Brain Mechanisms of Pharmacotherapy in Opioid Use Disorder

Opioid Dependence Clinical Trial

Official title:

Brain Mechanisms of Cognitive Response to Pharmacotherapy in Opioid Use Disorder

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04454411
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: February 1, 2025
• Est. completion date: January 1, 2027

Study information

• Verified date: October 2023
• Source: University of Pennsylvania
• Contact: Daniel Langleben, M.D.
• Phone: 215-746-0107
• Email: langlebe[@]pennmedicine.upenn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: January 1, 2027
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Opioid Dependence
• Opioid-Related Disorders

Intervention

Drug:
• Brixadi
Extended release injectable Buprenorphine
• Vivitrol
Extended release injectable Naltrexone

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional Magnetic Resonance Imaging (fMRI) signal	Brain fMRI response to neurocognitive probes	up to 90 days
Primary	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	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
Secondary	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
Secondary	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