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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Semaglutide | Experimental | This arm will receive semaglutide (n=23). All participants will initially receive 0.25mg for 4 weeks, and then as tolerated dose will be increased to 0.5mg for 4 weeks. Then as tolerated, the dose will be increased to 1.0mg for 4 weeks. |
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| Placebo | Placebo Comparator | This arm will receive saline placebo (n=23). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Semaglutide | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Weekly from baseline to end of study at 14 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Individuals with any of the following will be excluded:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Joji Suzuki | Contact | 617-732-5752 | jsuzuki2@bwh.harvard.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Recruiting | Boston | Massachusetts | 02115 | United States |
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| ID | Term |
|---|---|
| D009293 | Opioid-Related Disorders |
| ID | Term |
|---|---|
| D000079524 | Narcotic-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C000591245 | semaglutide |
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The IDS will perform both the randomization and blinding, and will be the only research staff that will remain unblinded. The IDS will extract the semaglutide and draw the dose into syringes, which will be made to match visually with the placebo saline doses. All other research staff will remain blinded for the duration of the trial.
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| Placebo | Other | Placebo syringes of saline and matching volume will be produced by IDS. |
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| 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. | Baseline, 6 weeks, and 13 weeks after baseline visit |
| Monetary Choice Questionnaire (MCQ) | A self-report tool used to measure delayed discounting. Participants will be asked to pick one of the two choices given. Score calculated typically falls between 0.0 and 0.5, with smaller values indicating a lack of discounting and preference for delayed rewards and higher values indicating strong discounting and a preference for immediate rewards. | Baseline, 6 weeks, and 13 weeks after baseline visit |
| Clinical Opiate Withdrawal Scale (COWS) | Tool for assessing opioid withdrawal. Scale of 0-48, with a higher number meaning more severe withdrawal. | Weekly from baseline to end of study at 14 weeks |
| Patient Health Questionnaire (PHQ8) | A tool to assess depression symptoms. Scale of 0-24, with a higher score meaning more depression symptoms. | Weekly from baseline to end of study at 14 weeks |
| Generalized Anxiety Disorder (GAD7) | A standard tool to assess anxiety symptoms. Scale of 0-21 with a higher number indicating more anxiety. | Weekly from baseline to end of study at 14 weeks |
| WHO Quality of Life (WHOQOL-BREF) | A 26-item quality of life scale. Split into 5 domain scores: Overall Quality of Life and General Health (2-10), Physical Health (7-35), Psychological (6-30), Social relationships (3-15), and Environment (8-40). Higher scores indicate a higher quality of life. | Baseline and 13 weeks after baseline visit |
| Patient Rated Inventory of Side Effects (PRISE) | A self-report tool to qualify side effects. For each domain, the patient rates whether the symptoms are tolerable or distressing. | Weekly from 2 weeks after baseline to end of study at 14 weeks |
| Hemoglobin A1c | Hemoglobin A1c levels will be obtained via blood draw | At baseline and 13 weeks after baseline visit |
| Stanford Efficacy of treatment Scale (SETS) | An instrument for measuring patient outcome expectancy in clinical trials. Assesses positive and negative treatment expectations with 3 items each on 7-point Likert-scales from 0 'not agree at all' to 6 'fully agree'. | Baseline |
| Columbia suicide severity rating scale (C-SSRS) | A commonly used tool to assess suicidal ideation. The sum ranges from 2 to 25, with the higher number indicating more intense ideation. | Weekly from baseline to end of study at 14 weeks |
| Heart Rate | Heart rate measured in beats per minute (bpm). | Weekly from baseline to end of study at 14 weeks |
| Opioid Craving Scale | 3-item measure of craving for opioids. Each item will be measured on a scale from 0-10 with 10 meaning stronger cravings. | Weekly from baseline to end of study at 14 weeks |
| Blood pressure | Blood pressure measured as (systolic)/(diastolic). | Weekly from baseline to end of study at 14 weeks |
| Blood sugar | Blood glucose | Weekly from baseline to end of study at 14 weeks |
| Assessment of blind | Measure of participant perception of whether they received the active study drug. | 6 weeks and 13 weeks after baseline visit. |
| Height | Height measured in meters. | Weekly from baseline to end of study at 14 weeks |
| Weight | Weight measured in kilograms. | Weekly from baseline to end of study at 14 weeks |
| Temporal Experience of Pleasure Scale (TEPS) | A tool to assess both anticipatory and consummatory reward. 18-item tool where each item is ranked from 1 ('very false for me') to 6 ('very true for me'). Items are averaged, with higher score indicate a stronger tendency to anticipate or experience pleasure. | At baseline and 13 weeks after baseline visit |