Symptom‑inhibited naloxone induction to start buprenorphine/naloxone

Symptom-inhibited Naloxone Induction (SINI) to Initiate Buprenorphine/Naloxone and Buprenorphine Extended-release for Opioid Use Disorder: A Single-arm Feasibility Trial

This study will try giving small, repeated IV doses of naloxone to trigger brief mild withdrawal so adults with opioid use disorder can begin buprenorphine safely, with an option for a long‑acting buprenorphine injection.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: University of British Columbia (Academic / other)
• Locations: 2 sites (Vancouver, British Columbia and 1 other locations)
• Trial ID: NCT07439549 on ClinicalTrials.gov

What this trial studies

This is a prospective, single‑arm, open‑label feasibility study enrolling 12 adults with opioid use disorder who need to start opioid agonist therapy. Clinicians will administer 0.1–0.2 mg IV naloxone every 2 minutes until the patient reaches mild withdrawal (COWS ≥8 with at least two objective signs), then give ≥8 mg sublingual buprenorphine/naloxone and offer a 300 mg subcutaneous extended‑release buprenorphine injection one hour later if withdrawal remains controlled. The protocol collects substance use history, treatment and harm‑reduction utilization, serial COWS/SOWS scores, vital signs, and adverse events to measure feasibility, safety, and tolerability. The intervention is tested in both inpatient and outpatient settings at Vancouver sites with monitored IV access and observation.

Who should consider this trial

Good fit: Adults (≥19 years) with DSM‑5 opioid use disorder who have a clinical indication for buprenorphine, can tolerate brief mild precipitated withdrawal, can maintain IV access, and can provide informed consent.

Not a fit: People who cannot tolerate even short-lived withdrawal, cannot have or maintain IV access, have contraindications to naloxone or buprenorphine, or cannot attend the Vancouver sites are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, SINI could enable faster, more predictable buprenorphine starts—including for people exposed to fentanyl—and increase access to opioid agonist therapy.

How similar studies have performed: The SINI protocol itself is novel and has limited prior data, though related approaches (microdosing and rapid/high‑dose inductions) have shown some promising but not definitive results.

Eligibility criteria

Inclusion Criteria:

To be eligible for this study, participants must fulfill all the following inclusion criteria:

* 19 years of age or older.
* Opioid use disorder as confirmed by DSM 5 diagnostic criteria.
* Clinical indication to start OAT with buprenorphine.
* Willingness to tolerate mild opioid withdrawal precipitated by naloxone, expected to last less than 20 minutes.
* Willing and able to have and maintain IV access for the duration of the SINI
* If of childbearing potential and elected BUP-XR, agree to use an effective method of birth control.

  o Highly effective methods of birth control include hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy and tubal ligation. Effective methods include barrier methods of contraception (e.g., male condom, female condom, cervical cap, diaphragm, contraceptive sponge).
* Willing and able to provide written informed consent for study participation.

Exclusion Criteria:

If participants meet any of the following exclusion criteria, they will be excluded from participation in the study:

* Diagnosis of severe medical or psychiatric conditions contraindicated for naloxone or buprenorphine.
* Concomitant use of medications with drug-drug interactions with buprenorphine, unless alternative treatment options are less appropriate and a risk-benefit assessment has been discussed and recommended by the participant's healthcare team.

  o Examples include, but are not limited to: benzodiazepines and non-benzodiazepine central nervous system depressants, naltrexone, CYP3A4 inhibitors and inducers, serotonergic drugs, monoamine oxidase inhibitors, QTc interval-prolonging drugs, diuretics, anticholinergics, and antiretrovirals.
* Known allergy or sensitivity to naloxone or buprenorphine.
* Use of BUP/NLX within the past 9 days.
* Use of BUP-XR within the past 43 weeks.
* Previous participation in this study (previous receipt of SINI in a clinical setting is not exclusionary).
* Currently pregnant or breastfeeding.
* COWS ≥ 8

Where this trial is running

Vancouver, British Columbia and 1 other locations

• Hope to Health Research & Innovation Centre — Vancouver, British Columbia, Canada (Not_yet_recruiting)
• Vancouver General Hospital — Vancouver, British Columbia, Canada (Recruiting)

Study contacts

• Principal investigator: Pouya Azar, MD — Department of Psychiatry, Faculty of Medicine, University of British Columbia and Vancouver General Hospital
• Study coordinator: James Wong, MSc

Conditions Opioid Use Disorder; Opioid Agonist Therapy; Buprenorphine; Fentanyl; Naloxone; Medications for Opioid Use Disorder; Buprenorphine Extended-Release