Clinical trial NCT05459402: Divided or Single Exposure (DOSE) Study
Official title: Divided or Single Exposure (DOSE) Study: Randomized Controlled Trial for Pain in Persons Receiving Methadone Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Opioid Use Disorder
Chronic Pain
Methadone
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2022-07-15
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be enrolled for a 14-week Phase II between-group intervention period followed by a 6-month follow-up period with once monthly visits. All participants will be transitioned from liquid to tablet methadone within a 1 to 2-week period before being randomized to treatment as usual versus split daily methadone dosing for a 12-week period. Participants will complete monthly follow-up visits during months 4 - 9.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in worst pain rating- past 24 hour as assessed by the Brief Pain Inventory scale
timeFrame: Week 1 up to week 12
Secondary outcomes:
measure: Change in Pain Tolerance Latency
timeFrame: Weeks 1, 6, and 12
measure: Change in Pain Interference- past 7 days as assessed by Pain-related Disability Scale Total Score
timeFrame: Week 1 up to 12
measure: Change in Opioid Withdrawal Severity- past 24 hours as assessed by the Subjective Opioid Withdrawal Scale
timeFrame: Week 1 up to 12
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Addiction Treatment Services (ATS)
state: Maryland
Study officials:
affiliation: University of Maryland
name: Kelly E Dunn, PhD, M.B.A.
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Denis Antoine, MD
role: PRINCIPAL_INVESTIGATOR
References: