The Effect of Chronic Pain on Delay Discounting in Methadone Patients

NCT ID: NCT04473950

Last Updated: 2025-03-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-08
• Study Completion Date: 2022-10-06

Brief Summary

The epidemic of opioid overdose deaths continues to rise, killing more persons in 2017 than HIV/AIDS at the height of that epidemic. Medication assisted treatment, including methadone and buprenorphine, is the standard of care for the treatment of opioid use disorder (OUD). However, chronic pain can reduce treatment efficacy during medication assisted treatment and is associated with illicit substance relapse, dropout, and subsequent overdose. Mechanisms by which chronic pain may influence the impulsive decision making (e.g., drug relapse) in persons with OUD have not been well characterized. A better understanding is needed of decision-making in this population. Two factors that can influence decisions to use drugs are impulsivity and acute opioid withdrawal. This proposal will test how chronic pain is associated with increases in impulsive decision making in OUD, whether impulsive decision making is greater when undergoing opioid withdrawal, and how catastrophizing may modify the association between withdrawal and impulsive decision making in patients with chronic pain and OUD. An ideal population for this developmental research project are methadone maintained patients, who show high treatment attendance rates and will therefore assure study efficiency and reliable completion.

Detailed Description

This is an outpatient Phase 1 clinical trial investigating the effect of naloxone precipitated withdrawal on delay discounting. Eligible participants will undergo two experimental sessions presented in random order. One session will involve the measurement of delay discounting 30 minutes after double-blind intramuscular (IM) administration of placebo (normal saline) and the other will have the exact same procedures performed after double-blind IM administration of naloxone (0.1 mg). Injections will occur 2 hours after methadone dosing (peak levels). Study sessions will last 2 hours and involve pain and opioid withdrawal measures assessed at baseline and 15 minute intervals after injections. The participant should be back to baseline and free of withdrawal by the end of the study session. Sessions will occur at least 48 hours apart.

Conditions

Opioid-use Disorder; Chronic Pain Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Pain Group

Patients with chronic pain who are maintained on methadone for opioid use disorder

Group Type: EXPERIMENTAL

Naloxone Hydrochloride

Intervention Type: DRUG

An intramuscular (IM) injection of naloxone will be given.

Placebo

Intervention Type: DRUG

An IM injection of 0.9% normal saline will be given.

No Pain Group

Patients who are maintained on methadone for opioid use disorder but who do not have chronic pain.

Group Type: PLACEBO_COMPARATOR

Naloxone Hydrochloride

Intervention Type: DRUG

An intramuscular (IM) injection of naloxone will be given.

Placebo

Intervention Type: DRUG

An IM injection of 0.9% normal saline will be given.

Interventions

Naloxone Hydrochloride

An intramuscular (IM) injection of naloxone will be given.

Intervention Type: DRUG

Placebo

An IM injection of 0.9% normal saline will be given.

Intervention Type: DRUG

Other Intervention Names

Narcan

Eligibility Criteria

Inclusion Criteria

• Male and female adults aged 18-65
• Stable methadone dose (at least 21 days) verified by contacting participant's opioid treatment program
• Understand and speak English
• Urine toxicology screen negative for drugs of abuse and positive for methadone
• Participants must be without signs of intoxication as evidenced by ability to receive full dose of methadone prior to research activities.
• Presence of chronic pain (>3 months) for the Pain group and absence of pain for the No Pain group.

Exclusion Criteria

• Unstable psychiatric illness as assessed by the Mini International Neuropsychiatric Interview (e.g. active suicidal ideation, psychosis)
• Unstable medical illness as assessed by the study's independent medical monitor (e.g. uncontrolled hypertension, recent myocardial infarction, recent stroke, unstable angina) that may be affected by precipitated withdrawal
• Prescription opioid use besides methadone
• Acute pain process unrelated to chronic pain
• Women who are pregnant or lactating
• Known allergy to naloxone

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

D. Andrew Tompkins, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

Zuckerberg San Francisco General Hospital

San Francisco, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R21DA047520

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Z-1902

Identifier Type: -

Identifier Source: org_study_id