Cognitive Function and Pain Threshold in People Who Are Methadone Maintained (OUD)

Effects of Methadone on Cognitive Function and Pain Threshold

Male and female participants, over the age of 18, with OUD currently receiving methadone will be enrolled. This within-subject study design will assess pain and cognitive performance in individuals with OUD engaged in MMT. Participants will be asked to complete two separate 4-hour sessions that will be spaced approximately 2-15 days apart. The two sessions will differ based on methadone administration to evaluate study variables in methadone peak (immediately after dose) and trough (20-24 hour after last dose) states. The order of these sessions will be counterbalanced across participants. At the beginning of each session, participants will complete a pain sensitivity task at baseline and post-methadone administration to determine pain threshold and tolerance. Participants will then complete computerized cognitive assessments of working memory, set-shifting, attentional bias, and behavioral inhibition. The cognitive assessments will administered across three time-points (0, 90, and 180 minutes). Pain threshold and tolerance will be measured again after 240 minutes. In addition, opioid craving, withdrawal, pain intensity, and emotional valence will be repeatedly assessed during 240 minute session.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Methadone; Drug: Methadone

Detailed Description

After completion of the phone screen, eligible participants will be brought into the laboratory, given a description of the study, and assessed on inclusion and exclusion criteria by research personnel. Details pertaining to the cognitive measures, pain measures, and methadone manipulation will be discussed and informed consent will be obtained along with a signed release to allow study personnel to monitor opioid maintenance. Information on medical, psychiatric and drug use histories will be collected. Individuals with a history of vascular problems or high blood pressure will be evaluated by the research physician. In addition, laboratory tests collecting information on blood alcohol content and urine toxicology will be conducted. Participants will be deemed ineligible to participate if they are not medically cleared by research clinician. Veterans who have a positive BAC will be rescheduled and the methadone maintenance program's clinical protocol will be implemented.

All sessions will be conducted at the West Haven VA Connecticut Healthcare Campus. Participants will be asked to complete two sessions, approximately 2-15 days apart. Order of peak and trough sessions will be counterbalanced between participants. Each session will last approximately four hours. Prior to each testing session, participants will be asked to refrain from caffeine for at least one hour. They will be served a standardized breakfast (i.e., bagel and cream cheese) and offered one smoke break prior to beginning the experimental session. They will be asked to refrain from smoking until the completion of the study protocol. Methadone administration will be coordinated with methadone maintenance treatment staff to relay information about which condition the participant will complete on a given session. At the start of each session, participants will complete computerized cognitive assessments and self-report questionnaires. The computerized cognitive measures will repeated at hours 0, 1.5, and 3. Several state questionnaires will be administered at hours every 30 minutes. Participants will also complete a pain sensitivity measure (i.e., cold pressor task) to assess baseline threshold and tolerance at hour 0 and hour 4.

This study is complete with 27 enrolled and 20 completers.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Veteran Affairs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females, over the age of 18
• Diagnosed with opioid dependence and currently enrolled in methadone maintenance treatment
• Compliant in opioid maintenance treatment and on a stable dose for two weeks or greater
• No current medical problems deemed contraindicated for participation by physician investigator

Exclusion Criteria:

• History of psychosis as determined by review of EMR.
• Acute suicidal ideation.
• History of medical conditions that the physician investigator deems contraindicated for inclusion in the study (e.g., untreated hypertension)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: administration immediate; Methadone will be administered prior to study procedures	Drug: Methadone; Methadone will be administered before study procedures; Drug: Methadone; Methadone will be delayed (4 hours) until the end of the procedures
Experimental: administration delayed; Methadone will be held for four hours until the end of all study procedures.	Drug: Methadone; Methadone will be administered before study procedures; Drug: Methadone; Methadone will be delayed (4 hours) until the end of the procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in cognitive functioning using the go no go task	during methadone peak and trough states.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
self-reported measures of pain from the cold pressor test	during methadone peak and trough states	up to 24 months

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D., Veteran Affairs Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): March 10, 2021
• Study Completion (Actual): April 28, 2021

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Actual): July 20, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Methadone
• Other Study ID Numbers: MS057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will be de-identified and will only be used with this Principle Investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No