Clinical trial NCT05596955: Open Label Comparison of Injectable Buprenorphine ( Brixadi®) and Naltrexone (Vivitrol®) for Opioid Use Disorder
Official title: Open Label Comparison of Injectable Buprenorphine ( Brixadi®) and Naltrexone (Vivitrol®) for Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Opioid Use Disorder
Keywords: buprenorphine
naltrexone
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2022-10-27
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria

1. 18-65 Years old
2. OUD by DSM5 Criteria, confirmed by history and physical examination including urine toxicology, medical records and self-report
3. Opioids are the drug of choice
4. Interested in either injectable extended release agonist or antagonist treatment
5. Have a stable address, working command of English language, and telephone access.

Exclusion Criteria

1. Lifetime diagnoses of any psychotic disorder, e.g. schizophrenia, schizoaffective disorder and bipolar affective disorder type 1.
2. 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.
3. Polysubstance users whose drug of choice is not an opioid.
4. Medical contraindications for the study medications, e.g. active liver disease.
5. 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.
6. Contraindications for MRI, e.g. claustrophobia, indwelling foreign magnetic agents.
7. Women of childbearing age who do not use an effective contraceptive.

Primary outcomes:
measure: Fronto-limbic brain fMRI response to XRNTX and XRBUP
timeFrame: Phase 1 (Years 1-2)
measure: Fronto-limbic brain fMRI response to XRNTX and XRBUP
timeFrame: Phase 2 (Years 3-6)
measure: Urine Toxicology
timeFrame: Phase 1 (Years 1-2)
measure: Urine Toxicology
timeFrame: Phase 2 (Years 3-6)
Secondary outcomes:
measure: Self-reported continued opioid use
timeFrame: Phase 1 (Years 1-2)
measure: Self-reported continued opioid use
timeFrame: Phase 2 (Years 3-6)
measure: Adherence to treatment
timeFrame: Phase 1 (Years 1-2)
measure: Adherence to treatment
timeFrame: Phase 2 (Years 3-6)
measure: Opioid Craving
timeFrame: Phase 1 (Years 1-2)
measure: Opioid Craving
timeFrame: Phase 2 (Years 3-6)
measure: Self-reported Opioid Withdrawal
timeFrame: Phase 2 (Years 3-6)
measure: Clinician-reported Opioid Withdrawal
timeFrame: Phase 2 (Years 3-6)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Addiction Treatment Center, University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania, Psychiatry
name: James Loughead, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: