The Effect of Chronic Pain on Delay Discounting in Methadone Patients

NCT04473950 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: Z-1902R21DA047520
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid-use Disorder; Chronic Pain Syndrome

Keywords

delay discounting; pain catastrophizing; impulsivity

Outcome Measures

Primary Outcomes (1)

• Delay Discounting of Money Rate (k)

  Delay discounting is the relative preference for smaller sooner over larger later rewards, an aspect of impulsivity. Most individuals would prefer an immediate $100 over $100 delayed by 1 year. However, when faced with the choice between receiving $95 now versus $100 in 1 year, preferences for the delayed reward may increase. By assessing such choices across multiple delays, delay discounting quantifies the devaluation of rewards over time, which allows for an index of overall discounting rate (k). Delay Discounting of money rate has no units and values can go from 0-infinity. A larger discount rate indicates that a future reward is devalued more, and is associated with more impulsive behavior.

  k will be calculated from the same series of discounting questions that will be asked once each session at approximately 30 minutes after study medication administration.

Secondary Outcomes (4)

• Study Session Peak Pain Visual Analog Scale (VAS)

  Peak Pain VAS will be the highest rating during each 2 hour study session.

• Peak Clinical Opiate Withdrawal Scale (COWS) Rating

  Peak COWS rating will be the highest rating during each 2 hour study session.

• Peak Subjective Opiate Withdrawal Scale (SOWS) Rating

  Peak SOWS rating will be the highest rating during each 2 hour study session.

• Peak Increase From Baseline Pupil Diameter

  Peak increase from baseline pupil diameter will be the largest increase from baseline pupil diameter measured during each 2 hour study session.

Study Arms (2)

Pain Group

EXPERIMENTAL

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

Drug: Naloxone Hydrochloride; Drug: Placebo

No Pain Group

PLACEBO COMPARATOR

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

Drug: Naloxone Hydrochloride; Drug: Placebo

Interventions

Naloxone Hydrochloride DRUG

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

Also known as: Narcan

No Pain Group; Pain Group

Placebo DRUG

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

No Pain Group; Pain Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Johns Hopkins University: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Impulsive Behavior

Interventions

Naloxone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

COVID-19 Public Health Emergency caused almost complete stoppage of research activities for over half of the grant time. We only had 10% of the proposed number of completers. Therefore, the decision was made to halt the study.

Results Point of Contact

• Title: David Andrew Tompkins, MD, MHS
• Organization: University of California, San Francisco

david.tompkins@ucsf.edu

628-206-3645

Study Officials

• D. Andrew Tompkins, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participant, investigator, medical personnel administering study drug, and outcomes assessor will be blinded to drug being administered.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This proposal is a randomized double-blind placebo controlled Phase 1 clinical trial / human laboratory study

Study Record Dates

• First Submitted: June 12, 2020
• First Posted: July 16, 2020
• Study Start: January 8, 2020
• Primary Completion: October 6, 2022
• Study Completion: October 6, 2022
• Last Updated: March 26, 2025
• Results First Posted: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will become available after publication of the main study results.

Locations

US (1)