Methadone Rapid Restart

NCT07546396 | Not Yet Recruiting Phase 4

• 1 other identifier: H25-03989
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The usual treatment for opioid use disorder (OUD) is opioid agonist therapy (OAT) with either methadone or buprenorphine. These treatments are well-established, reduce the risk of fatal overdoses, and are considered the standard approach. However, current methadone guidelines were developed when most people were using heroin, which is far less potent than today's unregulated/illicit fentanyl supply. As a result, people who use fentanyl often need higher doses to feel stable. Because methadone must be started at low doses and increased slowly, it can take weeks before someone reaches an effective dose. This process becomes even longer when doses are missed, since treatment often needs to be restarted at a lower level. The Methadone Rapid Restart is a newer strategy designed to take ongoing fentanyl use into account. Early clinical experience and modelling suggest that many people who use fentanyl have high opioid tolerance and may be able to return to their previous stable methadone dose even after several missed days, without added safety risk. This approach has shown promise in small clinical settings, but it is not yet known whether it provides better outcomes than the standard methadone titration used today. This study will be testing whether this protocol to help rapidly restart people on Methadone is acceptable for patients and use the learning to guide a subsequent larger clinical trial.

Conditions

Opioid Use Disorder

Keywords

Opioid Use Disorder; Opiate Agonist Therapy; Methadone; Medications for Opiate Use Disorder

Outcome Measures

Primary Outcomes (2)

• Enrollment rate

  Number of participants enrolled per month

  Enrollment

• Patient Satisfaction

  At the end of the follow up period participants will be asked, "Overall, how satisfied were you with the methadone restart protocol?" The response will be recorded on a 7-point scale: 1=extremely dissatisfied; 2= very dissatisfied; 3= somewhat dissatisfied; 4=neither satisfied nor dissatisfied; 5=somewhat satisfied; 6=very satisfied; 7=extremely satisfied.

  Assessed retrospectively at the end of 7 day follow up period.

Secondary Outcomes (11)

• Recruitment

  Through study completion, anticipated to be 12 months

• Level of sedation

  Baseline, Intervention (1, 2, and 3 hour post-dose) and follow up (Day 1, 3 and 7)

• Blood Pressure

  Baseline, intervention (1,2, and 3 hour post methadone dose), and follow up (Day 1, 3, and 7)

• Oxygen saturation

  Baseline, intervention (1, 2, and, 3 hour post dose) and follow up (Day 1, 3, and 7)

• Respiratory rate

  Baseline, intervention (1, 2 and 3 hour after post methadone dose), and follow up (Day 1, 3, and 7)

Study Arms (2)

Methadone rapid restart for participants on methadone maintenance treatment

EXPERIMENTAL

Participants who have missed 4-8 doses of methadone, but were on maintenance treatment with methadone for opioid use disorder at a stable dose for at least 5 consecutive days prior to discontinuing, with allowance for a maximum of 1 missed dose within that 5-day period. These participants will be re-initiated on 100% of their most recent methadone dose.

Drug: Methadone

Methadone rapid restart for participants being titrated on methadone

EXPERIMENTAL

Participants who have missed 4-8 doses of methadone, but were being titrated on methadone prior to discontinuation such that they were on their most recent dosage for less than 5 days but received at least 5 consecutive days of methadone between the prior two dosages (with a maximum of 1 missed dose in that period) be. These participants will be restarted on the lower of their two most recent dosages.

Drug: Methadone

Interventions

Methadone DRUG

Participants who meet study inclusion criteria and have no exclusion criteria, who have missed 4-8 doses of methadone will, be administered methadone according to the stratification below and will continue the same dose for the 7 day follow up. * Arm 1: Previous maintenance treatment with methadone for opioid use disorder at a stable dose for at least 5 consecutive days prior to discontinuing, with allowance for a maximum of 1 missed dose within that 5-day period. These participants will be re-initiated on 100% of their most recent methadone dose. * Arm 2: Participant was being titrated on methadone prior to discontinuation such that they were on their most recent dosage for less than 5 days but received at least 5 consecutive days of methadone between the prior two dosages (with a maximum of 1 missed dose in that period) be. These participants will be restarted on the lower of their two most recent dosages.

Also known as: Metadol-D, Methadose

Methadone rapid restart for participants being titrated on methadone; Methadone rapid restart for participants on methadone maintenance treatment

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 19 years or older
• Opioid use disorder (OUD) of any severity by DSM-5 TR Clinical Diagnostic criteria \[American Psychiatric Association, 2022\]
• Previously 'stable' on methadone as per the below definitions:
• Previous maintenance treatment with methadone for opioid use disorder at a stable dose for at least 5 consecutive days prior to discontinuing, with allowance for a maximum of 1 missed dose within that 5-day period.
• Participants who were being titrated on methadone for opioid use disorder prior to discontinuation. If participants were on the most recent dose for less than 5 days, they can be restarted on the prior dose providing they cumulatively received 5 consecutive doses (with a maximum of 1 missed dose in that period) between the two most recent dosages.
• Missed 4-8 doses of methadone in a row leading up to intake assessment.
• Participant able to provide baseline opiate use history as per opiate use screening questions in Appendix A. This must provide an estimate of opiate use prior to stopping methadone and change in use since stopping.
• Self-reported increased use of fentanyl since stopping methadone.
• No significant change in opiate withdrawal symptoms as compared to when on methadone, based on self-report and examination.
• Urine drug test (UDT) positive for fentanyl at screening or within 24 hours prior to re-initiating methadone.
• Participant wishes to continue methadone maintenance treatment.
• If applicable the participant must be willing to complete a urine pregnancy test to ensure they are not currently pregnant.
• Participants will require a baseline ECG that demonstrates a QTc \< 500ms.
• For participants from VGH study site specifically:
• must be admitted to either psychiatry or CTU, ideally with planned admission of at least 3 days.

You may not qualify if:

• COWS score of 8 or more at the time of clinician assessment
• Self-reported Opioid overdose or naloxone administration since methadone discontinuation or during the 5 days prior to methadone discontinuation
• Self-reported New cardiac disease diagnosis since methadone discontinuation
• Self-reported Intolerable side effects reported when taking methadone
• Individuals who are pregnant (urine pregnancy test) or breast-feeding (self-reported)
• Use of buprenorphine-naloxone (Suboxone®, Sublocade®, Butrans ®) within the previous 3 days (self-reported)
• Participants with a QTc interval \>500 msec on the screening ECG

Sponsors & Collaborators

• Pouya Azar: lead

Study Sites (1)

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1N1, Canada

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Methadone

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals

Study Officials

• Pouya Azar

  Department of Psychiatry, Faculty of Medicine, University of British Columbia and Vancouver General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James Wong

CONTACT

(604) 875-5823; james.wong@vch.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: April 22, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

CA (1)