Brigham Research Institute (BRI) - Brigham and Women's Hospital

Oral Buprenorphine as a Novel Low-dose Induction Strategy for Opioid Use Disorder

Purpose

This is a human laboratory-based, randomized, cross-over study in which buprenorphine will be administered to healthy volunteers (n=22) in 3 separate inpatient 2-night visits, at least 1 week apart. At each visit, the participant will receive a single dose buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO. Participants will be given naltrexone to produce opioid blockade to eliminate the risk for opioid dependence in individuals without OUD. Timed blood samples will be collected up to 24 hours.

Condition

Opioid Use Disorder

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: Yes

Inclusion Criteria

English-speaking adults aged 18 and above. - In good physical health as determined by routine medical screening consisting of a complete physical exam, safety labs and EKG. - Baseline vital signs with HR between 60 and 100, SBP between 90 and 160mmHg, and respiratory rate between 12 and 20 breaths per minute. - Prior personal history of opioid use, therapeutic or non-therapeutic in past the 12 months.

Exclusion Criteria

DSM-5 diagnosis of any substance use disorder excluding tobacco. - Presence of any alcohol, cannabis, opioids (including methadone, buprenorphine) or any other illicit substances on urine toxicology at any study visit, including cocaine, amphetamines, and benzodiazepines. - Receiving treatment with opioid analgesic in last 60 days, or anticipate requiring opioids during the proposed trial, or up to 30 days after the trial completion - Baseline PHQ-9 or GAD7 > 10 (i.e. moderate depression/anxiety) - History of chronic pain - Psychotic disorder, active suicidality or homicidally, or any psychiatric condition that impair ability to provide informed consent. - History of hypersensitivity or allergy to buprenorphine or naltrexone - Pregnant or breastfeeding. - Liver function test greater than 3 times upper normal limit. - Receiving medications that are strong or moderate CYP34A inducers or inhibitors (including but not limited to ketoconazole, itraconazole, clarithromycin, fluconazole, erythromycin), in the past 30 days.

Study Design

Phase: Phase 1
Study Type: Interventional
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: All participants will first receive the IV arm in fixed order, in an open-label fashion. Subsequently, participants will be randomized to the two PO.
Primary Purpose: Other
Masking: None (Open Label)
Masking Description: All portions will be open label

Arm Groups

Arm	Description	Assigned Intervention
Experimental 8mg PO buprenorphine	After the open-label period, the participant will receive 8mg PO, then 16mg PO will be administered in the following visit.	Drug: Buprenorphine At each visit, the participant will receive a single dose of buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO.
Experimental 16mg PO buprenorphine	After the open-label period, the participant will receive 16mg PO, then 8mg PO will be administered in the following visit.	Drug: Buprenorphine At each visit, the participant will receive a single dose of buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO.
Experimental 0.15mg IV Dose	The first dose administered will be fixed to an open-label 0.15mg IV dose.	Drug: Buprenorphine At each visit, the participant will receive a single dose of buprenorphine, either 0.15mg IV, 8mg PO, or 16mg PO. The order for the first dose administered will be fixed to the IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO.

Recruiting Locations

Brigham and Women's hospital
Boston 4930956, Massachusetts 6254926 02115

More Details

Status: Recruiting
Sponsor: Brigham and Women's Hospital

Study Contact

Joji Suzuki, MD
6177325752
jsuzuki2@bwh.harvard.edu

Detailed Description

The approach is to conduct a randomized, cross-over trial in a controlled human laboratory setting with healthy volunteers (n=22). After obtaining informed consent, eligible participants will be scheduled for 3 separate two-night test days to receive 0.15mg IV, 8mg PO, or 16mg PO of buprenorphine. The first dose administered will be fixed to an open-label IV dose, and the subsequent doses will be randomized and counterbalanced to 8mg or 16mg PO. Visits will be scheduled at least 1 week apart to allow for washout of drug. One hour prior to receipt of the buprenorphine dose, all participants will be fed a standardized light breakfast. The IV dose will be given after establishing IV access, while the PO doses will be swallowed whole. Participants will also receive oral naltrexone 100mg 24 hours prior to each dosing to provide blockade at the mu-receptor, as well as 50mg PO at the study visit itself prior to receipt of buprenorphine. Timed blood samples will be collected in heparinized Vacutainer tubes via a catheter in the antecubital vein at baseline, and at 0.5, 1, 2, 4, 8, and 24 hours. Samples will be centrifuged and frozen until analysis.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.