Symptom-Inhibited Naloxone Induction (SINI) for Buprenorphine Initiation: A Feasibility Trial

NCT07439549 | Recruiting Phase 4

• 1 other identifier: H25-01585
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical study is to evaluate a new treatment approach called symptom inhibited naloxone induction (SINI) for people with opioid use disorder. In this study, participants will receive small doses of intravenous (IV) naloxone at intervals until they feel mild opioid withdrawal symptoms. At this point, they will be given buprenorphine/naloxone under the tongue to help with the withdrawal symptoms. One hour after, they will receive a injection of long acting buprenorphine under the skin if they choose to. The main questions this study aims to answer are: Is it feasible to use the SINI protocol in inpatient and outpatient settings? Is the SINI protocol safe and tolerable for individuals with opioid use disorder?

Conditions

Opioid Use Disorder

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Enrollment rate

  Number of participants enrolled per month

  Enrollment

• Proportion of ≥8 mg BUP/NLX

  Proportion of enrolled patients who receive ≥8 mg sublingual buprenorphine/naloxone within 1 hour of protocol initiation

  Within 1 hour of first NLX dose

• Proportion of 300 mg BUP-XR

  Proportion of enrolled patients who transition to 300 mg Buprenorphine extended release within 1 hour of first BUP/NLX dose, for those who elect it

  Within 1 hour of first BUP/NLX dose

Secondary Outcomes (13)

• Recruitment

  Through study completion, anticipated to be 6 months

• Unregulated opioid use

  Baseline, Follow up (Day 14 and 28).

• Severity of Opioid Withdrawal (Subjective)

  Intervention (before, after, and during), and follow up (Day 14 and 28)

• Respiratory rate

  Baseline; 2 minutes after each NLX dose; immediately prior to first BUP/NLX dose; 1 hour and 3 hours after first BUP/NLX dose; immediately prior to 300 mg BUP-XR dose; 1 hour, 12 hours, and 24 hours after 300 mg BUP-XR dose

• Heart Rate

  Baseline; 2 minutes after each NLX dose; immediately prior to first BUP/NLX dose; 1 hour and 3 hours after first BUP/NLX dose; immediately prior to 300 mg BUP-XR dose; 1 hour, 12 hours, and 24 hours after 300 mg BUP-XR dose

Study Arms (1)

Intervention

EXPERIMENTAL

Symptom inhibited naloxone induction followed by sublingual buprenorphine/naloxone (2/0.5 mg or 8/2 mg) and extended release buprenorphine injection (300mg/1.5mL)

Drug: Naloxone Hydrochloride 0.4 MG/ML; Drug: Buprenorphine hydrochloride and naloxone hydrochloride dihydrate sublingual tablet (2 mg/0.5 mg and 8 mg/2 mg); Drug: Buprenorphine extended-release injection (300 mg/1.5 mL)

Interventions

Naloxone Hydrochloride 0.4 MG/ML DRUG

0.1 mg naloxone is administered IV every 2 minutes until mild symptoms with COWS ≥ 8 and at least two objective withdrawal signs not attributable to other causes. If fourth and subsequent doses are needed, and withdrawal symptoms are not emerging or are progressing too slowly, the dose may be increased to 0.2 mg based on clinical judgment.

Intervention

Buprenorphine hydrochloride and naloxone hydrochloride dihydrate sublingual tablet (2 mg/0.5 mg and 8 mg/2 mg) DRUG

If the patient opts for BUP/NLX treatment, ≥ 2 mg BUP/NX will be administered under the tongue Q1-3H PRN for withdrawal/pain/cravings. The total dose administered on the first day determines the starting dose for Day 2. If symptoms persist on Day 2, extra doses can be given until stable, and that total amount on Day 2 becomes the new maintenance dose (Maximum dose: 32 mg/day).

Also known as: Buprenorphine/naloxone, Suboxone

Intervention

Buprenorphine extended-release injection (300 mg/1.5 mL) DRUG

If the patient opts for BUP-XR, 1 hour after the administration of sublingual buprenorphine/naloxone, study nurse or physician will subcutaneously administer buprenorphine extended-release injection (300 mg/1.5 mL).

Also known as: Sublocade, subcutaneous buprenorphine

Intervention

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Currently pregnant or breastfeeding.
• COWS ≥ 8

Sponsors & Collaborators

• Pouya Azar: lead
• Vancouver General Hospital: collaborator
• VGH and UBC Hospital Foundation: collaborator
• British Columbia Centre for Excellence in HIV/AIDS: collaborator

Study Sites (2)

Hope to Health Research & Innovation Centre

Vancouver, British Columbia, V6A 1H2, Canada

NOT YET RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, Canada

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Naloxone; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Sublocade

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Pouya Azar, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James Wong, MSc

CONTACT

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

Study Design

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

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: February 27, 2026
• Study Start: April 29, 2026
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

CA (2)