by items using a Likert scale (0-4), Subjective Opioid Withdrawal Scale (SOWS), with higher ratings indicating more severe symptoms of opioid withdrawal | Phase 2 (Years 3-6) | 
| Clinician-reported Opioid Withdrawal | Measured by clinician-assessed values for Clinician Administered Opioid Withdrawal Scale (COWS) scale items. Higher values indicate more severe symptoms of opioid withdrawal. | Phase 2 (Years 3-6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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buprenorphine, naltrexone