Substance Use DisordersPhase 4Micro-bupeNCT05118204
Randomized Trial of Buprenorphine Microdose Inductions During Hospitalization
A Phase 4 study testing BUP microdose induction, TAU and Linkage to outpatient BUP treatment in people with Substance Use Disorders and Opioid-use Disorder, run by Montefiore Medical Center at 1 site in United States.
Trial summary
Investigators will test a novel protocol for starting BUP (buprenorphine-naloxone) treatment. The BUP microdose induction protocol has participants start very low doses of BUP without stopping other opioids that they are taking. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Substance Use Disorders, Opioid-use Disorder, Chronic Pain
- What is being tested?
- BUP microdose induction, TAU and Linkage to outpatient BUP treatment
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Sep 2022to 9 Apr 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Age > 18 years
- Opioid misuse or OUD
- Chronic pain
- Currently taking opioids
- Fluency in English or Spanish
- Planned hospitalization for ≥ 48 hours
Who cannot join
- Current OUD treatment (BUP, methadone, naltrexone)
- Severe alcohol or benzodiazepine use disorder
- Hypersensitivity to BUP or naloxone
- Pain due to malignancy
- Severe untreated mental illness (suicidality, psychosis)
- Pregnancy
- Unable to consent due to pain or cognitive impairment
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Medical Center
The Bronx, New York, 10467
About this study
Investigators will test a novel protocol for starting BUP (buprenorphine-naloxone) treatment. The BUP microdose induction protocol has participants start very low doses of BUP without stopping other opioids that they are taking. The treatment as usual (TAU) has participants stop other opioids and experience opioid withdrawal before starting BUP. Investigators propose to test BUP microdose inductions vs. TAU in a randomized controlled trial.
Read the detailed description
Investigators will conduct a hybrid type 1 effectiveness-implementation study, using a pragmatic, open-label, randomized controlled trial (RCT). Investigators will randomize 270 hospitalized patients with (a) chronic pain and (b) opioid misuse or opioid use disorder (OUD) to a 5-day BUP microdose induction protocol (without stopping full agonists) or 2-day standard induction (with stopping full agonists), and then link participants to outpatient BUP treatment when they are released from the hospital. Study assessment visits will occur at baseline, 1 week, and 1, 3, and 6 months. Assessments will include interviews and urine drug tests to determine whether participants start BUP, continue BUP, have improvements in pain and decrease illicit opioid use. During induction and 3-months of follow-up, investigators will also collect data on mobile devices to assess opioid withdrawal, opioid craving, pain, and anxiety. These data will allow investigators to assess whether BUP microdosing targets of engagement-opioid- and pain-related symptoms-mediate OUD outcomes. Exploratory analyses will also examine pain as a trigger for opioid relapse.
Aim 1: To test the effectiveness of BUP microdose induction (vs. TAU) on OUD outcomes.
H1: The microdose arm (vs. TAU) will have better BUP treatment uptake and retention, and less illicit opioid use.
H2: Improvements in H1 will be mediated by opioid- and pain-related symptoms.
Aim 2: To test the effectiveness of microdosing (vs. TAU) on pain outcomes. H3: The microdose arm (vs. TAU) will have less pain intensity and interference, and improved quality of life.
H4: Improvements in H3 will be mediated by OUD outcomes.
Aim 3: To inform future implementation and dissemination efforts, investigators will:
3a) Examine factors influencing reach, adoption, implementation, and maintenance of BUP microdosing. Investigators will use qualitative and quantitative methods to describe multi-level factors influencing these domains; 3b) Calculate the cost and examine cost-effectiveness of BUP microdosing. H5: Compared with TAU, BUP microdosing will be cost-effective from a societal and a health sector perspective.
- Conditions
- Substance Use Disorders, Opioid-use Disorder, Chronic Pain
- Being tested
- BUP microdose induction, TAU, Linkage to outpatient BUP treatment
- Medical subject headings
- Substance-Related Disorders, Opioid-Related Disorders, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BUP microdose inductionDrug
Participants will be started on a 5-day BUP microdose induction protocol (without stopping full agonists).
Day 1: participants will receive buprenorphine (Belbuca) 225 mcg mg every 12 hours Day 2: participants will receive buprenorphine (Belbuca) 450 mcg every 8 hours Day 3: participants will receive buprenorphine-naloxone 2-0.5 mg every 8 hours Day 4: participants will receive buprenorphine-naloxone 4-1 mg every 8 hours Day 5: participants will receive buprenorphine-naloxone 8-2 mg every 12 hours
TAUDrug
2-day standard BUP induction protocol (with stopping full agonists) Day 1: hold all opioids Day 2: buprenorphine-naloxone 2-0.5 mg every 6 hours Day 3: buprenorphine-naloxone 8-2 mg every 12 hours
Linkage to outpatient BUP treatmentBehavioural
Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center
| Study group | Role | What they receive |
|---|---|---|
| BUP microdose induction | Experimental | Participants in this arm will receive a novel BUP microdose induction protocol. Receives: Drug: BUP microdose induction; Behavioral: Linkage to outpatient BUP treatment |
| Treatment As Usual (TAU) | Active comparator | Participants in this arm will receive standard BUP induction protocol. Receives: Drug: TAU; Behavioral: Linkage to outpatient BUP treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
BUP Treatment Uptake
The percentage of participants who start BUP treatment, defined as receiving BUP 7 days after the baseline visit, will be reported for each arm.
Measured: 7 days
Secondary outcomes (4)
Illicit Opioid Use
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 30 days based on the Addiction Severity Index, will be reported for each arm.
Measured: 1, 3, and 6 months
BUP Retention in Care
The number/percentage of participants who are retained in BUP treatment, defined as having a BUP prescription written 180-210 days (6-month retention) after enrollment, will be reported for each arm.
Measured: 1, 3, and 6 months
Pain Intensity
Mean pain intensity score, measured using the Brief Pain Inventory (BPI), will be reported for each study arm. The pain intensity score has 4 items that are each rated on a scale from 0 (low intensity) to 10 (high intensity). The score reported is the average score from the 4-items also reported on a scale of 0-10.
Measured: 3 months
Pain Interference
Mean pain interference score, measured using the pain interference scale from the BPI, which is a 7-item instrument measuring the impact of pain on daily activities and physical functioning, will be reported for each study arm. Each item is rated on a scale from 0 (low interference) to 10 (high interference). The score reported is the average score from the 7-items also reported on a scale of 0-10.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2021
- Study start29 Sep 2022
- Primary completion23 Oct 2024
- Study completion9 Apr 2025
Why it stopped: Difficulty recruiting and enrolling participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Substance Use DisordersStudies 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
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), Weill Medical College of Cornell University, Wake Forest University
- Responsible party
- Sponsor
- Investigators
- Aaron Fox, MD, Principal investigator, Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05118204
- Sponsor's protocol ID
- 2021-13311
- Other IDs
- 1RM1DA055437-01
- Acronym
- Micro-bupe
- Status last verified
- Apr 2026
- First submitted
- 23 Sep 2021
- Last updated
- 8 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Buprenorphine Microdose Inductions During Hospitalization
- ClinicalTrials.gov ID
- NCT05118204
- Acronym / sponsor ID
- Micro-bupe / 2021-13311
- Conditions
- Substance Use Disorders, Opioid-use Disorder, Chronic Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty recruiting and enrolling participants
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), Weill Medical College of Cornell University, Wake Forest University
- Study start
- 29 Sep 2022 (actual)
- Primary completion
- 23 Oct 2024 (actual)
- Study completion
- 9 Apr 2025 (actual)
- First posted
- 11 Nov 2021 (actual)
- Results
- Posted 31 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigators will test a novel protocol for starting BUP (buprenorphine-naloxone) treatment. The BUP microdose induction protocol has participants start very low doses of BUP without stopping other opioids that they are taking. The treatment as usual (TAU) has participants stop other opioids and experience opioid withdrawal before starting BUP. Investigators propose to test BUP microdose inductions vs. TAU in a randomized controlled trial.
Detailed description
Investigators will conduct a hybrid type 1 effectiveness-implementation study, using a pragmatic, open-label, randomized controlled trial (RCT). Investigators will randomize 270 hospitalized patients with (a) chronic pain and (b) opioid misuse or opioid use disorder (OUD) to a 5-day BUP microdose induction protocol (without stopping full agonists) or 2-day standard induction (with stopping full agonists), and then link participants to outpatient BUP treatment when they are released from the hospital. Study assessment visits will occur at baseline, 1 week, and 1, 3, and 6 months. Assessments will include interviews and urine drug tests to determine whether participants start BUP, continue BUP, have improvements in pain and decrease illicit opioid use. During induction and 3-months of follow-up, investigators will also collect data on mobile devices to assess opioid withdrawal, opioid craving, pain, and anxiety. These data will allow investigators to assess whether BUP microdosing targets of engagement-opioid- and pain-related symptoms-mediate OUD outcomes. Exploratory analyses will also examine pain as a trigger for opioid relapse.
Aim 1: To test the effectiveness of BUP microdose induction (vs. TAU) on OUD outcomes.
H1: The microdose arm (vs. TAU) will have better BUP treatment uptake and retention, and less illicit opioid use.
H2: Improvements in H1 will be mediated by opioid- and pain-related symptoms.
Aim 2: To test the effectiveness of microdosing (vs. TAU) on pain outcomes. H3: The microdose arm (vs. TAU) will have less pain intensity and interference, and improved quality of life.
H4: Improvements in H3 will be mediated by OUD outcomes.
Aim 3: To inform future implementation and dissemination efforts, investigators will:
3a) Examine factors influencing reach, adoption, implementation, and maintenance of BUP microdosing. Investigators will use qualitative and quantitative methods to describe multi-level factors influencing these domains; 3b) Calculate the cost and examine cost-effectiveness of BUP microdosing. H5: Compared with TAU, BUP microdosing will be cost-effective from a societal and a health sector perspective.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BUP microdose induction | Experimental | Drug: BUP microdose induction, Behavioral: Linkage to outpatient BUP treatmentParticipants in this arm will receive a novel BUP microdose induction protocol. |
| Treatment As Usual (TAU) | Active comparator | Drug: TAU, Behavioral: Linkage to outpatient BUP treatmentParticipants in this arm will receive standard BUP induction protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age > 18 years
- Opioid misuse or OUD
- Chronic pain
- Currently taking opioids
- Fluency in English or Spanish
Key exclusion criteria (7 listed)
- Current OUD treatment (BUP, methadone, naltrexone)
- Severe alcohol or benzodiazepine use disorder
- Hypersensitivity to BUP or naloxone
- Pain due to malignancy
- Severe untreated mental illness (suicidality, psychosis)
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 |
|---|---|---|
| BUP microdose inductionParticipants will be started on a 5-day BUP microdose induction protocol (without stopping full agonists). Day 1: participants will receive buprenorphine (Belbuca) 225 mcg mg every 12 hours Day 2: participants will receive buprenorphine (Belbuca) 450 mcg every 8 hours Day 3: participants will receive buprenorphine-naloxone 2-0.5 mg every 8 hours Day 4: participants will receive buprenorphine-naloxone 4-1 mg every 8 hours Day 5: participants will receive buprenorphine-naloxone 8-2 mg every 12 hours | Drug | BUP microdose induction |
| TAU2-day standard BUP induction protocol (with stopping full agonists) Day 1: hold all opioids Day 2: buprenorphine-naloxone 2-0.5 mg every 6 hours Day 3: buprenorphine-naloxone 8-2 mg every 12 hours | Drug | Treatment As Usual (TAU) |
| Linkage to outpatient BUP treatmentParticipants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center | Behavioural | BUP microdose induction, Treatment As Usual (TAU) |
Primary outcome
BUP Treatment Uptake
Time frame: 7 days
The percentage of participants who start BUP treatment, defined as receiving BUP 7 days after the baseline visit, will be reported for each arm.
4 secondary outcomes
Illicit Opioid Use
Time frame: 1, 3, and 6 months
BUP Retention in Care
Time frame: 1, 3, and 6 months
Pain Intensity
Time frame: 3 months
Pain Interference
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Aaron Fox, MD 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 BUP microdose induction, TAU and Linkage to outpatient BUP treatment in people with Substance Use Disorders and 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 6 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: stopped early, as of the sponsor's last update on 8 May 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?
Yes. Results are posted in the registry (first posted 31 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BUP Treatment Uptake (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 May 2026; AzTrials last refreshed its copy on 6 Nov 2026.