Clinical trial NCT06877858: MethaLoad Dose-Finding Study
Official title: A Dose-Finding Study of Methadone Loading Dose Initiation for Opioid Use Disorder with Fentanyl Use
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Opioid Use Disorder (OUD)
Keywords: methadone
fentanyl
opioid use disorder
opioid addiction
opiate addiction
OUD
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2025-03-14
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Bayesian Optimal Interval Design (BOIN) for dose-finding studies
Primary purpose: TREATMENT

Brief summary: The goal of this proposal is to develop a "loading dose" approach to starting methadone to treat fentanyl opioid use disorder (OUD). We aim to conduct an assessor-blinded dose-finding study of 24 participants with fentanyl OUD recruited to a research unit for monitored methadone dosing. Participants will be randomized to standard methadone initiation vs. one of three loading dose approaches. The primary goal is to identify the maximum tolerated methadone loading dose appropriate for future study.


Eligibility criteria: Inclusion Criteria:

1. Able to provide a dated written informed consent in English prior to the conduct of any study related procedures
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male, female, transgender, or non-binary aged 18 or older
4. In good general health as evidenced by medical history.
5. Fentanyl positive urine drug test
6. Ability to take oral medication and be willing to adhere to the dosage regimen
7. For females of reproductive potential: negative urine pregnancy test on screening and on admission
8. DSM-5 criteria for opioid use disorder, moderate to severe
9. Interest in starting methadone treatment for opioid use disorder at Merakey Parkside (our partner outpatient treatment program where we will send patients on discharge from the study)

Exclusion Criteria:

1. Previously documented hypersensitivity or allergy to methadone
2. Prolonged QTc (=450ms in men, =460ms in women), previously documented long QT syndrome, history of QT prolongation, or history of ventricular arrhythmia (e.g., torsades de pointes)
3. Pregnancy or lactation
4. DSM-5 criteria for benzodiazepine or alcohol use disorder
5. Urine drug testing at screening positive for buprenorphine and/or methadone
6. AST and/or ALT 3x upper limit of normal or total bilirubin or equal to 1.5x upper limit of normal
7. eGFR less than or equal to 60 mL/min
8. Chronic hypotension (\<90/50 mmHg) or episodic symptomatic hypotension (history of active or recurrent orthostatic hypotension or syncope).
9. Significant chronic pulmonary disease: COPD with modified MRC Dyspnea Scale \>=3 ("I stop for breath after walking about one city block") or requiring oxygen (chronically or at bedtime)
10. Active, chronic use of the CYP3A4-inducers or -inhibitors rifampin, phenytoin, St John's wort, phenobarbital, carbamazepine, voriconazole, efavirenz, nelfinavir, nevirapine, ritonavir, and lopinavir+ritonavir, abacavir, or amprenavir
11. Significant medical symptoms, psychiatric symptoms, or dementia that, in the opinion of the investigators, would preclude compliance with the protocol, cooperation in the study, obtaining informed consent, or ability to safely participant in the study
12. Pending legal action that could prohibit participation and/or compliance in study procedures

Primary outcomes:
measure: Dose-limiting toxicity rate
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
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