Finding the right methadone loading dose for people with fentanyl opioid use disorder

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a participant- and assessor-blinded, randomized, phase 1 dose-finding study using a Bayesian optimal interval (BOIN) design to identify safe loading doses of methadone for people with fentanyl-positive opioid use disorder. Investigators plan to enroll 24 participants who will be admitted to a research unit for monitored methadone initiation and randomized to standard initiation or one of four loading-dose regimens. The study uses careful monitoring for safety and tolerability during the initiation period and adapts dose decisions based on observed outcomes. The intervention is oral methadone hydrochloride and participants must be willing to start outpatient methadone at specified local clinics.

Why it matters

Who can join: the full rules

Inclusion criteria:

1. Male, female, transgender, or non-binary, aged 18 years or older
2. DSM-5 criteria for opioid use disorder, moderate-severe
3. Fentanyl positive urine drug test
4. Able to provide a dated \& written informed consent in English prior to the conduct of any study related procedures
5. Stated willingness to comply with all study procedures and availability for the duration of the study
6. Ability to take oral medication and be willing to adhere to the dosage regimen
7. Interest in starting methadone treatment for opioid use disorder at a partner location
8. Reliable access to a working phone

Exclusion criteria:

1. Hypersensitivity or allergy to methadone that is previously documented
2. Pregnancy or actively lactating (with urine pregnancy test performed on screening and repeated on admission to the unit prior to randomization)
3. Taking medications for opioid use disorder, per self-report or per urine drug testing detection of buprenorphine or methadone
4. At risk of benzodiazepine or alcohol withdrawal as defined by: prior benzodiazepine or alcohol withdrawal in the past 3 months, current daily use of benzodiazepines or alcohol, or DSM-5 criteria for hypnotic-sedative or alcohol use disorder
5. At risk of severe medetomidine withdrawal based on: serum or urine testing for medetomidine (if available), prior withdrawal syndrome requiring intensive care unit admission within past 6 months, and/or severe nausea/vomiting during first 4 hours of withdrawal, at the discretion of the study physicians
6. At risk for methadone-induced QT-prolongation: prolonged QTc on screening or admission EKG (greater than 450ms in men, greater than 460ms in women), history of QT prolongation, previously documented long QT syndrome, history of ventricular arrhythmia (e.g., torsades de pointes), history of cardiac hypertrophy, history of cardiac conduction abnormalities, taking medications that affect cardiac conduction (at study physician discretion; including but not limited to: amiodarone, flecainide, sotalol, azithromycin, ciprofloxacin, levofloxacin, citalopram, escitalopram, hydroxychloroquine, chlorpromazine, haloperidol, donepezil, ibogaine, cilostazol), serum potassium concentration less than 3.5 mg/dL, or serum magnesium concentration less than 1.7 mg/dL.
7. Significant hepatic dysfunction, defined as: AST and/or ALT 3x upper limit of normal, or total bilirubin 1.5x upper limit of normal
8. Significant renal dysfunction, defined as: eGFR less than or equal to 60 mL/min
9. Chronic hypotension (\<90/50 mmHg) or episodic symptomatic hypotension, defined as a history of active or recurrent orthostatic hypotension or syncope
10. Significant pulmonary disease, defined as: baseline SpO2 \<95% on screening or admission, requiring oxygen at home (chronically or at bedtime), or COPD with modified MRC Dyspnea Scale greater than 2 ("I stop for breath after walking about one city block")
11. Suspected gastrointestinal obstruction, per medical history
12. 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
13. Pending legal action that could prohibit participation and/or compliance in study procedures
14. Presence of any other psychiatric and/or medical disorder that, in the opinion of the PI, will interfere with completion of the study or place the patient at heightened risk through participation in the study.

Where it's running

• Penn Center for Studies of Addiction (CSA)
  Philadelphia, Pennsylvania, United States Recruiting

Study contacts

• Study coordinator: Ashish P Thakrar, MD, MS
• Email: apthakrar@pennmedicine.upenn.edu
• Phone: (215) 662-2250

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.