Brain Mechanisms of Pharmacotherapy in Opioid Use Disorder

Brain Mechanisms of Cognitive Response to Pharmacotherapy in Opioid Use Disorder

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.

Study Overview

• Status: Terminated
• Conditions: Opioid Dependence
• Intervention / Treatment: Drug: Brixadi; Drug: Vivitrol

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 Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • 3535 Market Street, Suite 4100, University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Buprenorphine; Participants assigned to treatment with extended-release buprenorphine	Drug: Brixadi; Extended release injectable Buprenorphine; Other Names: Buprenorphine Injectable Product
Active Comparator: Naltrexone; Participants assigned to treatment with extended-release naltrexone	Drug: Vivitrol; Extended release injectable Naltrexone; Other Names: Naltrexone Injectable Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI Signal	Brain fMRI response to neurocognitive probes	up to 90 days
Urine Toxicology: Opioid	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	Through the study completion, up to 120 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety	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.	Through the study completion, up to 120 days
Depression	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.	Through the study completion, up to 120 days
Non-opioid Urine Toxicology	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*	Through the study completion, up to 120 days

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: James Loughead, Ph.D., University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Actual): August 31, 2024
• Study Completion (Actual): August 31, 2024

Study Registration Dates

• First Submitted: June 18, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: buprenorphine; neuroimaging; naltrexone
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Alcohol Deterrents; Narcotic Antagonists; Buprenorphine; Naltrexone
• Other Study ID Numbers: 843403

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No