Clinical trial NCT04473950: The Effect of Chronic Pain on Delay Discounting in Methadone Patients
Official title: The Effect of Chronic Pain on Delay Discounting in Methadone Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Opioid-use Disorder
Chronic Pain Syndrome
Keywords: delay discounting
pain catastrophizing
impulsivity
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
name: National Institute on Drug Abuse (NIDA)
First posted: 2020-07-16
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This proposal is a randomized double-blind placebo controlled Phase 1 clinical trial / human laboratory study
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Delay Discounting of Money Rate (k)
timeFrame: 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:
measure: Study Session Peak Pain Visual Analog Scale (VAS)
timeFrame: Peak Pain VAS will be the highest rating during each 2 hour study session.
measure: Peak Clinical Opiate Withdrawal Scale (COWS) Rating
timeFrame: Peak COWS rating will be the highest rating during each 2 hour study session.
measure: Peak Subjective Opiate Withdrawal Scale (SOWS) Rating
timeFrame: Peak SOWS rating will be the highest rating during each 2 hour study session.
measure: Peak Increase From Baseline Pupil Diameter
timeFrame: Peak increase from baseline pupil diameter will be the largest increase from baseline pupil diameter measured during each 2 hour study session.
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: D. Andrew Tompkins, MD
role: PRINCIPAL_INVESTIGATOR
References: