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Tirzepatide Combined With Cognitive-Behavioural Therapy (CBT) for Adults With Alcohol Use Disorder (AUD) and Overweight/Obesity (OOB)

S

South West Sydney Local Health District

Status and phase

Not yet enrolling
Phase 2

Conditions

Alcohol Use Disorder (AUD)
Comorbidities and Coexisting Conditions
Overweight or Obese

Treatments

Other: Placebo
Behavioral: Take Control CBT Module
Drug: Tirzepatide

Study type

Interventional

Funder types

Other

Identifiers

NCT07292519
X25-0171

Details and patient eligibility

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.

Full 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:

  1. 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.

  2. Secondary Outcomes:

    i) 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.

Enrollment

46 estimated patients

Sex

All

Ages

21 to 75 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

46 participants in 2 patient groups, including a placebo group

Tirzepatide: subcutaneous administration of Tirzepatide plus CBT ("Take Control" program)
Experimental group
Description:
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.
Treatment:
Drug: Tirzepatide
Behavioral: Take Control CBT Module
Placebo: subcutaneous administration of placebo plus CBT ("Take Control" program)
Placebo Comparator group
Description:
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.
Treatment:
Behavioral: Take Control CBT Module
Other: Placebo

Trial contacts and locations

1

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Central trial contact

Kirsten C Morley, PhD

Data sourced from clinicaltrials.gov

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