Microdose Buprenorphine Initiation for Opioid Use Disorder

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test whether low-dose buprenorphine initiation for treatment of opioid use disorder is safe and effective.

Detailed Description
-----------------
After being informed about the study and potential risks, all participants will be given written informed consent. Eligible participants will be randomized in a 1:1 ratio to an 8-day low-dose buprenorphine initiation protocol or treatment as usual, and conduct study visits at baseline and weeks 2 and 4. The investigators will also provide participants with mobile phones to collect real-time data on withdrawal, anxiety, craving and substance use through electronic Ecological Momentary Assessment (EMA) technology.

Official Title
-----------------
Randomized Trial of Buprenorphine Microdose Initiation for Ambulatory Settings

Conditions
-----------------
Opioid Use Disorder

Intervention / Treatment
-----------------
* Drug: buprenorphine-naloxone
* Drug: buprenorphine-naloxone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Any gender, aged 18 years or greater Opioid Use Disorder (based on DSM-5 criteria)56 Ability to take sublingual medication Willingness to adhere to the assigned BUP initiation regimen Fluency in English or Spanish For participants of reproductive potential: agreement to use highly effective contraception during study participation Exclusion Criteria: Use of FDA-approved medications for OUD treatment (within 14 days prior to screening), including methadone, buprenorphine, or naltrexone Diagnosis of Alcohol Use Disorder, severe or Benzodiazepine Use Disorder, severe (based on DSM-5 criteria) Severe untreated mental illness, meaning psychosis or suicidality Presence of an acute or chronic medical condition that would make participation medically hazardous Pregnancy or lactation Known allergic reactions to buprenorphine or naloxone Inability to consent due to cognitive impairment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose initiation<br>Participants randomized to low-dose buprenorphine initiation will start low-dose buprenorphine-naloxone according to an at-home, 8-day protocol (below). Participants in the low-dose BUP initiation arm will be allowed to continue taking the full opioid agonist that they were taking at the time of enrollment until they reach a therapeutic dose of buprenorphine-naloxone. Day 1: 0.5 mg once; Day 2: 0.5 mg every 12 hours; Day 3: 1 mg every 12 hours; Day 4: 2 mg every 12 hours; Day 5: 3mg every 12 hours; Day 6: 4 mg every 12 hours; Day 7: 6 mg every 12 hours; Day 8: 8 mg every 12 hours | Drug: buprenorphine-naloxone<br>* Low-dose initiation of buprenorphine-naloxone protocol<br>* Other names: buprenorphine micro-initiation;|
| Active Comparator: Treatment as usual<br>Participants randomized to treatment as usual will start buprenorphine-naloxone following standard clinical guidelines for two-day, at-home initiation. | Drug: buprenorphine-naloxone<br>* Standard clinical guidelines for a two-day buprenorphine-naloxone initiation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who uptake buprenorphine treatment at 2 weeks | Uptake is defined as having a positive urine drug test (UDT) for buprenorphine at the 2-week study visit (dichotomous, yes/no). | 2-week study visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants retained in buprenorphine treatment at 4 weeks | 4-week retention is defined as having an active buprenorphine prescription and buprenorphine-positive UDT at the 4-week visit | 4-week study visit | 
| Illicit opioid use | Illicit opioid use will be examined as the mean number of days of illicit opioid use, defined as self-reported use of heroin, fentanyl, or non-prescribed opioid analgesics in the prior 14 days using an adapted version of the Addiction Severity Index, will be reported for each arm at the 4-week visit (continuous). | From baseline to 4-week study visit | 
| Proportion of doses of buprenorphine taken according to treatment as usual arm initiation protocol | Measured using once daily participant self-report through Ecological Momentary Assessment technology and defined as the proportion of pre-packaged doses taken each day during the initiation protocol. | From baseline to day 2 | 
| Proportion of doses of buprenorphine taken according to low-dose protocol initiation protocols | Measured using once daily participant self-report through Ecological Momentary Assessment technology and defined as the proportion of pre-packaged doses taken each day during the initiation protocol. | From baseline to day 8 | 
| Withdrawal severity | Investigators will measure the frequency and severity of opioid withdrawal score, measured using the Subjective Opioid Withdrawal Score, a 16-items scaled on symptom severity (scale from 0=Not at all to 4=extremely). Withdrawal events will be classified as mild, moderate, or severe. Investigators will compare the percentage of severe and mild-moderate BUP-related withdrawal events between study arms). | From baseline to 4-week study visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
opioid use disorder, micro-induction, microdosing, low-dose initiation, buprenorphine, micro-initiation