Tirzepatide Combined With Cognitive-Behavioural Therapy (CBT) for Adults With Alcohol Use Disorder (AUD) and Overweight/Obesity (OOB)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Heavy Drinking Days
研究概览
简要总结
The investigators approach is to conduct a Phase II Double-Blind randomised controlled trial with individuals with co-occurring Alcohol Use Disorder and overweight/obesity (AUD-OOB) to receive either a sub-cutaneous injection of Tirzepatide (2.5 mg for 4 weeks followed by 5 mg for 4 weeks) or visually matched sham saline injection, in combination with a structured behavioural intervention (Take Control CBT Module). The primary aim of the study is evaluate the efficacy of the intervention on the number of heavy drinking days (defined as 5+ standard drinks for men, 4+ standard drinks for women) during the final month of treatment (weeks 5 to 8) compared to baseline. The secondary aim of the study is to assess treatment effects on alcohol related (e.g. number drinks consumed per day, abstinent days) and cardio-metabolic outcomes (e.g. body weight in kg, waist circumference, blood pressure, HbA1c, total cholesterol etc...), and summarise safety outcomes associated with use (e.g. frequency and severity of side effects, number of serious adverse events, treatment related discontinuations). The study will also include neurobiological assessments such as functional magnetic resonance imaging (fMRI) and lab-based psychophysiology to assess the impact of tirzepatide on change in brain activity and autonomic responses to alcohol and food cues.
详细描述
Individuals with co-occurring AUD and overweight or obesity (AUD-OOB) are an underserved population with high relapse rates and elevated cardiometabolic risk. Recent evidence suggests that Tirzepatide can simultaneously reduce alcohol intake in animal models and craving, drinks per day and heaving drinking days over a 9-week period in non-treatment seeking individuals with AUD. Tirzepatide's dual incretin mechanism offers the potential to simultaneously reduce alcohol use and improve metabolic health in this group, with a favourable safety profile and weekly dosing that supports adherence. As rates of AUD and obesity continue to rise, identifying pharmacological strategies that can address both conditions concurrently is a high public health priority.
This is a phase II, randomised, double-blind, placebo-controlled clinical trial of 46 individuals designed to evaluate the effects of Tirzepatide on alcohol consumption, craving and cardiometabolic outcomes in adults with alcohol used disorder and overweight/obesity (AUD-OOB), to receive either a sub-cutaneous injection of tirzepatide (n=23) or a visually matched placebo (n=23).
The trial will be conducted at a single clinical site in New South Wales, Australia. The Edith Collins Centre (ECC) will serve as the coordinating centre.
In summary participants will:
- Be randomized in a double-blind fashion to receive either tirzepatide or a visually matched placebo
- Receive subcutaneous injections of tirzepatide (2.5mg for 4 weeks followed by 5mg for 4 weeks) or a matching placebo over an eight-week treatment period.
- Visit the clinic weekly (for 8 weeks) for medication administration, clinical monitoring and brief behavioural support (delivered by the "Take Control" computerised CBT program).
- Receive clinical assessments including alcohol use, cardiometabolic biomarkers (HbA1c, lipids, ASCVD) and alcohol biomarkers (PEth) at baseline (week 0), end of treatment (week 9) and follow-up (week 12).
- Undergo neuroimaging (fMRI) and psychophysiology assessmenrts as a substudy at 2 timepoints: baseline (week 0) and between week 7-9. These tasks will assess neural and autonomic reactivity to alcohol and food-related cues, and will support a mechanistic understanding of tirzepatide's impact on reward sensitivity and stress responsivity-key predictors of relapse and treatment outcome
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
- Double (Participant, Investigator)
盲法说明
Randomisation will be carried out using a computer-generated list prepared by an independent biostatistician who is not involved in participant recruitment or assessment. The randomisation schedule will be securely uploaded to REDCap and accessible only to unblinded pharmacy staff responsible for study drug dispensing. Investigators enrolling participants will remain blinded and will not have access to the allocation list at any stage. Unblinding will only be permissible in the event of a medical emergency where knowledge of the participant's treatment assignment is essential to inform clinical care. Such unblinding will be conducted by the study pharmacist and must be documented and justified in the participant's trial record.
入排标准
- 年龄范围
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 21 to 75 years
- •Meet DSM-5 criteria for alcohol use disorder (AUD) with at least moderate severity (≥4 symptoms in the past year)
- •Have an average daily alcohol consumption of:
- •≥60g ethanol/day for men
- •≥40g ethanol/day for women (based on the 28 days prior to the baseline visit)
- •Body mass index (BMI) ≥27 kg/m²
- •Currently motivated to reduce or stop drinking but not engaged in formal AUD treatment
- •Able and willing to attend weekly clinic visits and complete all study procedures
- •Fluent in English and able to provide informed consent
- •Stable housing situation (not transient or homeless)
排除标准
- •Past-year DSM-5 diagnosis of another substance use disorder (except nicotine or mild cannabis use disorder)
- •Recent (past 30 days) self-reported illicit drug use (excluding cannabis), or a positive urine drug screen for non-cannabis substances
- •History of significant alcohol withdrawal, defined by:
- •History of seizure, delirium tremens, or
- •Hospitalisation for withdrawal, or
- •CIWA-Ar score >9, or
- •PAWS score >4 at screening
- •Currently engaged in pharmacological or behavioral treatment for AUD, or prior engagement within the past 3 months
- •History or current diagnosis of:
- •Type 1 or Type 2 diabetes
- •Diabetic complications (e.g. retinopathy)
- •HbA1c ≥6.5% at screening
- •Significant psychiatric illness, including:
- •Current active suicidal ideation (per C-SSRS)
- •Lifetime history of psychosis or bipolar disorder
- •Unstable depression or anxiety interfering with daily functioning
- •Chronic or acute pancreatitis
- •Significant liver disease or abnormal liver function tests (ALT, AST, ALP, bilirubin >3× ULN)
- •Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) type I/II
- •Estimated glomerular filtration rate (eGFR) <30 mL/min
- •Recent significant weight loss (>5% of body weight in past 30 days)
- •Use of any weight loss medication (e.g., orlistat, bupropion-naltrexone) or AUD medication (e.g., naltrexone, acamprosate, topiramate, varenicline) in the past 3 months
- •Use of tirzepatide or any GLP-1 receptor agonist in the past 6 months
- •Pregnant or breastfeeding, or not using effective contraception (females of childbearing potential)
- •Inability to attend weekly visits due to work/travel/schedule conflicts
- •Participation in another clinical trial involving an investigational product
- •Shared household with a current or past participant in this trial
- •Scheduled for surgery requiring anaesthesia within 90 days of enrolment that would interfere with participation or follow-up
- •History of muscle wasting, bone disorders (e.g. sarcopenia)
- •Active gastrointestinal conditions that could interfere with treatment (e.g., severe GERD)
- •Uncontrolled hypertension, recent heart attack or stroke (within 6 months)
- •Extra Exclusion criteria for Those Participants Agreeing to Participate in Neuroimaging & Psychophysiology Tasks:
- •Presence of any MRI-incompatible metal implants or devices, including pacemakers, aneurysm clips, insulin pumps, or cochlear implants
- •History of brain surgery or penetrating head trauma
- •Prior occupation as a machinist, welder, or metal worker (due to risk of metal fragments)
- •Non-removable piercings or dental hardware that would interfere with MRI
- •History of claustrophobia likely to interfere with scanning compliance aa. Neurological disorders (e.g., epilepsy, multiple sclerosis) likely to confound neuroimaging data bb. Inability to lie still or tolerate MRI procedures cc. Patient weighting over 159kg (MRI scan limit) dd. Any other condition or medication judged by the investigator to preclude safe participation
研究组 & 干预措施
Tirzepatide: subcutaneous administration of Tirzepatide plus CBT ("Take Control" program)
1 x Screening, Baseline Clinical Assessments, Neuroimaging (T0) and Psychophysiology, Randomisation (Visit 1, Week 0)
From Dose 1 (Visit 2, week 1) to Dose 4 (Visit 5, week 4), with "Take Control" CBT module: 2.5mg Tirzepatide dose administration, and a 15-20 minutes computer-based CBT module.
From Dose 5 (Visit 6 , week 5) to Dose 8 (Visit 9, week 8) with "Take Control" CBT module: 5.0mg dose administration (unless contraindicated by study physician), and a 15-20 minutes computer-based CBT module.
Neuroimaging substudy (Visit 10, week 8): After the final medication and CBT module, participants complete final neuroimaging timepoint (T1).
End-of-treatment (Visit 11, week 9 & Visit 12, week 12): One and four weeks after the last dose and neuroimaging, participants will complete psychophysiology assessments using the same tasks as baseline.
干预措施: Tirzepatide (Drug)
Tirzepatide: subcutaneous administration of Tirzepatide plus CBT ("Take Control" program)
1 x Screening, Baseline Clinical Assessments, Neuroimaging (T0) and Psychophysiology, Randomisation (Visit 1, Week 0)
From Dose 1 (Visit 2, week 1) to Dose 4 (Visit 5, week 4), with "Take Control" CBT module: 2.5mg Tirzepatide dose administration, and a 15-20 minutes computer-based CBT module.
From Dose 5 (Visit 6 , week 5) to Dose 8 (Visit 9, week 8) with "Take Control" CBT module: 5.0mg dose administration (unless contraindicated by study physician), and a 15-20 minutes computer-based CBT module.
Neuroimaging substudy (Visit 10, week 8): After the final medication and CBT module, participants complete final neuroimaging timepoint (T1).
End-of-treatment (Visit 11, week 9 & Visit 12, week 12): One and four weeks after the last dose and neuroimaging, participants will complete psychophysiology assessments using the same tasks as baseline.
干预措施: Take Control CBT Module (Behavioral)
Placebo: subcutaneous administration of placebo plus CBT ("Take Control" program)
1 x Screening, Baseline Clinical Assessments, Neuroimaging (T0) and Psychophysiology, Randomisation (Visit 1, Week 0)
From Dose 1 (Visit 2, week 1) to Dose 4 (Visit 5, week 4), with "Take Control" CBT module: matched placebo dose administration OR matched placebo, and a 15-20 minutes computer-based CBT module.
From Dose 5 (Visit 6 , week 5) to Dose 8 (Visit 9, week 8) with "Take Control" CBT module: matched placebo administration, and a 15-20 minutes computer-based CBT module.
Neuroimaging substudy (Visit 10, week 8): After the final medication and CBT module, participants complete final neuroimaging timepoint (T1).
End-of-treatment (Visit 11, week 9 & Visit 12, week 12): One and four weeks after the last dose and neuroimaging, participants will complete psychophysiology assessments using the same tasks as baseline.
干预措施: Take Control CBT Module (Behavioral)
Placebo: subcutaneous administration of placebo plus CBT ("Take Control" program)
1 x Screening, Baseline Clinical Assessments, Neuroimaging (T0) and Psychophysiology, Randomisation (Visit 1, Week 0)
From Dose 1 (Visit 2, week 1) to Dose 4 (Visit 5, week 4), with "Take Control" CBT module: matched placebo dose administration OR matched placebo, and a 15-20 minutes computer-based CBT module.
From Dose 5 (Visit 6 , week 5) to Dose 8 (Visit 9, week 8) with "Take Control" CBT module: matched placebo administration, and a 15-20 minutes computer-based CBT module.
Neuroimaging substudy (Visit 10, week 8): After the final medication and CBT module, participants complete final neuroimaging timepoint (T1).
End-of-treatment (Visit 11, week 9 & Visit 12, week 12): One and four weeks after the last dose and neuroimaging, participants will complete psychophysiology assessments using the same tasks as baseline.
干预措施: Placebo (Other)
结局指标
主要结局
Heavy Drinking Days
时间窗: 12 weeks (measured at baseline, during the final 4 weeks of treatment [weeks 5 - 8], end of treatment [week 9], and follow-up [week 12]).
Reduction in Heavy Drinking Days (HDD; defined as 4 or more drinks in a day for women and 5 or more drinks in a day for men). This will be measured by the Timeline Follow Back.
次要结局
- Proportion of participants with zero heavy drinking days(4 weeks (weeks 5 to 8))
- Number of drinks per drinking day consumed(12 weeks (weekly, from baseline visit to final follow-up visit at week 12))
- Alcohol Craving(12 weeks (weekly, from baseline visit to final follow-up visit at week 12))
- Abstinent days(12 weeks (weekly, from baseline visit to final follow-up visit at week 12))
- Waist circumference(Measured at baseline [week 0] and at end of treatment [week 9])
- Blood pressure(9 weeks (weekly, from baseline visit to final dose at week 8))
- Total cholesterol(3 weeks (Measured at baseline [week 0] and at end of treatment [week 9], and week 12 if clinically indicated))
- Changes in Positive and Negative Mood States(Week 1 (prior to dose 1) and at EOT (end of treatment/week 8))
- Alcohol craving measure 2(12 weeks - measured weekly from baseline (week 1) to outcomes/discharge (week 12))
- WHO drinking risk level scale.(12 weeks (weekly, from baseline visit to final follow-up visit at week 12))
- Body weight(Measured at baseline [week 0] and at end of treatment [week 9].)
- 10-year ASCVD risk score(Measured at baseline [week 0] and end of treatment [week 9].)
- HbA1c(3 weeks (Measured at baseline [week 0] and at end of treatment [week 9], and week 12 if clinically indicated))
- Frequency and severity of side effects/adverse events (AEs)(12 weeks (at each visit))
- Number of treatment-related discontinuation(12 weeks (at each visit))
- Triglycerides(3 weeks (Measured at baseline [week 0] and at end of treatment [week 9], and week 12 if clinically indicated))
研究者
Kirsten Morley BPsych MPH PhD
Professor
South West Sydney Local Health District