The Effect of Chronic Pain on Delay Discounting in Methadone Patients

March 11, 2025 updated by: University of California, San Francisco
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94110
        • Zuckerberg San Francisco General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pain Group
Patients with chronic pain who are maintained on methadone for opioid use disorder
Drug: Naloxone Hydrochloride
An intramuscular (IM) injection of naloxone will be given.
Other Names:
  • Narcan
Drug: Placebo
An IM injection of 0.9% normal saline will be given.
Placebo Comparator: No Pain Group
Patients who are maintained on methadone for opioid use disorder but who do not have chronic pain.
Drug: Naloxone Hydrochloride
An intramuscular (IM) injection of naloxone will be given.
Other Names:
  • Narcan
Drug: Placebo
An IM injection of 0.9% normal saline will be given.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Delay Discounting of Money Rate (k)
Time Frame: 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.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Study Session Peak Pain Visual Analog Scale (VAS)
Time Frame: Peak Pain VAS will be the highest rating during each 2 hour study session.
Current pain level rated on 0-100 VAS. This is the validated pain scale typically used by clinicians in an outpatient or inpatient clinical visit to represent current level of pain. Higher ratings indicate worse pain severity.
Peak Pain VAS will be the highest rating during each 2 hour study session.
Peak Clinical Opiate Withdrawal Scale (COWS) Rating
Time Frame: Peak COWS rating will be the highest rating during each 2 hour study session.
The COWS is an 11-item validated clinician administered scale that quantifies level of opioid withdrawal. The range of scores is 0-48, with higher scores indicating greater withdrawal severity. The peak COWS rating will be the highest measurement in the session after study drug administration.
Peak COWS rating will be the highest rating during each 2 hour study session.
Peak Subjective Opiate Withdrawal Scale (SOWS) Rating
Time Frame: Peak SOWS rating will be the highest rating during each 2 hour study session.
The SOWS is a 16 item validated self-administered scale for grading opioid withdrawal symptoms. The range of scores is 0-64, with higher scores indicating greater withdrawal severity. The peak SOWS rating will be the highest measurement in the session after study drug administration.
Peak SOWS rating will be the highest rating during each 2 hour study session.
Peak Increase From Baseline Pupil Diameter
Time Frame: Peak increase from baseline pupil diameter will be the largest increase from baseline pupil diameter measured during each 2 hour study session.
Pupil diameter (mm) will be measured via digital pupillometer in standard room lighting at baseline and then throughout the study session after study drug administration. The peak increase from baseline value will be the largest increase from baseline pupil diameter measured after study drug administration.
Peak increase from baseline pupil diameter will be the largest increase from baseline pupil diameter measured during each 2 hour study session.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, San Francisco

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)
Johns Hopkins University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: D. Andrew Tompkins, MD, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 8, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 6, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 6, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 12, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 13, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 16, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 26, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Z-1902
  • R21DA047520 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be made available to the public through presentation at scientific meetings and research publications in peer-reviewed journals. I have routinely kept an open policy to share data with the scientific and medical community upon request, and this policy will be continued with the present project.

IPD Sharing Time Frame

Data will become available after publication of the main study results.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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