Can treatment with tirzepatide reduce alcohol intake in individuals diagnosed with schizophrenia and alcohol use disorder (DUALPSYCHIATRY)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Psykiatrisk Center Kobenhavn

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

1 May 2025 → ongoing

Decision date (initial)

2025-04-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

The Novo Nordisk Foundation · The Danish Independent Research Fund

External identifiers

EU CT number

2024-518608-28-00

WHO UTN

U1111-1312-8134

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

This study will examine the effects of tirzepatide vs. placebo on alcohol consumption in patients diagnosed with schizophrenia and alcohol use disorder.

Conditions and MedDRA coding

Schizophrenia and Alcohol Use Disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Informed Consent: The patient must provide both oral and written informed consent.
2. Diagnosis: o 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). o Diagnosed with schizophrenia spectrum disorder according to ICD-10 and DSM-5
3. AUDIT Score: Alcohol Use Disorder Identification Test (AUDIT) score greater than 15.
4. Body Mass Index (BMI): BMI of 23 kg/m² or higher.
5. Age Range: Between 18 and 70 years old (inclusive).
6. 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 22

1. - Intellectual Disability: individuals with a diagnosis of intellectual disability.
2. - Acute Psychosis: Acute exacerbation of psychosis, Severe acute exacerbation of psychosis, as assessed by the investigator during clinical evaluation
3. - Coercive Measures: Current use of coercive measures, which includes individuals sentenced to treatment (‘dom til behandling’).
4. - Suicidal Behaviour: Evidence of current severe suicidal behaviour, as assessed by the investigator during clinical evaluation.
5. - History of Severe Alcohol Withdrawal: History of delirium tremens or alcohol withdrawal seizures.
6. - Severe Withdrawal Symptoms: Clinical Institute Withdrawal Assessment of Alcohol Scale, revised (CIWA-Ar) score greater than 9 at baseline examination.
7. - Severe Neurological Conditions: Presence of severe neurological diseases, including severe traumatic brain injury.
8. - Diabetes: Type 1 or 2 diabetes
9. - Pregnant 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
10. - Liver Function: Impaired hepatic function, defined as liver transaminases greater than three times the upper limit of normal.
11. - 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.
12. - Pancreatic Function: History of acute or chronic pancreatitis or amylase levels more than twice the upper limit of normal.
13. - Thyroid Conditions: Previous medullary thyroid carcinoma (MTC) or a family history of MTC and/or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
14. - Cardiac Issues: Decompensated heart failure (NYHA class III or IV), unstable angina pectoris, or myocardial infarction within the past 12 months.
15. - Uncontrolled Hypertension: Systolic blood pressure above 180 mmHg or diastolic blood pressure above 110 mmHg.
16. - 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.
17. - Investigational Drugs: Receipt of any investigational drug within the past three months.
18. - Weight-Lowering Medications: Use of other weight-lowering pharmacotherapy, including tirzepatide or other GLP-1 RA, in the past three months.
19. - Allergic Reactions: Hypersensitivity to the active substance or any of the excipients.
20. - Language Barriers: Inability to speak and/or understand Danish.
21. - Other Conditions: Any other condition that, in the investigator's opinion, may interfere with participation in the trial.
22. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 27

1. Changes from baseline to after 16 weeks and after 26 weeks of treatment in total alcohol consumption measured using the TLFB method
2. Changes from baseline to after 16 weeks and after 26 weeks of treatment in number of days without alcohol measured using the TLFB method.
3. 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.
4. 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.
5. Changes from baseline to after 16 weeks and after 26 weeks of treatment in Alcohol Use Disorders Identification Test (AUDIT)-score
6. Changes from baseline to after 16 weeks and after 26 weeks of treatment in Drug Use Disorders Identification Test (DUDIT)-score
7. Changes from baseline to after 26 weeks of treatment in quality of life measured using the Schizophrenia Quality of Life Scale (SQLS)
8. Changes from baseline to after 26 weeks of treatment in Clinical Global Impression Severity Scale (CGI-S)
9. Changes from baseline to after 26 weeks of treatment in Global Assessment of Psychosocial Disability (GAPD)
10. 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)
11. Changes from baseline to after 16 and after 26 weeks of treatment in the Patient Health Questionnaire (PHQ-9) score
12. Changes from baseline to after 16 weeks and after 26 weeks of treatment in smoking habits using the Fagerströms Test for Nicotine Dependence score
13. Changes from baseline to after 16 weeks and after 26 weeks of treatment in blood parameters (GGT, ALAT, MCV)
14. Changes from baseline to after 16 weeks and after 26 weeks of treatment in blood phosphatidyl ethanol (PEth) levels
15. Changes from baseline to after 16 weeks and after 26 weeks of treatment in body weight and waist circumference
16. Changes from baseline to after 16 weeks and after 26 weeks of treatment in blood pressure and pulse
17. Changes from baseline to after 16 weeks and after 26 weeks of treatment in glycemic parameters (HbA1c)
18. Changes from baseline to after 16 weeks and after 26 weeks of treatment in risk of liver fibrosis measured using the FIB-4 index
19. Changes from baseline to after 16 weeks and after 26 weeks of treatment in proteomics
20. 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
21. Changes from baseline to after 16 weeks and after 26 weeks of treatment in blood cotinine levels
22. Changes from baseline to after 16 weeks and after 26 weeks of treatment in average number of cigarettes smoked per day
23. Changes from baseline to after 16 weeks and after 26 weeks of treatment in preferred substance of use
24. 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.
25. 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
26. Changes from baseline to after 26 weeks of treatment in per cent heavy drinking days assessed using the TLFB method
27. Changes from baseline to after 16 weeks and after 26 weeks of treatment in the drug use frequency section of the DUDIT-extended

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Psykiatrisk Center Kobenhavn

Sponsor organisation

Psykiatrisk Center Kobenhavn

Address

Edel Sauntes Alle 10

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Psykiatrisk Center Kobenhavn

Contact name

Søren Brøgger Jensen

Public contact point

Organisation

Psykiatrisk Center Kobenhavn

Contact name

Søren Brøgger Jensen

Third parties 3

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications