Alcohol Use Disorder (AUD)Phase 2NCT07292519
Tirzepatide Combined With Cognitive-Behavioural Therapy (CBT) for Adults With Alcohol Use Disorder (AUD) and Overweight/Obesity (OOB)
A Phase 2 study testing Tirzepatide in people with Alcohol Use Disorder (AUD) and Overweight or Obese, run by South West Sydney Local Health District at 1 site in Australia.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Alcohol Use Disorder (AUD), Overweight or Obese, Comorbidities and Coexisting Conditions
- What is being tested?
- Tirzepatide
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteAustralia
- Study dates
- 15 Jan 2026to 15 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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)
Who cannot join
- 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
Show all 37Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site
Drug Health Services, Royal Prince Alfred Hospital
Sydney, New South Wales, 2050
Kirsten C Morley, PhD, Kirsten.morley@sydney.edu.au
Central Contact Line, 0459877108
About this study
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.
Read the detailed description
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
The primary aim of this clinical trial is to examine the effects of weekly tirzepatide (2.5 mg for 4 weeks followed by 5 mg for 4 weeks) versus placebo injections, in combination with a structured behavioural intervention (Take Control) on alcohol consumption in adults with alcohol use disorder and overweight/obesity (AUD-OOB). The main question[s] it aims to answer are:
- Main outcome: To determine the efficacy of Tirzepatide on alcohol related outcomes, the change in the number of heavy drinking days during the final four weeks of treatment (week 5 - 8, with a final assessment at week 9) will be assessed by comparison with baseline (28 days prior to baseline visit). Researchers will compare tirzepatide to placebo injections (a look-alike substance that contains no drug) to see if weekly tirzepatide administration can reduce the number of heavy drinking days.
- Secondary Outcomes:
- To evaluate changes in additional alcohol-related outcomes:
- Number of drinks per drinking day measured using the Timeline Follow Back
- Number of abstinent days measured using the Timeline Follow Back
- WHO drinking risk level
- Weekly alcohol craving
- Proportion of participants with zero heavy drinking days (Weeks 5-8) ii) To evaluate changes in cardiometabolic indices from baseline to Week 9:
- Body weight
- Waist circumference
- Blood pressure
- HbA1c
- Total cholesterol
- Triglycerides
- 10-year ASCVD risk score iii) To assess safety outcomes associated the delivery of Tirzepatide, investigators will measure the:
- Frequency and severity of side effects (graded using CTCAE V5.0 and monitored continuously throughout the intervention).
- Number of serious adverse events (SAEs)
- Treatment-related discontinuation Participants will complete additional neurobiological assessments including functional magnetic resonance imaging (fMRI) and laboratory-based psychophysiology at two timepoints: baseline (pre-treatment) and the final treatment visit (Week 8), which coincides with the final tirzepatide/placebo dose and final Take Control session. These measures will assess changes in brain activity and autonomic responses to alcohol and food cues.
- Being tested
- Tirzepatide, Take Control CBT Module, Placebo
- Keywords
- Alcohol Use Disorder (AUD), Overweight or Obese, Concurrent Treatment of AUD and overweight/obesity, Tirzepatide, Phase II Double-blind RCT
- Medical subject headings
- Alcoholism, Overweight, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Also called GLP-1/GIP receptor dual agonist
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 ModuleBehavioural
Also called Take Control Cognitive Behavioural Therapy Module
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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Tirzepatide: subcutaneous administration of Tirzepatide plus CBT ("Take Control" program) | Experimental | 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. Receives: Drug: Tirzepatide; Behavioral: Take Control CBT Module |
| Placebo: subcutaneous administration of placebo plus CBT ("Take Control" program) | Placebo comparator | 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. Receives: Behavioral: Take Control CBT Module; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heavy Drinking Days
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.
Measured: 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]).
Secondary outcomes (16)
Number of drinks per drinking day consumed
Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels
Measured: 12 weeks (weekly, from baseline visit to final follow-up visit at week 12)
Abstinent days
Measured by Timeline Follow Back
Measured: 12 weeks (weekly, from baseline visit to final follow-up visit at week 12)
Alcohol Craving
As measured the Visual Analogue Scale (VAS) weekly and also at pre-, during-, and post- psychophysiological cue-reactivity task completion. Scored from to 0 to 100, where higher scores indicate more severe craving.
Measured: 12 weeks (weekly, from baseline visit to final follow-up visit at week 12)
WHO drinking risk level scale.
The WHO drinking risk level scale categorizes alcohol consumption based on average daily intake of pure alcohol (in grams) and its associated health risk.
There are 5 levels that differ based on gender:
- For men, very high risk >100 grams/day or; high risk as >60 to 100 grams/day ; moderate risk as >40 to 60 grams/day; and low risk as 1 to 40 grams/day.
- For women, very high risk was defined as >60 grams/day; high risk as >40 to 60 grams/day; moderate risk as >20 to 40 grams/day ; and low risk as 1 to 20 grams/day.
Measured: 12 weeks (weekly, from baseline visit to final follow-up visit at week 12)
Proportion of participants with zero heavy drinking days
Proportion of participants with zero heavy drinking days measured by the TLFB.
Measured: 4 weeks (weeks 5 to 8)
Body weight
Changes in body weight in kilograms (kg) from baseline to week 9 (end of treatment).
Measured: Measured at baseline [week 0] and at end of treatment [week 9].
Waist circumference
Changes in waist circumference in centimetres (cm) from baseline to week 9 (end of treatment).
Measured: Measured at baseline [week 0] and at end of treatment [week 9]
Blood pressure
Systolic and diastolic blood pressure measured weekly from baseline to end of treatment (week 8).
Measured: 9 weeks (weekly, from baseline visit to final dose at week 8)
HbA1c
Clinical metabolic monitoring for cardiometabolic risk and drug safety. Measures glycated haemoglobin in a blood in percentages (%). Collected at screening (Week 0) and again at the end-of-treatment visit (Week 9). Additional testing may be conducted at follow up (week 12) if clinically indicated.
Measured: 3 weeks (Measured at baseline [week 0] and at end of treatment [week 9], and week 12 if clinically indicated)
10-year ASCVD risk score
A cardiometabolic biomarker providing an estimation of 10-year atherosclerotic cardiovascular disease (ASCVD) risk score, based on pooled cohort equations. This is a composite risk score derived from traditional cardiovascular risk factors, including gender, age, race, total cholesterol, total HDL cholesterol, systolic BP, previous receipt of treatment for high blood pressure (if SBP > 120 mmHg), diabetes and smoking status.
This is used to provide a risk score of atherosclerotic cardiovascular disease.
Measured: Measured at baseline [week 0] and end of treatment [week 9].
Frequency and severity of side effects/adverse events (AEs)
Safety outcomes including adverse events (AEs), serious adverse events (SAEs), and vital sign abnormalities, will be summarised descriptively across the study period. Feasibility outcomes (e.g., recruitment and retention rates, session attendance) will be analysed using proportions with corresponding 95% confidence intervals.
Measured: 12 weeks (at each visit)
Number of treatment-related discontinuation
As a measure of safety, the number of treatment-related discontinuations will be measured.
Measured: 12 weeks (at each visit)
Total cholesterol
Clinical metabolic monitoring for total cholesterol in millimoles per litre (mmol/L). Collected at screening (Week 0) and again at the end-of-treatment visit (Week 9). Additional testing may be conducted at follow up (week 12) if clinically indicated.
Measured: 3 weeks (Measured at baseline [week 0] and at end of treatment [week 9], and week 12 if clinically indicated)
Triglycerides
Clinical metabolic monitoring for triglycerides in blood sample, measured via millimoles per litre (mmol/L) as a measure of cardiometabolic risk and drug safety. Collected at screening (Week 0) and again at the end-of-treatment visit (Week 9). Additional testing may be conducted at follow up (week 12) if clinically indicated.
Measured: 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
Mood states before/after ketamine sessions assessed by PANAS (Positive and Negative Affect Schedule). This will be measured during neuroimaging and psychophysiology sessions. Used to measure an individual's emotional state, assessing two dimensions: Positive Affect (PA; captures feelings like enthusiasm and alertness), and Negative Affect (NA; measures distress and negative emotions like anger and anxiety).
Measured: Week 1 (prior to dose 1) and at EOT (end of treatment/week 8)
Alcohol craving measure 2
As measured by the Penn Alcohol Craving Scale (PACS). 5-item self-report questionnaire that evaluates alcohol craving over the past week. Measures frequency, intensity, duration of craving, perceived control over drinking, and overall craving severity. Each item is rated on a 7-point Likert scale (0-6). Total scores range from 0 to 30, with higher scores indicating greater craving.
Measured: 12 weeks - measured weekly from baseline (week 1) to outcomes/discharge (week 12)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2025
- Study start15 Jan 2026 (estimated)
- Primary completion15 May 2027 (estimated)
- Study completion15 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol Use Disorder (AUD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase II, double blind, placebo-controlled RCT designed to assess the efficacy (on alcohol consumption, craving and cardiometabolic outcomes) and safety of tirzepatide for individuals with alcohol use disorder and overweight/obesity (AUD-OOB). Participants will receive 8 weekly doses of tirzepatide or placebo (from visit 2, week 1 to visit 9, week 8) administered sub-cutaneously combined with structured "Take Control" CBT sessions (from visit 2, week 1 to visit 10, week 8), followed by follow-up assessments.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- South West Sydney Local Health District
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sydney
- Responsible party
- Principal investigator, Kirsten Morley BPsych MPH PhD, South West Sydney Local Health District
- Investigators
- Paul Haber, MD, RACP, FAChAM, Principal investigator, Sydney Local Health District
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07292519
- Sponsor's protocol ID
- X25-0171
- Status last verified
- Dec 2025
- First submitted
- 1 Dec 2025
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tirzepatide Combined With Cognitive-Behavioural Therapy (CBT) for Adults With Alcohol Use Disorder (AUD) and Overweight/Obesity (OOB)
- ClinicalTrials.gov ID
- NCT07292519
- Acronym / sponsor ID
- X25-0171
- Keywords
- Alcohol Use Disorder (AUD), Overweight or Obese, Concurrent Treatment of AUD and overweight/obesity, Tirzepatide, Phase II Double-blind RCT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- South West Sydney Local Health DistrictUniversity, hospital or other
- Collaborators
- University of Sydney
- Study start
- 15 Jan 2026 (estimated)
- Primary completion
- 15 May 2027 (estimated)
- Study completion
- 15 Jan 2028 (estimated)
- First posted
- 18 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
The primary aim of this clinical trial is to examine the effects of weekly tirzepatide (2.5 mg for 4 weeks followed by 5 mg for 4 weeks) versus placebo injections, in combination with a structured behavioural intervention (Take Control) on alcohol consumption in adults with alcohol use disorder and overweight/obesity (AUD-OOB). The main question[s] it aims to answer are:
- Main outcome: To determine the efficacy of Tirzepatide on alcohol related outcomes, the change in the number of heavy drinking days during the final four weeks of treatment (week 5 - 8, with a final assessment at week 9) will be assessed by comparison with baseline (28 days prior to baseline visit). Researchers will compare tirzepatide to placebo injections (a look-alike substance that contains no drug) to see if weekly tirzepatide administration can reduce the number of heavy drinking days.
- Secondary Outcomes:
- To evaluate changes in additional alcohol-related outcomes:
- Number of drinks per drinking day measured using the Timeline Follow Back
- Number of abstinent days measured using the Timeline Follow Back
- WHO drinking risk level
- Weekly alcohol craving
- Proportion of participants with zero heavy drinking days (Weeks 5-8) ii) To evaluate changes in cardiometabolic indices from baseline to Week 9:
- Body weight
- Waist circumference
- Blood pressure
- HbA1c
- Total cholesterol
- Triglycerides
- 10-year ASCVD risk score iii) To assess safety outcomes associated the delivery of Tirzepatide, investigators will measure the:
- Frequency and severity of side effects (graded using CTCAE V5.0 and monitored continuously throughout the intervention).
- Number of serious adverse events (SAEs)
- Treatment-related discontinuation Participants will complete additional neurobiological assessments including functional magnetic resonance imaging (fMRI) and laboratory-based psychophysiology at two timepoints: baseline (pre-treatment) and the final treatment visit (Week 8), which coincides with the final tirzepatide/placebo dose and final Take Control session. These measures will assess changes in brain activity and autonomic responses to alcohol and food cues.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Phase II, double blind, placebo-controlled RCT designed to assess the efficacy (on alcohol consumption, craving and cardiometabolic outcomes) and safety of tirzepatide for individuals with alcohol use disorder and overweight/obesity (AUD-OOB). Participants will receive 8 weekly doses of tirzepatide or placebo (from visit 2, week 1 to visit 9, week 8) administered sub-cutaneously combined with structured "Take Control" CBT sessions (from visit 2, week 1 to visit 10, week 8), followed by follow-up assessments.
| Arm | Type | Receives |
|---|---|---|
| Tirzepatide: subcutaneous administration of Tirzepatide plus CBT ("Take Control" program) | Experimental | Drug: Tirzepatide, Behavioral: Take Control CBT Module1 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. |
| Placebo: subcutaneous administration of placebo plus CBT ("Take Control" program) | Placebo comparator | Behavioral: Take Control CBT Module, Other: Placebo1 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. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- Body mass index (BMI) ≥27 kg/m²
- Currently motivated to reduce or stop drinking but not engaged in formal AUD treatment
Key exclusion criteria (37 listed)
- 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:
- Currently engaged in pharmacological or behavioral treatment for AUD, or prior engagement within the past 3 months
- History or current diagnosis of:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirzepatideAlso: GLP-1/GIP receptor dual agonistSubcutaneous 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). | Drug | Tirzepatide: subcutaneous administration of Tirzepatide plus CBT ("Take Control" program) |
| Take Control CBT ModuleAlso: Take Control Cognitive Behavioural Therapy ModuleThe 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. | Behavioural | Placebo: subcutaneous administration of placebo plus CBT ("Take Control" program), Tirzepatide: subcutaneous administration of Tirzepatide plus CBT ("Take Control" program) |
| PlaceboParticipants 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. | Other | Placebo: subcutaneous administration of placebo plus CBT ("Take Control" program) |
Primary outcome
Heavy Drinking Days
Time frame: 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.
16 secondary outcomes
Number of drinks per drinking day consumed
Time frame: 12 weeks (weekly, from baseline visit to final follow-up visit at week 12)
Abstinent days
Time frame: 12 weeks (weekly, from baseline visit to final follow-up visit at week 12)
Alcohol Craving
Time frame: 12 weeks (weekly, from baseline visit to final follow-up visit at week 12)
WHO drinking risk level scale.
Time frame: 12 weeks (weekly, from baseline visit to final follow-up visit at week 12)
Proportion of participants with zero heavy drinking days
Time frame: 4 weeks (weeks 5 to 8)
Body weight
Time frame: Measured at baseline [week 0] and at end of treatment [week 9].
Waist circumference
Time frame: Measured at baseline [week 0] and at end of treatment [week 9]
Blood pressure
Time frame: 9 weeks (weekly, from baseline visit to final dose at week 8)
HbA1c
Time frame: 3 weeks (Measured at baseline [week 0] and at end of treatment [week 9], and week 12 if clinically indicated)
10-year ASCVD risk score
Time frame: Measured at baseline [week 0] and end of treatment [week 9].
Frequency and severity of side effects/adverse events (AEs)
Time frame: 12 weeks (at each visit)
Number of treatment-related discontinuation
Time frame: 12 weeks (at each visit)
Total cholesterol
Time frame: 3 weeks (Measured at baseline [week 0] and at end of treatment [week 9], and week 12 if clinically indicated)
Triglycerides
Time frame: 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
Time frame: Week 1 (prior to dose 1) and at EOT (end of treatment/week 8)
Alcohol craving measure 2
Time frame: 12 weeks - measured weekly from baseline (week 1) to outcomes/discharge (week 12)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paul Haber, MD, RACP, FAChAM principal investigator
Sydney Local Health District
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tirzepatide in people with Alcohol Use Disorder (AUD) and Overweight or Obese, run by South West Sydney Local Health District at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kirsten C Morley, PhD (+61295153636, Kirsten.morley@sydney.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heavy Drinking Days (time frame: 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]).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.