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

NCT07292519 | Not Yet Recruiting Phase 2

• 1 other identifier: X25-0171
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

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

Keywords

Alcohol Use Disorder (AUD); Overweight or Obese; Concurrent Treatment of AUD and overweight/obesity; Tirzepatide; Phase II Double-blind RCT

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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)

• Alcohol Craving

  12 weeks (weekly, from baseline visit to final follow-up visit at week 12)

• WHO drinking risk level scale.

  12 weeks (weekly, from baseline visit to final follow-up visit at week 12)

• Proportion of participants with zero heavy drinking days

  4 weeks (weeks 5 to 8)

Other Outcomes (30)

• Changes in cigarette use

  At baseline (week 0) and at end-of-treatment visit (week 9).

• Changes in cannabis use

  At baseline (week 0) and at end-of-treatment visit (week 9).

• Changes in phosphatidylethanol (PEth), an objective biomarker of alcohol use

  Baseline (Week 0), End-of-treatment (week 9) and optionally at week 12

Study Arms (2)

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.

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.

Behavioral: Take Control CBT Module; Other: Placebo

Interventions

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).

Also known as: GLP-1/GIP receptor dual agonist

Tirzepatide: subcutaneous administration of Tirzepatide plus CBT ("Take Control" program)

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.

Also known as: Take Control Cognitive Behavioural Therapy Module

Placebo: subcutaneous administration of placebo plus CBT ("Take Control" program); Tirzepatide: subcutaneous administration of Tirzepatide plus CBT ("Take Control" program)

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.

Placebo: subcutaneous administration of placebo plus CBT ("Take Control" program)

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• South West Sydney Local Health District: lead
• University of Sydney: collaborator

Study Sites (1)

Drug Health Services, Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

MeSH Terms

Conditions

Alcoholism; Overweight; Obesity

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Paul Haber, MD, RACP, FAChAM

  Sydney Local Health District

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kirsten C Morley, PhD

CONTACT

+61295153636; Kirsten.morley@sydney.edu.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: December 1, 2025
• First Posted: December 18, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): January 15, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)