Opioid Use DisorderPhase 4NCT05450718
Low-dose Buprenorphine Initiation for Opioid Use Disorder
A Phase 4 study testing buprenorphine-naloxone in people with Opioid Use Disorder, run by Montefiore Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to test whether low-dose buprenorphine initiation for treatment of opioid use disorder is safe and effective. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- buprenorphine-naloxone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Nov 2024to 30 Jun 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 Diagnostic and Statistical Manual- Version 5 criteria)
- Ability to take sublingual medication
- Willingness to adhere to the assigned buprenorphine initiation regimen
- Fluency in English or Spanish
- For participants of reproductive potential: agreement to use highly effective contraception during study participation
Who cannot join
- Use of FDA-approved medications for opioid use disorder treatment (within 7 days prior to screening), including methadone, buprenorphine, or naltrexone
- Diagnosis of Alcohol Use Disorder, severe or Benzodiazepine Use Disorder, severe (based on Diagnostic and Statistical Manual- Version 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Montefiore Medical Center
The Bronx, New York, 10467
Benjamin T Hayes, MD, MS, MPH, 929-996-3408, bhayes@montefiore.org
Jessica Carter, 718-920-5394
About this study
Official title: A Pilot Randomized Controlled Trial of Low-dose Buprenorphine Initiation for Opioid Use Disorder
The purpose of this study is to test whether low-dose buprenorphine initiation for treatment of opioid use disorder is safe and effective.
Read the 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.
- Conditions
- Opioid Use Disorder
- Being tested
- buprenorphine-naloxone
- Keywords
- micro-induction, microdosing, low-dose initiation, buprenorphine, micro-initiation
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
buprenorphine-naloxoneDrug
Also called buprenorphine microdosing, buprenorphine micro-induction, buprenorphine micro-initiation
Low-dose initiation of buprenorphine-naloxone protocol
buprenorphine-naloxoneDrug
Standard clinical guidelines for a two-day buprenorphine-naloxone initiation
| Study group | Role | What they receive |
|---|---|---|
| Low-dose initiation | Experimental | Participants randomized to low-dose buprenorphine initiation will start low-dose buprenorphine-naloxone (bup-nx) according to an at-home, 8-day protocol (below). Participants in the low-dose buprenorphine 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 Receives: Drug: buprenorphine-naloxone |
| Treatment as usual | Active comparator | Participants randomized to treatment as usual will start buprenorphine-naloxone (bup-nx) following standard clinical guidelines for two-day, at-home initiation. Receives: Drug: buprenorphine-naloxone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment Feasibility: Percentage of subjects assessed who enroll in the clinical trial.
This pilot study is designed to establish the feasibility of a future, full-powered clinical trial. The primary question this study seeks to answer is whether primary care patients with opioid use disorder are willing to enroll in a clinical trial of low-dose inductions. The study will aim to enroll 25% of subjects who are assessed. "Assessed" is defined as having been referred to the study staff. Enrollment is defined as having been randomized to a treatment arm.
Measured: At baseline study visit (time zero)
Secondary outcomes (7)
Protocol Feasibility: Proportion of participants who follow adequate fidelity to the low-dose initiation study protocol.
This pilot study will seek to answer whether participants of a clinical trial adhere to a low-dose buprenorphine-naloxone (bup-nx) initiation protocol. The study aims to achieve 80% of study participants meeting adequate fidelity to the low-dose study protocol. Adequate fidelity is defined as meeting all of the following:
- First dose is a low dose (defined as less than 1-.25mg bup-nx) (yes/no),
- Daily bup-nx dose equivalent to assigned daily dose: For the first 7 days the reported total daily bup-nx dose is within the prespecified assigned daily dose limit,
- Variability: Each day's daily dose is increased from the prior daily dose (within daily limits) (yes/no).
Measured using once daily participant self-report through mobile data collection technology.
Measured: From baseline to day 8
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).
Measured: 2-week study visit
Number of participants retained in buprenorphine treatment at 6 weeks
6-week retention is defined as having an active buprenorphine prescription and buprenorphine-positive UDT at the 6-week visit
Measured: 6-week study visit
Non-prescribed opioid use
The mean number of days of non-prescribed 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 6-week visit (continuous).
Measured: From baseline to 6-week study visit
Withdrawal severity
Measured using the Subjective Opioid Withdrawal Score, a 16-item scale based on symptom severity (from 0=Not at all, to 4=extremely). Multilevel mixed-linear effects models will be used to assess between arms.
Measured: From baseline to 2-week study visit
Precipitated withdrawal
The percentage of participants who experience precipitated withdrawal during the first 2 weeks of initiation. Defined as withdrawal symptoms that get markedly worse within 90 minutes of taking buprenorphine-naloxone dose. Markedly worse will be defined as a change in 10 points on Subjective Opioid Withdrawal Score (SOWS) severity, or as determined by a study clinician. SOWS is a 16-item scale based on symptom severity (from 0=Not at all, to 4=extremely, yielding a possible overall range from 0-64). Precipitated withdrawal is expected only during periods of increasing buprenorphine-naloxone dose titrations: for the low-dose protocol precipitated withdrawal could occur from dose 1 - 13; for the treatment as usual protocol precipitated withdrawal could occur from dose 1 - 5. SOWS will be collected 5 times/day using daily mobile data collection entries.
Measured: From baseline to 2-week study visit
Mild vs Mod-Severe Withdrawal symptoms
The proportion of severe vs mild-moderate buprenorphine-related withdrawal events between study arms will be assessed using the using the Subjective Opioid Withdrawal Score, a 16-item scale based on symptom severity (from 0=Not at all, to 4=extremely). The 16 items are summed with a score of 1-10 representing mild withdrawal, 11-20 as moderate withdrawal, and >/= 21 as severe withdrawal.
Measured: From baseline to 2-week study visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2022
- Study start11 Nov 2024
- Primary completion17 Mar 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- More trials run by Montefiore Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Benjamin T Hayes, MD, MS, MPH, Principal investigator, Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05450718
- Sponsor's protocol ID
- 2022-14185
- Other IDs
- 1K23DA055933
- Status last verified
- Jul 2026
- First submitted
- 22 Jun 2022
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Hayes BT, Sabado A, Minami H, Zhang C, Holm M, Khalid L, Lu TY, Torres-Lockhart K, Fox AD. MiBUP: A pilot randomized controlled trial of low-dose initiation of buprenorphine for opioid use disorder: Design and rationale. Contemp Clin Trials Commun. 2026 Jan 5;49:101594. doi: 10.1016/j.conctc.2026.101594. eCollection 2026 Feb.
PubMed 41567709
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Randomized Controlled Trial of Low-dose Buprenorphine Initiation for Opioid Use Disorder
- ClinicalTrials.gov ID
- NCT05450718
- Acronym / sponsor ID
- 2022-14185
- Conditions
- Opioid Use Disorder
- Keywords
- micro-induction, microdosing, low-dose initiation, buprenorphine, micro-initiation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 11 Nov 2024 (actual)
- Primary completion
- 17 Mar 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 11 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low-dose initiation | Experimental | Drug: buprenorphine-naloxoneParticipants randomized to low-dose buprenorphine initiation will start low-dose buprenorphine-naloxone (bup-nx) according to an at-home, 8-day protocol (below). Participants in the low-dose buprenorphine 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 |
| Treatment as usual | Active comparator | Drug: buprenorphine-naloxoneParticipants randomized to treatment as usual will start buprenorphine-naloxone (bup-nx) following standard clinical guidelines for two-day, at-home initiation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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 Diagnostic and Statistical Manual- Version 5 criteria)
- Ability to take sublingual medication
Key exclusion criteria (7 listed)
- Use of FDA-approved medications for opioid use disorder treatment (within 7 days prior to screening), including methadone, buprenorphine, or naltrexone
- Diagnosis of Alcohol Use Disorder, severe or Benzodiazepine Use Disorder, severe (based on Diagnostic and Statistical Manual- Version 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| buprenorphine-naloxoneAlso: buprenorphine microdosing, buprenorphine micro-induction, buprenorphine micro-initiationLow-dose initiation of buprenorphine-naloxone protocol | Drug | Low-dose initiation |
| buprenorphine-naloxoneStandard clinical guidelines for a two-day buprenorphine-naloxone initiation | Drug | Treatment as usual |
Primary outcome
Recruitment Feasibility: Percentage of subjects assessed who enroll in the clinical trial.
Time frame: At baseline study visit (time zero)
This pilot study is designed to establish the feasibility of a future, full-powered clinical trial. The primary question this study seeks to answer is whether primary care patients with opioid use disorder are willing to enroll in a clinical trial of low-dose inductions. The study will aim to enroll 25% of subjects who are assessed. "Assessed" is defined as having been referred to the study staff. Enrollment is defined as having been randomized to a treatment arm.
7 secondary outcomes
Protocol Feasibility: Proportion of participants who follow adequate fidelity to the low-dose initiation study protocol.
Time frame: From baseline to day 8
Number of participants who uptake buprenorphine treatment at 2 weeks
Time frame: 2-week study visit
Number of participants retained in buprenorphine treatment at 6 weeks
Time frame: 6-week study visit
Non-prescribed opioid use
Time frame: From baseline to 6-week study visit
Withdrawal severity
Time frame: From baseline to 2-week study visit
Precipitated withdrawal
Time frame: From baseline to 2-week study visit
Mild vs Mod-Severe Withdrawal symptoms
Time frame: From baseline to 2-week study visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Derived from this study: PubMed 41567709Hayes BT, Sabado A, Minami H, Zhang C, Holm M, Khalid L, Lu TY, Torres-Lockhart K, Fox AD. MiBUP: A pilot randomized controlled trial of low-dose initiation of buprenorphine for opioid use disorder: Design and rationale. Contemp Clin Trials Commun. 2026 Jan 5;49:101594. doi: 10.1016/j.conctc.2026.101594. eCollection 2026 Feb.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Benjamin T Hayes, MD, MS, MPH principal investigator
Montefiore Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing buprenorphine-naloxone in people with Opioid Use Disorder, run by Montefiore Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Benjamin T Hayes, MD, MS, MPH (4156700850, bhayes@montefiore.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment Feasibility: Percentage of subjects assessed who enroll in the clinical trial. (time frame: At baseline study visit (time zero)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05450718, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.