An interventional, multi-center, randomized, double blinded, placebo controlled study to investigate semaglutide add-on treatment for metabolic control in antipsychotic-using patients (STABIL-NOR – study).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Helse Bergen HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

19 Oct 2024 → ongoing

Decision date (initial)

2024-10-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Helse Vest research funding

External identifiers

EU CT number

2023-506109-20-00

EudraCT number

2021-004452-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the effect of semaglutide s.c. 2.4 mg once-weekly versus semaglutide placebo in patients with schizophrenia spectrum disorders and a BMI of equal to or above 30 kg/m2 or BMI equal to or above 27 kg/m2 in addition to prediabetes determined by FPG between 5.6 and 6.9 mmol/l and/or HbA1c between 39-47 mmol/mol (on two occasions at least 24 hours apart) on body weight.

Secondary objectives 1

1. To compare the effect of semaglutide, in the patient population and administered as described under "main objective", on • fasting blood glucose/ HbA1c/ triglycerides/ cholesterols • time until discontinuation of antipsychotic drug treatment • perceived body image • cognition • economic outcomes • body fat measures • heart rate and blood pressure • development of diabetes mellitus type 2 • depressive symptoms

Conditions and MedDRA coding

Metabolic control in antipsychotic-using patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, also including activities to determine suitability for the trial as for example the screening for eligibility.
2. Men or woman aged between 18 and 70 years, both years included, at the time of signing informed consent.
3. BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with the presence of prediabetes determined with either fasting plasma glucose (FPG) between 5.6 and 6.9 mmol/l and/or HbA1c between 39-47 mmol/mol measured on two occasions at least 24 hours apart. These measures will be done at the V1 and the V2 visit, or alternatively a measurement of FPG or HbA1c within the borders of prediabetes performed in the regular clinical treatment during last 2 weeks before screening can be used as the first of the two occasions.
4. A diagnosis within the schizophrenia-spectrum according to International classification of diseases version - 10 (ICD-10): F 20, F 22, F 23, F 25, F 28, F 29.
5. AP drug use for at least 3 weeks prior to starting study medication and a treatment plan/recommendation for further AP drug use for at least the next 6 months. Antipsychotic drug discontinuation during the trial will not result in exclusion from further participation in the study.

Exclusion criteria 4

1. With relation to glycemic regulation: a. Type 1 or Type 2 diabetes present or in history. b. HbA1c >48 mmol/mol. c. Latent autoimmune diabetes in adults (LADA). d. Treatment with a GLP-1 receptor agonist last 3 months before screening. e. Treatment with insulin last 3 months before screening. f. Treatment with metformin last 4 weeks before drug initiation.
2. Clearly disturbed thyroidal function as in an untreated hypo- or hyperthyroidism.
3. Surgical treatment to reduce weight last 6 months before screening, or planned surgical treatment to reduce weight.
4. Safety criteria: a. a personal or family history of medullary thyreoid cancer or multippel endokrin neoplasi 2 (MEN 2). b. A history of pancreatitis during the last 12 months before inclusion. c. A history of myocardial infarction/instable angina/stroke during the last 12 months before inclusion. d. A prior serious hypersensitivity reaction to semaglutide or to any of the excipients or otherwise as specified in the SPC of Wegovy. e. A history of anorexia nervosa defined: a specialist diagnosed anorexia nervosa of ICD-10 F50.0 or F50.1 last ten years before randomization. f. Woman of childbearing potential (WOCBP) who are not using adequate contraceptive methods (ref. appendix 4, section 10.4.2). Contraception must be continued for 2 months after the stop of study medication. See exception clause in section 10.4.2.1. g. Pregnant woman will, based on a positive pregnancy test, be excluded from participation. h. Breastfeeding. i. Disorders, unwillingness or inability which in the investigator’s opinion might jeopardize the subject’s safety or compliance with the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoints addressing the primary objective: change in body weight from baseline to week 26 of the study

Secondary endpoints 9

1. Change from baseline at week 0 to week 26 in: o HbA1c (%, mmol /mol) o FPG (mmol/l) o Fasting serum insulin (mIU/L) and insulin C peptid o Lipids (mg/dL)  Total cholesterol  High density lipoprotein (HDL) cholesterol  Low density lipoprotein (LDL) cholesterol  Very low density lipoprotein (VLDL) cholesterol  Free fatty acids  Triglycerides
2. Change from baseline at week 0 to week 26 in cognition as assessed by the Brief Assessment of Cognition in Schizophrenia (BACS)
3. Time (in days) until discontinuation of AP drug treatment as evaluated through interviews and the measurement of serum levels of antipsychotic drugs
4. Change from baseline at week 0 to week 26 in the Stunkard scale
5. The economic outcomes will be assessed in the following way: Analysis of incremental cost-effectiveness ratio (ICER) and a cost-utility analysis based on an well-validated instrument to capture changes in quality of life during the intervention period. These outcomes will also use register-data collected during the 12 months after participation in the RCT. Change in quality of life from baseline at week 0 to week 26 will be assessed by the Manchester Short Assesment of quality of life (MANSA).
6. Change from baseline at week 0 to week 26 for waist and hip circumference, waist to hip ratio
7. Change from baseline at week 0 to week 26 in heart rate and blood pressure after 5 minutes at rest
8. Proportion of participants with T2DM at week 26
9. Change from baseline at week 0 to week 26 in the ratings of the Calgary Depression Scale for Schizophrenia (CDSS)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Helse Bergen HF

Sponsor organisation

Helse Bergen HF

Address

Jonas Lies Vei 65

City

Bergen

Postcode

5021

Country

Norway

Scientific contact point

Organisation

Helse Bergen HF

Contact name

Rune Andreas Kroken

Public contact point

Organisation

Helse Bergen HF

Contact name

Rune Andreas Kroken

Third parties 1

Locations

1 EU/EEA country · 4 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 16 files

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

Application history

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