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| ID | Type | Description | Link |
|---|---|---|---|
| 1RM1DA055437-01 | U.S. NIH Grant/Contract | View source |
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Difficulty recruiting and enrolling participants
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
| Weill Medical College of Cornell University | OTHER |
| Wake Forest University | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BUP microdose induction | Experimental | Participants in this arm will receive a novel BUP microdose induction protocol. |
|
| Treatment As Usual (TAU) | Active Comparator | Participants in this arm will receive standard BUP induction protocol. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BUP microdose induction | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 1, 3, and 6 months |
| BUP Retention in Care |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Aaron Fox, MD | Montefiore Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Montefiore Medical Center | The Bronx | New York | 10467 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | BUP Microdose Induction | Participants in this arm will receive a novel Buprenorphine (BUP) microdose induction protocol. BUP microdose induction: 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 Linkage to outpatient BUP treatment: Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center |
| FG001 | Treatment As Usual (TAU) | Participants in this arm will receive standard BUP induction protocol. Treatment As Usual (TAU): 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 treatment: Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | BUP Microdose Induction | Participants in this arm will receive a novel BUP microdose induction protocol. BUP microdose induction: 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 Linkage to outpatient BUP treatment: Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 7 days |
|
Up to approximately 6 months (24 weeks)
A structured form was used to collect adverse event information at week 1, 4, 12, 24 study visits. A researcher asked participants whether they had experienced: abscess, asthenia, chills, fever, flu syndrome, headache, infection, injury/accident, pain, abdominal pain, back pain, withdrawal syndrome, constipation, diarrhea, dyspepsia, nausea, vomiting, anxiety, depression, dizziness, insomnia, nervousness, somnolence, cough, pharyngitis, rhinitis, sweating, lacrimation, vasodilation, fatigue.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BUP Microdose Induction | Participants in this arm will receive a novel BUP microdose induction protocol. BUP microdose induction: 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 Linkage to outpatient BUP treatment: Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization | Surgical and medical procedures | Systematic Assessment | Participants self-reported whether they were admitted to the hospital for any medical or surgical reason. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abscess | Infections and infestations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Aaron Fox | Albert Einstein College of Medicine | 718-920-7173 | adfox@montefiore.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 2, 2022 | Oct 10, 2025 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 24, 2024 | Jun 6, 2025 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D009293 | Opioid-Related Disorders |
| D059350 | Chronic Pain |
| ID | Term |
|---|---|
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
| D000079524 | Narcotic-Related Disorders |
| D010146 | Pain |
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|
| TAU | Drug | 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 treatment | Behavioral | Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center |
|
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. |
| 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. | 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. | 3 months |
| BG001 | Treatment As Usual (TAU) | Participants in this arm will receive standard BUP induction protocol. TAU: 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 treatment: Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Opioid Use Disorder status | Participants were placed in 2 categories: a) opioid use disorder moderate or severe; b) opioid use disorder mild or opioid misuse. Opioid use disorder (OUD) was defined by Diagnostic and Statistical Manual, version 5 criteria based on number of criteria met (2-3 criteria = OUD mild, 4-5 criteria = OUD moderate, 6+ criteria = OUD severe). Opioid misuse was defined as heroin use or prescription opioid misuse defined as: 1) use without a prescription; 2) use in greater amounts, more often, or longer than instructed; or 3) use in any other way than instructed by the prescribing clinician. | Count of Participants | Participants |
|
| OG001 | Treatment As Usual (TAU) | Participants in this arm will receive standard BUP induction protocol. TAU: 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 treatment: Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center |
|
|
|
| Secondary | 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. | Illicit opioid use is self-reported; therefore, the outcome is only reported for participants with follow-up study visits. | Posted | Mean | Standard Deviation | days | 1, 3, and 6 months |
|
|
|
| Secondary | 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. | Data was available for all participants at each time point as review was based on medical records. | Posted | Count of Participants | Participants | 1, 3, and 6 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | 3 months |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | 3 months |
|
|
|
| 0 |
| 12 |
| 8 |
| 12 |
| 12 |
| 12 |
| EG001 | Treatment As Usual (TAU) | Participants in this arm will receive standard BUP induction protocol. TAU: 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 treatment: Participants will be given an expedited appointment (within 2 weeks) to continue BUP treatment at a Montefiore community health center | 1 | 11 | 6 | 11 | 11 | 11 |
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| Overdose | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Suicidal ideation | Psychiatric disorders | Systematic Assessment | Participants endorsing, "thoughts that you would be better off dead, or of hurting yourself," as part of the 9-item Patient Health Questionnaire (PHQ-9) assessment were considered to have suicidal ideation |
|
| Asthenia | Nervous system disorders | Systematic Assessment |
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| Chills | General disorders | Systematic Assessment |
|
| Fever | General disorders | Systematic Assessment |
|
| Flu Syndrome | Infections and infestations | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Infection | Infections and infestations | Systematic Assessment |
|
| Accidental Injury | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Pain - general | General disorders | Systematic Assessment |
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| Pain - abdominal | Gastrointestinal disorders | Systematic Assessment |
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| Pain - back | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Withdrawal syndrome | General disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Acid Reflux | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Depression | Psychiatric disorders | Systematic Assessment |
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| Dizziness | General disorders | Systematic Assessment |
|
| Insomnia | General disorders | Systematic Assessment |
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| Nervousness | General disorders | Systematic Assessment |
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| Somnolence | General disorders | Systematic Assessment |
|
| Coughing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pharyngitis | Infections and infestations | Systematic Assessment |
|
| Rhinitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Sweating | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Lacrimation | Eye disorders | Systematic Assessment |
|
| Vasodilation | Vascular disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
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| D009461 |
| Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Illicit opioid use at 3 months |
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| Illicit opioid use at 6 months |
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| 6 Month |
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