Semaglutide for Helping Opioid Recovery

Phase 2RecruitingNCT06639464

Brigham and Women's Hospital46 enrolled

Overview

The is a pilot, 12-week, double-blind, placebo-controlled, randomized trial of individuals with opioid use disorder (OUD) newly initiating buprenorphine to receive either weekly injections of semaglutide (n=23) or matching placebo (n=23). The primary aim is to determine the effects of semaglutide on cue-reactivity among individuals with OUD. The secondary aim is to assess the preliminary efficacy, safety, and tolerability of semaglutide for OUD.

Participants include N=46 men and women with DSM5 diagnosis of OUD who are newly initiating sublingual buprenorphine (SL-BUP), defined as within 60 days of enrollment. Only those participants who have attained stable SL-BUP dosing (i.e. no change in dose) for at least 30 days prior to enrollment and plan to remain on the SL-BUP for the duration of the trial will be eligible. Potential participants will be screened and enrolled only if they meet full inclusion criteria. After baseline procedures are complete, participants will be randomized to semaglutide or placebo. Following randomization, participants will be scheduled for thirteen weekly study visits. Each visit will last approximately 1 hour, except for study visits 1 (baseline), 7, and 14 (follow-up) which will take no more than 3 hours in order to conduct reward- and stress-related neurocognitive testing. At each visit, participants will complete vital signs, weight, urine toxicology testing, and a blood testing for glucose. Participants will also complete an assessment of adverse events and questionnaires probing secondary outcomes (i.e. anxiety and depression, suicidality, substance use, opioid withdrawal symptoms, craving questionnaire). Blood samples will be collected at the beginning, middle, and end of the study. At study visits 2-13, the weekly dose of semaglutide or placebo will be administered. Both participants and study staff (including raters) will be blinded to active drug vs. placebo. The medication will be purchased from the manufacturer, and stored in the BWH Investigational Drug Service (IDS). The IDS will then extract the semaglutide and draw the dose into syringes, which will be matching visually with the placebo doses.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Opioid Use Disorder

Interventions

SemaglutideDRUG

This intervention will consist of the FDA-approved dosing schedule, with terminal dosage based on manufacturer's recommendation to titrate to 1mg over 12 weeks. Participants will receive 0.25mg for the first 4 weeks, 0.5mg for the next 4 weeks, and 1.0mg for the final 4 weeks. IDS will extract semaglutide an draw the doses into syringes for matching placebo doses to also be produced and maintain blind.

PlaceboOTHER

Placebo syringes of saline and matching volume will be produced by IDS.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * English speaking adults aged 18 and above * DSM-5 diagnosis of opioid use disorder, severe * Initiated sublingual buprenorphine (SL-BUP) treatment within 60 days of enrollment * Attained stable dosing of SL-BUP of 16mg or greater for 30 days prior to enrollment * Anticipating continuation of SL-BUP for the duration of the trial * Agreeable with bringing SL-BUP prescription to visits to allow study team to conduct a dose count * Willing to grant study team permission to communicate about SL-BUP treatment with community prescriber via completion of 42 CFR release Individuals with any of the following will be excluded: * DSM-5 diagnosis of any current substance use disorder excluding opioid, cannabis or tobacco * Active psychosis, active suicidality or homicidality or any psychiatric condition that impair ability to provide informed consent * Any current or lifetime diagnosis of eating disorders * BMI\<25mg/kg2 * Current or lifetime diagnosis of Type 1 or Type 2 diabetes * Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 * Use of any GLP-1 agonist medications in the prior 3 months * Anticipating receipt of any GLP-1 agonist medications during the trial * History of angina pectoris, coronary heart disease, congestive heart failure, inflammatory bowel disease, chronic obstructive pulmonary disease, bariatric surgery, idiopathic pancreatitis, diabetic gastroparesis * Liver function test greater than 3 times upper normal limit * Renal impairment as indicated by eGFR of \<60 * History of hypersensitivity or allergy to semaglutide * Pregnant or breastfeeding * Anticipated to participate in a concurrent drug trial * Any other reason or clinical condition that the investigators judge may interfere with study participation and/or be unsafe for a participant

Locations (1)

Brigham and Women's Hospital

Boston, Massachusetts, United States

RECRUITING

Outcomes

Primary Outcomes

Cue-induced Cravings for Opioids

Cue-induced craving scores at study completion compared to baseline using a standard cue-reactivity paradigm utilizing visual cues. Cravings will be measured on a scale from 0-10 with 10 meaning extreme cravings.

Time frame: Baseline, 6 weeks, and 13 weeks after baseline visit

Relapse to Illicit Opioid Use

the primary outcome is proportion of participants who relapse to illicit opioids use at study completion, defined as the start of 4 consecutive opioid "use weeks" or at the start of 7 consecutive days of self-reported opioid use days. A "use week" is defined as any week in which participants self-report at least one day of illicit opioid use, provide a urine test positive for illicit opioids, or fail to provide a urine sample for testing. The study investigators will use Time-Line Follow Back (TLFB), a gold-standard method of evaluating substance use, as well as weekly urine toxicology screens.

Time frame: Weekly from baseline to end of study at 14 weeks

Secondary Outcomes

Visual Probe Task

A behavioral task to assess attentional bias. Opioid-related and neutral images will be used, different from the ones used for the cue-reactivity paradigm to limit habituation. A pair of images will appear on the left and right of the screen for either a short (200ms) or long (500ms) stimulus duration to assess automatic orientating and controlled attention processing, respectively. Image pairs will be replaced by a probe in the location of either the opioid-related or neutral image. The probe will remain until the participant responds to identify the probe orientation by pressing the response keys as quickly as possible. This task will yield reaction times for analysis.

Time frame: Baseline, 6 weeks, and 13 weeks after baseline visit

Iowa Gambling Task (IGT)

A computerized task to measure risky decision making using four decks of cards (A, B, C, D). Participants are instructed to maximize profits. Cards from decks A and B earn more profits but lead to even higher occasional losses leading to net long-term losses, while decks C and D yield low profits but only low occasional losses resulting in a net long-term profit. The task will yield scores which are the sums of cards selected from decks A/B and decks C/D.

Central Contacts

Joji Suzuki

CONTACT

617-732-5752 jsuzuki2@bwh.harvard.edu

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.