Tirzepatide for the Treatment of Alcohol Use Disorder: A Pilot Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 3
- 主要终点
- Cue-induced Cravings for Alcohol
研究概览
简要总结
This is a pilot, 4-week, double-blind, placebo-controlled, randomized trial of individuals with alcohol use disorder (AUD) to receive weekly injections of either tirzepatide (n=10) or matching placebo (n=10). The primary aim is to determine the effects of tirzepatide on cue-reactivity among individuals with AUD. The secondary aim is to assess the safety and preliminary efficacy of tirzepatide for AUD.
详细描述
Participants include N=20 men and women with DSM5 diagnosis of AUD. Potential participants will be screened and enrolled only if they meet full inclusion criteria. After screening and baseline procedures (Visit 1) are complete, participants will be randomized to receive either tirzepatide or placebo. Following randomization, participants will be scheduled for five study visits (Visits 2-6). Each visit will last approximately 1 hour, except for study visits 1 and 6 which will take no more than 3 hours in order to conduct additional neurocognitive testing, including cue-induced cravings and decision-making tests. At all study visits, participants will complete vital signs, weight, urine toxicology testing, a blood draw for glucose, and questionnaires probing secondary outcomes (i.e. anxiety and depression, suicidality, substance use, opioid withdrawal symptoms, cravings, etc). At study visits 2-5, the weekly dose of tirzepatide or placebo will be administered, and assessment of adverse events will also be completed. Both participants and study staff (including raters) will be blinded to active drug vs. placebo. At visit 1, subjects' expectations about their potential treatment will be queried. The final visit, visit 6, also called the follow-up visit, will also assess subjects' guess as to which treatment they received. The medication will be purchased from the manufacturer and stored by IDS. The IDS will extract the tirzepatide and draw the dose into syringes, which will match 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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The IDS will perform both the randomization and blinding and will be the only unblinded research staff. They will extract the tirzepatide and draw the dose into syringes, which will match visually with the placebo 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
- •Diagnosed with current DSM-5 alcohol use disorder
- •Willing and able to physically travel to BWH CCI outpatient facilities for study visits
排除标准
- •CIWA score at screening ≥
- •Psychotic disorder, active suicidality or homicidality or any psychiatric condition that impair ability to provide informed consent
- •Any lifetime diagnosis of eating disorders including anorexia, bulimia, binge eating, or avoidant/restrictive food intake disorder
- •BMI<23 mg/kg2
- •Current or lifetime diagnosis of Type 1 or Type 2 diabetes
- •Current (or within 30 days of enrollment) use of any anti-obesity medications or medications with glucose lowering properties (including GLP-1 analogues, sulfonylurea, insulin, metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, or sodium-glucose cotransporter-2 (SGLT-2) inhibitors)
- •Use of any GLP-1 agonist medications in the prior 3 months
- •Anticipating receipt of any other GLP-1 agonist medications during the trial
- •Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
- •Current hypoglycemia as indicated by a blood sugar level of ≤70 mg/dL measured at the baseline visit
- •Calcitonin ≥ 50 ng/L
- •Triglycerides ≥500 mg/dL
- •Untreated cholelithiasis or gallbladder disease
- •Acute myocardial infarction, cerebrovascular accident (stroke), unstable angina, or congestive heart failure in the last 90 days
- •Uncontrolled hypertension at baseline, as indicated by an average blood pressure reading of >180/110 after three successive readings
- •History of inflammatory bowel disease, bariatric surgery, pancreatitis, diabetic gastroparesis, or non-arteritic anterior ischemic optic neuropathy
- •Liver function test greater than 5 times upper normal limit
- •Renal impairment as indicated by eGFR of <30
- •History of hypersensitivity or allergy to tirzepatide
- •Pregnant or breastfeeding
- •Anticipated to be enrolled in another clinical drug trial during participation in this trial
- •Any other reason or clinical condition that the investigators judge may interfere with study participation and/or be unsafe for a participant
研究组 & 干预措施
Saline Placebo
This arm will receive saline placebo injections (n=10) weekly for 4 weeks.
干预措施: Saline Placebo (Other)
Tirzepatide
This arm will receive tirzepatide (n=10) weekly 2.5mg injections for 4 weeks.
干预措施: Tirzepatide (Drug)
结局指标
主要结局
Cue-induced Cravings for Alcohol
时间窗: Baseline visit and 5 weeks after baseline visit.
Cue-induced craving scores at follow-up 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.
Cue-induced Cravings for Alcohol
时间窗: Baseline visit and 5 weeks after baseline visit.
Cue-induced craving scores at follow-up 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.
Incidence and Severity of Adverse Events
时间窗: Epic monitoring throughout the trial and PRISE administered at study weeks 2-5 (visits 3-6).
Study staff will be notified of any hospital admissions via Epic, and adverse events will be queried specifically using the Patient Rated Inventory of Side Effects (PRISE) at study weeks 2-5. The PRISE is a self-report tool to qualify side effects. For each domain, the patient indicates whether they have experienced certain symptoms and whether the symptoms are tolerable or distressing.
次要结局
- Blood Sugar(At each study visit up to and including the final visit 5 weeks after baseline.)
- Hemoglobin A1c(Baseline and 5 weeks after baseline visit.)
- Weight(At each study visit up to and including the final visit 5 weeks after baseline.)
- Heart rate(At each study visit up to and including the final visit 5 weeks after baseline.)
- Blood pressure(At each study visit up to and including the final visit 5 weeks after baseline.)
- Assessment of Blind(5 weeks after baseline visit.)
- Stanford Efficacy of Treatment Scale (SETS)(Baseline visit.)
- Monetary Choice Questionnaire (MCQ)(Baseline visit and 5 weeks after baseline visit.)
- Visual Probe Task(Baseline visit and 5 weeks after baseline visit.)
- Clinical Institute Withdrawal Assessment (CIWA)(At each study visit up to and including the final visit 5 weeks after baseline.)
- Penn Alcohol Craving Scale (PACS)(At each study visit up to and including the final visit 5 weeks after baseline.)
- Monetary Choice Questionnaire (MCQ)(Baseline visit and 5 weeks after baseline visit.)
- Visual Probe Task(Baseline visit and 5 weeks after baseline visit.)
- Percent days abstinent(At each study visit up to and including the final visit 5 weeks after baseline.)
- Percent heavy drinking days(At each study visit up to and including the final visit 5 weeks after baseline.)
- Drinks per drinking day(At each study visit up to and including the final visit 5 weeks after baseline.)
- Clinical Institute Withdrawal Assessment (CIWA)(At each study visit up to and including the final visit 5 weeks after baseline.)
- Blood Sugar(At each study visit up to and including the final visit 5 weeks after baseline.)
- Hemoglobin A1c(Baseline and 5 weeks after baseline visit.)
- Weight(At each study visit up to and including the final visit 5 weeks after baseline.)
- Columbia Suicide Severity Rating Scale (C-SSRS)(At each study visit up to and including the final visit 5 weeks after baseline.)
- Patient Health Questionnaire-8 (PHQ-8)(At each study visit up to and including the final visit 5 weeks after baseline.)
- Generalized Anxiety Disorder-7 (GAD-7)(At each study visit up to and including the final visit 5 weeks after baseline.)
- Heart rate(At each study visit up to and including the final visit 5 weeks after baseline.)
- Blood pressure(At each study visit up to and including the final visit 5 weeks after baseline.)
- Assessment of Blind(5 weeks after baseline visit.)
- Stanford Efficacy of Treatment Scale (SETS)(Baseline visit.)
- Fibrosis-4 (FIB-4)(Baseline visit and 5 weeks after baseline visit.)
研究者
Joji Suzuki, MD
Director, Division of Addiction Psychiatry
Brigham and Women's Hospital