Neurobehavioral Mechanisms of Choice in Opioid Use Disorder

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.

Study Overview

• Status: Recruiting
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Drug: Oxycodone; Drug: Remifentanil

• Study Type: Interventional
• Enrollment (Estimated): 31
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Joshua Lile, Ph.D.; Phone Number: 8593236034; Email: jalile2@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0086
      • Recruiting
      • Laboratory of Human Behavioral Pharmacology
      • Contact: Frances Wagner, RN; Phone Number: 859-257-5388; Email: fpwagn2@uky.edu
      • Principal Investigator: Joshua A. Lile, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active treatment followed by placebo treatment; 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; Participants receive oxycodone or placebo.; Drug: Remifentanil; Participants with a history of IV opioid use can opt to complete a session in which they receive remifentanil.
Experimental: Placebo treatment followed by active treatment; 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; Participants receive oxycodone or placebo.; Drug: Remifentanil; Participants with a history of IV opioid use can opt to complete a session in which they receive remifentanil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiration rate	Breaths per minute measured by capnography device	Measured continuously during a single 2.5 hour session in which remifentanil is administered.
End tidal carbon dioxide	End tidal carbon dioxide measured by capnography device	Measured continuously during a single 2.5 hour session in which remifentanil is administered.
Oxygen saturation	Blood oxygen concentration measured by capnography device	Measured continuously during a single 2.5 hour session in which remifentanil is administered.

Collaborators and Investigators

• Sponsor: Joshua A. Lile, Ph.D.
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: JOSHUA LILE, Ph.D., University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2019
• Primary Completion (Estimated): March 30, 2025
• Study Completion (Estimated): March 30, 2025

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 18, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): January 12, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil; Oxycodone
• Other Study ID Numbers: 47844; R01DA047368 (U.S. NIH Grant/Contract)

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