Tirzepatide for Schizophrenia | Alcohol use disorder

Inclusion criteria

• {"criterion_text":"- Informed Consent: The patient must provide both oral and written informed consent.\n- Diagnosis: o\tDiagnosed 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). o\tDiagnosed with schizophrenia spectrum disorder according to ICD-10 and DSM-5\n- AUDIT Score: Alcohol Use Disorder Identification Test (AUDIT) score greater than 15.\n- Body Mass Index (BMI): BMI of 23 kg/m² or higher.\n- Age Range: Between 18 and 70 years old (inclusive).\n- 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

• {"criterion_text":"-\tIntellectual Disability: individuals with a diagnosis of intellectual disability.\n-\tAcute Psychosis: Acute exacerbation of psychosis, Severe acute exacerbation of psychosis, as assessed by the investigator during clinical evaluation\n-\tCoercive Measures: Current use of coercive measures, which includes individuals sentenced to treatment (‘dom til behandling’).\n-\tSuicidal Behaviour: Evidence of current severe suicidal behaviour, as assessed by the investigator during clinical evaluation.\n-\tHistory of Severe Alcohol Withdrawal: History of delirium tremens or alcohol withdrawal seizures.\n-\tSevere Withdrawal Symptoms: Clinical Institute Withdrawal Assessment of Alcohol Scale, revised (CIWA-Ar) score greater than 9 at baseline examination.\n-\tSevere Neurological Conditions: Presence of severe neurological diseases, including severe traumatic brain injury.\n-\tDiabetes: Type 1 or 2 diabetes\n-\tPregnant or potentially pregnant women: Women of childbearing potential (WOCBP) who are pregnant, breastfeeding, intend to become pregnant within the next eight months (including 26 weeks of treatment plus two months after discontinuation of tirzepatide), 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\n-\tLiver Function: Impaired hepatic function, defined as liver transaminases greater than three times the upper limit of normal.\n-\tRenal Function: Impaired renal function, indicated by an estimated glomerular filtration rate (eGFR) below 50 mL/min and/or plasma creatinine above 150 μmol/L.\n-\tPancreatic Function: History of acute or chronic pancreatitis or amylase levels more than twice the upper limit of normal.\n-\tThyroid Conditions: Previous medullary thyroid carcinoma (MTC) or a family history of MTC and/or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).\n-\tCardiac Issues: Decompensated heart failure (NYHA class III or IV), unstable angina pectoris, or myocardial infarction within the past 12 months.\n-\tUncontrolled Hypertension: Systolic blood pressure above 180 mmHg or diastolic blood pressure above 110 mmHg.\n-\tAlcohol 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.\n-\tInvestigational Drugs: Receipt of any investigational drug within the past three months.\n-\tWeight-Lowering Medications: Use of other weight-lowering pharmacotherapy, including tirzepatide or other GLP-1 RA, in the past three months.\n-\tAllergic Reactions: Hypersensitivity to the active substance or any of the excipients.\n-\tLanguage Barriers: Inability to speak and/or understand Danish.\n-\tOther Conditions: Any other condition that, in the investigator's opinion, may interfere with participation in the trial.\n-For the subgroup of participants undergoing brain scans: -\tMRI Contraindications: any contraindications for MRI (e.g., magnetic implants, pacemaker, claustrophobia). -\tBenzodiazepine 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 endpoints

• {"endpoint_text":"- The primary endpoint will be a change in alcohol consumption, measured as a per cent change in heavy drinking days (days with an excess alcohol intake of 60 grams for men and 48 grams for women) after 16 weeks of treatment with tirzepatide or placebo, adjusted for the value at baseline (percentage points). Heavy drinking days will be registered using the validated Timeline-Follow-Back (TLFB) method.","definition_or_measurement_approach":"Change in percent heavy drinking days after 16 weeks versus baseline, adjusted for baseline; heavy drinking days registered using the Timeline-Follow-Back (TLFB) method (60 g men / 48 g women)."}

Secondary endpoints

• {"endpoint_text":"- Changes from baseline to after 16 weeks and after 26 weeks of treatment in total alcohol consumption measured using the TLFB method\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in number of days without alcohol measured using the TLFB method.\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in World Health Organisation (WHO) alcohol risk level measured using the TLFB method.\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in alcohol craving score using the Penn Alcohol Craving Scale (PACS) score.\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in Alcohol Use Disorders Identification Test (AUDIT)-score\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in Drug Use Disorders Identification Test (DUDIT)-score\n- Changes from baseline to after 26 weeks of treatment in quality of life measured using the Schizophrenia Quality of Life Scale (SQLS)\n- Changes from baseline to after 26 weeks of treatment in Clinical Global Impression Severity Scale (CGI-S)\n- Changes from baseline to after 26 weeks of treatment in Global Assessment of Psychosocial Disability (GAPD)\n- Changes from baseline to after 26 weeks of treatment in symptom severity of schizophrenia measured using the six-item Positive and Negative Syndrome Scale (PANSS-6)\n- Changes from baseline to after 16 and after 26 weeks of treatment in the Patient Health Questionnaire (PHQ-9) score\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in smoking habits using the Fagerströms Test for Nicotine Dependence score\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in blood parameters (GGT, ALAT, MCV)\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in blood phosphatidyl ethanol (PEth) levels\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in body weight and waist circumference\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in blood pressure and pulse\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in glycemic parameters (HbA1c)\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in risk of liver fibrosis measured using the FIB-4 index\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in proteomics\n- For a subgroup of participants (n=50), fMRI will be conducted at baseline and after 16 weeks of treatment to evaluate: Changes in fMRI BOLD signals in response to alcohol cues in brain regions related to reward and mood and changes in resing state fMRI\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in blood cotinine levels\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in average number of cigarettes smoked per day\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in preferred substance of use\n- For a subgroup of participants (n=10), qualitative interviews will be performed after 16 weeks of treatment to evaluate qualitative differences in trial participation experiences between the intervention and placebo groups, which will be assessed as a secondary outcome.\n- Changes in biomarkers of recent cannabis exposure (blood 11-hydroxy-delta 9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH) levels) from baseline to after 16 and 26 weeks of treatment\n- Changes from baseline to after 26 weeks of treatment in per cent heavy drinking days assessed using the TLFB method\n- Changes from baseline to after 16 weeks and after 26 weeks of treatment in the drug use frequency section of the DUDIT-extended","definition_or_measurement_approach":"Secondary endpoints are changes from baseline measured at 16 and/or 26 weeks using validated instruments specified per endpoint (e.g., TLFB for alcohol consumption and heavy drinking days; PACS for craving; AUDIT/DUDIT for screening; SQLS, CGI-S, GAPD, PANSS-6, PHQ-9, Fagerström Test for nicotine dependence; blood biomarkers GGT/ALAT/MCV/PEth/HbA1c/PEth/FIB-4; proteomics; cotinine; fMRI BOLD responses for subgroup n=50; qualitative interviews for subgroup n=10)."}

Methods

• Posting on regional research portals (e.g., RHP research portal) targeted at potential participants in Denmark (document: K2_Recruitment material_Tekst til RHP research portal).
• Posting on alcohol-research related websites (e.g., 'alkoholforskningdk') targeted to persons with alcohol use concerns in Denmark (document: K2_Recruitment material_tekst til alkoholforskningdk).
• Electronic invitations via EBOKS (Danish national secure digital mail) to potential participants (document: K2_recruitment material_EBOKS invitation).
• Use of printed recruitment materials such as posters and folders distributed at clinical sites (documents: K2_Recruitment material_Rekrutteringsplakat; K2_Recruitment material_Rekrutteringsfolder).
• Use of trial-specific outreach materials (trialtree material) and recruitment procedure documents (document: K2_Recruitment material_trialtree_material; informedconsent_patientrecruitmentprocedure).

Denmark

Earliest CTIS Part Ii Submission Date

26-03-2025

Latest Decision Or Authorization Date

07-01-2026

Processing Time Days

287

Number Of Sites

2

Number Of Participants

108

Primary sponsor

Full Name

Psykiatrisk Center Kobenhavn

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Aalborg University Hospital","duties_or_roles":"sponsorDuties code: 2","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Denmark","full_name":"Aalborg University Hospital","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}