Neurobehavioral Mechanisms of Choice in Opioid Use Disorder

NCT03958474 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: 47844R01DA047368
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this protocol is to use probabilistic reinforcement learning choice tasks and magnetic resonance neuroimaging to demonstrate the impact of problematic opioid use and opioid withdrawal on dynamic decision-making and reveal the neurobehavioral and neurobiological processes underlying abnormal task performance. A second objective is to identify an appropriate dose of intravenous remifentanil for subsequent studies in physically dependent individuals with opioid use disorder.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (1)

• Gambling task

  The number of monetary rewards earned on a gambling task, in which two options signaled by distinct cues are presented on a computer screen and choosing either could result in the delivery of money, but the reinforcement probabilities of the options differ, and change during the task.

  Change in monetary rewards earned on a gambling task as a function of the intervention will be assessed by administering this task once per session across two sessions during a 9-day inpatient enrollment in each subject

Study Arms (2)

Active treatment followed by placebo treatment

EXPERIMENTAL

Participants complete a gambling task during oxycodone administration and then complete the same gambling task during placebo administration. Participants with a history of IV opioid use can opt to complete a final remifentanil dose-ranging session.

Drug: Oxycodone; Drug: Remifentanil

Placebo treatment followed by active treatment

EXPERIMENTAL

Participants complete a gambling task during placebo administration and then complete the same gambling task during oxycodone administration. Participants with a history of IV opioid use can opt to complete a final remifentanil dose-ranging session.

Drug: Oxycodone; Drug: Remifentanil

Interventions

Oxycodone DRUG

Participants receive oxycodone or placebo.

Active treatment followed by placebo treatment; Placebo treatment followed by active treatment

Remifentanil DRUG

Participants with a history of IV opioid use can opt to complete a session in which they receive remifentanil.

Active treatment followed by placebo treatment; Placebo treatment followed by active treatment

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Must meet moderate/severe criteria for moderate/severe opioid use disorder, report recent prescription or illicit opioid use, and be opioid dependent, as evidenced by either a urine sample positive for recent opioid use or being in frank withdrawal during screening.
• Female subjects must be using an effective form of birth control (e.g., birth control pills, surgical sterilization, IUD, cervical cap with a spermicide, or abstinence).
• Able to speak and read English
• Subjects who are interested in completing the remifentanil dose-ranging session must report a history of intravenous opioid use and a baseline O2 saturation of 95% or greater.

You may not qualify if:

• History of, or current, clinically significant physical disease (e.g., respiratory disease \[asthma, COPD, sleep apnea\], impaired cardiovascular functioning, seizure disorder or CNS tumors) or current or past history of psychiatric disorder that would limit compliance in the studies, other than substance use disorder.
• Meet diagnostic criteria for psychoactive substance use disorder for substances other than opioids (OUD subjects only) or nicotine that would require detoxification (i.e., alcohol, benzodiazepines or barbiturates).
• Contraindications for MRI scanning (e.g., pacemaker, metal implants, claustrophobia, or any other implanted medical device).
• Vision or hearing problems that would preclude completion of experimental tasks.
• At risk for respiratory complications and have predictors of difficult bag mask ventilation (e.g., dentures, very full beard), in case emergency respiratory intervention is needed.
• Seeking treatment for SUD.
• Poor venous access (only subjects who will participate in the remifentanil dose-ranging session).

Sponsors & Collaborators

• Joshua A. Lile, Ph.D.: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Laboratory of Human Behavioral Pharmacology

Lexington, Kentucky, 40536-0086, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Oxycodone; Remifentanil

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• JOSHUA LILE, Ph.D.

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Within-subjects design

Study Record Dates

• First Submitted: May 16, 2019
• First Posted: May 22, 2019
• Study Start: August 16, 2019
• Primary Completion: July 10, 2025
• Study Completion: July 10, 2025
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)