Brain Mechanisms of Pharmacotherapy in Opioid Use Disorder

University of Pennsylvania

Status and phase: Terminated; Phase 2

Conditions: Opioid Dependence

Treatments: Drug: Vivitrol; Drug: Brixadi

Study type: Interventional

Funder types: Other

Identifiers

NCT04454411

843403

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3 participants in 2 patient groups

Buprenorphine

Experimental group

Description:

Participants assigned to treatment with extended-release buprenorphine

Treatment:

Drug: Brixadi

Naltrexone

Active Comparator group

Description:

Participants assigned to treatment with extended-release naltrexone

Treatment:

Drug: Vivitrol