Divided or Single Exposure (DOSE) Study

University of Maryland Baltimore (UMB)

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Opioid Use Disorder; Chronic Pain; Methadone

Treatments: Drug: Methadone (100% dose); Drug: Methadone (50% dose)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05459402

IRB00318642

1R01DA056045 (U.S. NIH Grant/Contract)

1R01DA056045-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This study will evaluate whether once versus twice daily dosing of methadone will be an effective method for managing comorbid pain and opioid use disorder.

Full description

This study follows a successfully completed project (NCT03254043) to now pursue the investigators overarching goal of optimizing methadone dosing as a method for managing comorbid chronic pain and opioid use disorder (OUD) among persons receiving methadone for the treatment of OUD. Up to 62% of persons maintained on methadone for OUD experience clinically significant pain, versus 31% in the general population. Pain in methadone-maintained persons (MMP) is associated with poor OUD treatment outcomes and severe distress. No effective treatment for comorbid pain and OUD currently exists; though preclinical and human data suggest divided methadone dosing may be a more optimal strategy for managing pain than once daily dosing, this has never been empirically examined. This study will evaluate an intervention for comorbid chronic pain among MMP using a Phase II double-blind, randomized, placebo-controlled comparison of treatment as usual (TAU) versus split daily methadone dosing for 12-weeks. Methadone will be remotely managed via an electronic pillbox. Outcomes will include weekly assessments of pain and OUD outcomes, ecological momentary assessment of pain before and after dosing, and point-prevalence measures of laboratory-induced pain to explore mechanism of effects. If effective, this approach could transform the care of MMP with pain because it would be feasible to implement within the operational structure of a methadone clinic and would impose low provider burden. Results could provide a high magnitude treatment for the substantial number of MMP who experience daily pain with no reliable form of treatment.

Enrollment: 150 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged 18 years of age or older
• Currently receiving methadone for treatment of OUD for >90 days and have been consuming the same dose for >30 days
• Have previously received a take-home dose of methadone as part of routine care
• Willing to comply with study schedule
• Report pain (specific definition blinded)
• Have a cellular phone or be willing to carry phone provided by the study during one phase of the study

Exclusion criteria

• Pregnant
• Presence of acute medical problem that requires immediate and intense medical management
• Presence of a serious and unstable mental illness that interferes with provision of voluntary informed consent and/or adherence to study visits
• Plans to leave methadone treatment during the study period
• Maintained on a dose of methadone that would prevent effective splitting of doses
• Currently receiving split doses of methadone
• Currently receiving treatment for pain for which the split-dosing of methadone is judged by medical staff to be contraindicated or otherwise interfere with study conduct or integrity
• Does not meet criteria for mild-severe disability (definition blinded)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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150 participants in 2 patient groups

Treatment as Usual (TAU)

Active Comparator group

Description:

Participants in treatment as usual group will receive 100% active methadone in AM + placebo in PM.

Treatment:

Drug: Methadone (100% dose)

Split-dosing

Experimental group

Description:

Participants in split dosing group will receive 50% active methadone + placebo twice daily.

Treatment:

Drug: Methadone (50% dose)