Brain Mechanisms of Pharmacotherapy in Opioid Use Disorder

Phase 2

Not yet recruiting

• Conditions: Opioid Dependence
• Interventions: Drug: Vivitrol; Drug: Brixadi

• Registration Number: NCT04454411
• Lead Sponsor: University of Pennsylvania

Brief Summary

This study will investigate the mechanisms of cognitive-behavioral response to medications used for relapse prevention in opioid use disorder (opioid addiction, OUD), through investigation of the neural circuits underlying key cognition functions. The study will use previously validated cognitive probes, functional Magnetic Resonance Imaging (fMRI), and novel extended-release injectable preparations of opioid partial agonist buprenorphine and antagonist naltrexone, in OUD patients to explain the individual heterogeneity of OUD treatment response.

Detailed Description

This proposal seeks to identify the neural circuits underlying the cognitive effects of medication assisted therapy (MAT) for OUD. The study will examine the neurocognitive effects of MAT by comparing two preparations with different pharmacodynamic properties (extended release buprenorphine and naltrexone, XRBUP, XRNTX) in three key domains (incentive salience, executive functioning, and emotion processing) using task functional Magnetic Resonance Imaging (MRI). In the 1st phase of the study, forty treatment-seeking OUD patients will be randomized to XRNTX or XRBUP groups after detoxification. Participants will undergo medication induction followed by monthly injections and urine toxicology monitoring for 120 days. Neuroimaging will follow completion of detoxification (pre-treatment) and 15 days after the second injection (on-treatment). The second study phase will extend the paradigm to an independent sample of 160 additional participants and test the explanatory value of MAT-induced changes in the neuroimaging signal in the classification of OUD treatment outcomes.

Study Timeline

• Study First Submitted: 2020-06-18
• Study First Submitted QC: 2020-06-26
• Study First Posted: 2020-07-01
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-29
• Last Update Posted: 2024-11-01
• Study Start: 2025-02-01
• Primary Completion: 2026-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

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

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Exclusion Criteria

1. Psychiatric Co-morbidities:

   1. Lifetime diagnoses of any psychotic disorder, e.g. schizophrenia, schizoaffective disorder, bipolar disorder type 1.
   2. Psychiatric Co-morbidities: Psychiatric disorders requiring current medication treatment, e.g. moderate to severe depression. Mild to moderate Depressive and Anxiety disorders and Attention Deficit Hyperactivity Disorder that do not require prescription stimulants and DSM5 Cluster B and C personality disorders are also allowed.
   3. Polysubstance users whose drug of choice is not opioids.

2. Contraindications for XRNTX or XRBUP e.g. active liver disease.

3. 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

4. Contraindications for MRI, e.g. claustrophobia, indwelling foreign magnetic agents.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Naltrexone	Vivitrol	Participants assigned to treatment with extended-release naltrexone
Buprenorphine	Brixadi	Participants assigned to treatment with extended-release buprenorphine

Primary Outcome Measures

Name	Time	Method
Urine Toxicology: opioid	Through the study completion, up to 120 days	Rapid semi-quantitative ELISA urine drug screen test for morphine, oxycodone and methadone, followed by (cut off levels): Methadone (MTD) Methadone 300 ng/mL Opiates (OPI 300) Morphine Morphine \*\*300 ng/mL Oxycodone (OXY) Oxycodone 100 ng/mL
Functional Magnetic Resonance Imaging (fMRI) signal	up to 90 days	Brain fMRI response to neurocognitive probes

Secondary Outcome Measures

Name	Time	Method
Anxiety	Through the study completion, up to 120 days	Hamilton Anxiety Rating Scale (HAM-A) (Hamilton, 1967). The HAM-A is a 15-minute, 14-item, clinician-administered instrument that measures current anxiety and changes in anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Depression	Through the study completion, up to 120 days	Hamilton Depression Rating Scale (HAM-D) (Hamilton, 1959 #2497). The HAM-D is a 20-minute, 24-item interview that measures the severity of depression and changes in depressive symptoms. HAM-D form includes 21 items, however the scoring is based on the first 17. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. The HAM-D score level corresponds to the clinical severity of depression as follows: 10 - 13 mild; 14-17 mild to moderate; \>17 moderate to severe.
Non-opioid Urine Toxicology	Through the study completion, up to 120 days	Rapid semi-quantitative ELISA urine drug screen test for amphetamine/methamphetamine, benzodiazepines, cocaine, phencyclidine, cannabinoids and cotinine, with cut off levels: Amphetamine/Methamphetamine 500/1000ng/ml Benzodiazepines Enzyme Immunoassay (EIA) 200 ng/mL Cocaine Metabolite (Benzoylecgonine) EIA 150/300 ng/mL Cotinine EIA 250 ng/mL Phencyclidine EIA 25 ng/mL THC (Cannabinoids) EIA 20/50 ng/mL\*