Semaglutide for the Treatment of Opioid Use Disorder: A Pilot Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Cue-induced Cravings for Opioids
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
研究组 & 干预措施
Semaglutide
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.
干预措施: Semaglutide (Drug)
Placebo
This arm will receive saline placebo (n=23).
干预措施: Placebo (Other)
结局指标
主要结局
Cue-induced Cravings for Opioids
时间窗: Baseline, 6 weeks, and 13 weeks after baseline visit
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.
Relapse to Illicit Opioid Use
时间窗: Weekly from baseline to end of study at 14 weeks
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.
次要结局
- Visual Probe Task(Baseline, 6 weeks, and 13 weeks after baseline visit)
- Iowa Gambling Task (IGT)(Baseline, 6 weeks, and 13 weeks after baseline visit)
- Monetary Choice Questionnaire (MCQ)(Baseline, 6 weeks, and 13 weeks after baseline visit)
- Clinical Opiate Withdrawal Scale (COWS)(Weekly from baseline to end of study at 14 weeks)
- WHO Quality of Life (WHOQOL-BREF)(Baseline and 13 weeks after baseline visit)
- Patient Rated Inventory of Side Effects (PRISE)(Weekly from 2 weeks after baseline to end of study at 14 weeks)
- Patient Health Questionnaire (PHQ8)(Weekly from baseline to end of study at 14 weeks)
- Blood pressure(Weekly from baseline to end of study at 14 weeks)
- Blood sugar(Weekly from baseline to end of study at 14 weeks)
- Generalized Anxiety Disorder (GAD7)(Weekly from baseline to end of study at 14 weeks)
- Hemoglobin A1c(At baseline and 13 weeks after baseline visit)
- Stanford Efficacy of treatment Scale (SETS)(Baseline)
- Columbia suicide severity rating scale (C-SSRS)(Weekly from baseline to end of study at 14 weeks)
- Heart Rate(Weekly from baseline to end of study at 14 weeks)
- Opioid Craving Scale(Weekly from baseline to end of study at 14 weeks)
- Assessment of blind(6 weeks and 13 weeks after baseline visit.)
- Height(Weekly from baseline to end of study at 14 weeks)
- Weight(Weekly from baseline to end of study at 14 weeks)
- Temporal Experience of Pleasure Scale (TEPS)(At baseline and 13 weeks after baseline visit)
研究者
Joji Suzuki, MD
Director, Division of Addiction Psychiatry
Brigham and Women's Hospital