Clinical trial NCT06939088: Effects of Tirzepatide on Alcohol Intake in Patients Diagnosed With Schizophrenia and Alcohol Use Disorder
Official title: Effect of Tirzepatide on Alcohol Intake and Reward Processing in Patients Diagnosed With Schizophrenia and Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alcohol Use Disorder
Alcohol Abuse/Dependence
Alcohol Dependence
Alcoholism
Schizophrenia Disorders
Schizophrenia and Disorders With Psychotic Features
Schizophrenia and Schizophrenia Spectrum Psychosis
Schizophrenia
Keywords: GLP-1
Glucagon-like peptide 1
fMRI
GIP
Glucose-dependent Insulinotropic Polypeptide
Tirzepatide
Mounjaro(R)
schizophrenia
alcohol
alcohol use disorder
dual diagnosis
Lead sponsor: Psychiatric Centre Rigshospitalet
Sponsor class: OTHER
First posted: 2025-04-22
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for the treatment of type 2 diabetes and obesity, have shown promise as a novel treatment for alcohol use disorder (AUD). This study aims to investigate whether the Glucose-dependent Insulinotropic Polypeptide/GLP-1RA tirzepatide will reduce alcohol consumption in patients with a dual diagnosis of AUD and schizophrenia, a population in dire need of improved treatment options. To further investigate the neurobiological underpinnings of a potential dampening effect on alcohol consumption, functional magnetic resonance imaging (fMRI) brain scans will be applied.

The key anticipated outcomes include:

* decreased alcohol consumption and
* reduced alcohol cue-induced brain activity in the GIP/GLP-1-treated patient group compared with the placebo group. To the best of the investigators knowledge, this has never been examined before.

Detailed description: The study is a randomised (1:1), double-blinded, placebo-controlled clinical trial including 26 weeks of treatment investigating whether tirzepatide vs placebo can reduce the number of heavy drinking days in patients with comorbid diagnoses of schizophrenia and AUD. The primary endpoint will be evaluated after 16 weeks of treatment. The study will conclude after a post-intervention follow-up 14 weeks after last treatment at week 40 of the study.

108 participants will be included. Alcohol consumption and secondary endpoints will be assessed at weeks 0, 4, 8, 12, 16, 20, 26, and 40, and all patients will be offered 6 sessions of supportive therapy, while participating in the study.

The randomisation and administration of the weekly injections (tirzepatide/placebo) will be administered by an unblinded staff not involved in other trial activities. All patients will be blindfolded when receiving the injections. Eligible patients (n=50) will have an fMRI brain scan performed at baseline and in week 16. Blood tests for safety measures and secondary endpoint-measures will be performed at weeks 0, 16, 26, and 40.

Eligibility criteria: Inclusion Criteria:

* Informed Consent: The patient must provide both oral and written informed consent.
* Diagnosis:

  * Diagnosed with alcohol dependence according to the International Classification of Diseases, 10th Edition (ICD-10), and alcohol use disorder as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
  * Diagnosed with schizophrenia spectrum disorder according to ICD-10 and DSM-5
* AUDIT Score: Alcohol Use Disorder Identification Test (AUDIT) score greater than 15.
* Body Mass Index (BMI): BMI of 23 kg/m² or higher.
* Age Range: Between 18 and 70 years old (inclusive).
* Heavy Alcohol Consumption: Defined as 4 or more heavy drinking days within a consecutive 21-day period during the 28 days preceding the baseline evaluation. The 21-day period will be selected based on the largest total alcohol consumption and the greatest number of heavy drinking days within the 28-day timeframe. This will be assessed using the Timeline Followback (TLFB) method. Heavy drinking days are defined as days with an alcohol intake of 4 or more units (48 g of alcohol) for women and 5 or more units (60 g of alcohol) for men.

Exclusion Criteria:

* Intellectual Disability: individuals with a diagnosis of intellectual disability.
* Acute Psychosis: Acute exacerbation of psychosis, as indicated by a score of 6 or 7 on the Clinical Global Impression-Severity (CGI-S) scale.
* Coercive Measures: Current use of coercive measures, which includes individuals sentenced to treatment ('dom til behandling').
* Suicidal Behaviour: Evidence of current severe suicidal behaviour, as assessed by the investigator during clinical evaluation.
* History of Severe Alcohol Withdrawal: History of delirium tremens or alcohol withdrawal seizures.
* Severe Withdrawal Symptoms: Clinical Institute Withdrawal Assessment of Alcohol Scale, revised (CIWA-Ar) score greater than 9 at baseline examination.
* Severe Neurological Conditions: Presence of severe neurological diseases, including severe traumatic brain injury.
* Diabetes: Type 1 or 2 diabetes
* Pregnant or Potentially Pregnant Women: WOCBP who are pregnant, breastfeeding, intend to become pregnant within the next 6 months (including 16 weeks of treatment plus two months after discontinuation of semaglutide), or are not using a highly effective contraceptive method throughout the study period. Highly effective methods include combined hormonal contraception (oral, intravaginal, transdermal), progestogen-only hormonal contraception (oral, injectable, implantable), intrauterine device (IUD), intrauterine system (IUS), bilateral tubal occlusion, vasectomised partner, or sexual abstinence. WOCBP with a measured serum human chorionic gonadotropin (hCG) level greater than 3 U/L at inclusion will also be excluded.
* Liver Function: Impaired hepatic function, defined as liver transaminases greater than three times the upper limit of normal.
* Renal Function: Impaired renal function, indicated by an estimated glomerular filtration rate (eGFR) below 50 mL/min and/or plasma creatinine above 150 μmol/L.
* Pancreatic Function: History of acute or chronic pancreatitis or amylase levels more than twice the upper limit of normal.
* Thyroid Conditions: Previous medullary thyroid carcinoma (MTC) or a family history of MTC and/or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
* Cardiac Issues: Decompensated heart failure (NYHA class III or IV), unstable angina pectoris, or myocardial infarction within the past 12 months.
* Uncontrolled Hypertension: Systolic blood pressure above 180 mmHg or diastolic blood pressure above 110 mmHg.
* Alcohol Use Disorder Medication: Use of medications for alcohol use disorder (e.g., disulfiram, naltrexone, acamprosate, nalmefene) within the 28 days prior to inclusion as recorded in the Timeline Followback (TLFB) schedule.
* Investigational Drugs: Receipt of any investigational drug within the past three months.
* Weight-Lowering Medications: Use of other weight-lowering pharmacotherapy in the past three months.
* Allergic Reactions: Hypersensitivity to the active substance or any of the excipients.
* Language Barriers: Inability to speak and/or understand Danish.
* Other Conditions: Any other condition that, in the investigator\&#39;s opinion, may interfere with participation in the trial.

For the subgroup of participants undergoing brain scans:

* MRI Contraindications: any contraindications for MRI (e.g., magnetic implants, pacemaker, claustrophobia).
* Benzodiazepine Use: Intermittent use of benzodiazepines within 12 days prior to the scanning session is not allowed. However, regular use of a stable dose of benzodiazepines is permitted.

Primary outcomes:
measure: Change in heavy drinking days
timeFrame: From baseline to 16 weeks of treatment
Secondary outcomes:
measure: Total alcohol consumption
timeFrame: From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
measure: Days without alcohol consumption
timeFrame: From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
measure: World Health Organization (WHO) Risk Levels of Alcohol Consumption
timeFrame: From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
measure: Penn Alcohol Craving Scale (PACS) score
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Alcohol Use Disorder Identification Test (AUDIT) score
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Drug Use Disorders Identification Test (DUDIT) score
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Drug use frequency
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Preferred substance of use
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Biomarkers of cannabis exposure
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: The Patient Health Questionnaire (PHQ-9)
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Fagerströms Test for Nicotine Dependence score
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Number of cigarettes smoked per day
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Cotinine levels
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Blood parameters
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Liver fibrosis (FIB-4 score)
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Blood phosphatidyl ethanol (PEth) levels
timeFrame: From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
measure: Glycaemic control parameters
timeFrame: From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
measure: Blood pressure
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Body weight
timeFrame: From baseline to 16 and 26 weeks of treatment and 14 weeks post-intervention
measure: Waist circumference
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: fMRI alcohol cue-reactivity
timeFrame: From baseline to 16 weeks of treatment
measure: Schizophrenia Quality of Life Scale (SQLS)
timeFrame: From baseline to 26 weeks of treatment
measure: Global Assessment of Psychosocial Disability (GAPD)
timeFrame: From baseline to 26 weeks of treatment
measure: Positive and Negative Syndrome Scale (PANSS-6)
timeFrame: From baseline to 26 weeks of treatment
measure: Clinical Global Impression Severity Scale (CGI-S)
timeFrame: From baseline to 26 weeks of treatment
measure: Proteomics
timeFrame: From baseline to 16 and 26 weeks of treatment
measure: Qualitative experience
timeFrame: From baseline to 16 weeks of treatment
Other outcomes:
measure: Safety Outcome
timeFrame: From baseline to 16 and 26 weeks of treatment
Locations:
city: Aalborg
country: Denmark
facility: Department of Psychiatry, Aalborg University Hospital
city: Frederiksberg
country: Denmark
facility: Psychiatric Center Copenhagen, Frederiksberg Hospital
Study officials:
affiliation: Mental Healt h Service Centre Copenhagen , Frederiksberg Hospital, NP Lab
name: Anders Fink-Jensen, MD, DMSc, Professor
role: PRINCIPAL_INVESTIGATOR
References: