Opening soonPhase 2Interventional
What this study is about
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.
A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.
Basic eligibility
Age21 Years to 75 Years
SexAll
Healthy volunteersNot accepted
ConditionAlcohol Use Disorder (AUD), Overweight or Obese, Comorbidities and Coexisting Conditions
Full registry criteria
Inclusion Criteria: 1. Aged 21 to 75 years 2. Meet DSM-5 criteria for alcohol use disorder (AUD) with at least moderate severity (≥4 symptoms in the past year) 3. 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) 4. Body mass index (BMI) ≥27 kg/m² 5. Currently motivated to reduce or stop drinking but not engaged in formal AUD treatment 6. Able and willing to attend weekly clinic visits and complete all study procedures 7. Fluent in English and able to provide informed consent 8. Stable housing situation (not transient or homeless) Exclusion Criteria: 1. Past-year DSM-5 diagnosis of another substance use disorder (except nicotine or mild cannabis use disorder) 2. Recent (past 30 days) self-reported illicit drug use (excluding cannabis), or a positive urine drug screen for non-cannabis substances 3. 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 4. Currently engaged in pharmacological or behavioral treatment for AUD, or prior engagement within the past 3 months 5. History or current diagnosis of: * Type 1 or Type 2 diabetes * Diabetic complications (e.g. retinopathy) * HbA1c ≥6.5% at screening 6. 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 7. Chronic or acute pancreatitis 8. Significant liver disease or abnormal liver function tests (ALT, AST, ALP, bilirubin \>3× ULN) 9. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) type I/II 10. Estimated glomerular filtration rate (eGFR) \<30 mL/min 11. Recent significant weight loss (\>5% of body weight in past 30 days) 12. 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 13. Use of tirzepatide or any GLP-1 receptor agonist in the past 6 months 14. Pregnant or breastfeeding, or not using effective contraception (females of childbearing potential) 15. Inability to attend weekly visits due to work/travel/schedule conflicts 16. Participation in another clinical trial involving an investigational product 17. Shared household with a current or past participant in this trial 18. Scheduled for surgery requiring anaesthesia within 90 days of enrolment that would interfere with participation or follow-up 19. History of muscle wasting, bone disorders (e.g. sarcopenia) 20. Active gastrointestinal conditions that could interfere with treatment (e.g., severe GERD) 21. Uncontrolled hypertension, recent heart attack or stroke (within 6 months) Extra Exclusion criteria for Those Participants Agreeing to Participate in Neuroimaging \& Psychophysiology Tasks: 22. Presence of any MRI-incompatible metal implants or devices, including pacemakers, aneurysm clips, insulin pumps, or cochlear implants 23. History of brain surgery or penetrating head trauma 24. Prior occupation as a machinist, welder, or metal worker (due to risk of metal fragments) 25. Non-removable piercings or dental hardware that would interfere with MRI 26. 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
Treatments and study arms
Tirzepatide
Drug
Subcutaneous injection once weekly for 8 weeks: 2.5 mg/week initially for Weeks 1-4, then 5.0 mg/week for Weeks 5-8 (Dose escalation from 2.5 mg to 5.0 mg will occur at Week 5 unless the study physician advises continuation at the lower dose due to tolerability concerns. Delays or dose adjustments will be made per the physician's clinical judgment).
Take Control CBT Module
Behavioral
The Take Control intervention is a structured CBT intervention or manualised digital therapy designed to support alcohol reduction. Take Control will be completed using a computer interface with headphones in a private room. Participants will complete one module per week during treatment Weeks 1 to 8. Each module is approximately 30-45 minutes in length and will be completed independently by the participant under the supervision of a research assistant. Program content is fixed and self-paced, eliminating the need for fidelity monitoring of therapist behaviour. Take Control is an evidence-informed cognitive-behavioural intervention originally developed for use in pharmacotherapy trials for AUD and has demonstrated feasibility and acceptability in similar populations. The intervention content draws on established CBT strategies for alcohol reduction, including motivational enhancement, managing triggers, coping skills, and relapse prevention.
Placebo
Other
Participants in the placebo condition will receive visually-matched sham injections, where by the placebo container and contents will be identical in appearance to Tirzepatide, except without the active ingrediant.
