The effect of semaglutide therapy on hepatic fat content and on the acute response of liver fat to high-fat load

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Klinicke A Experimentalni Mediciny

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2023-06-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Agentura pro zdravotnický výzkum České republiky

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

- to determine whether the treatment with semaglutide for 16 weeks favorably affects hepatic fat volume
- to determine whether the treatment with semaglutide for 16 weeks favorably affects the acute response of hepatic fat content to a high-fat load

Secondary objectives 4

1. - to determine whether the treatment with semaglutide for 16 weeks results in weight loss in obese subjects
2. - to determine whether the treatment with semaglutide for 16 weeks results in an improvement of insulin sensitivity assessed using HOMA-IR in obese patients
3. - to determine how the treatment with semaglutide for 16 weeks affects the response of triglyceride (TG), glucose, nonesterified fatty acids (NEFA), β-hydroxybutyrate, insulin and glucagon to a high-fat load and to a high-fat load with repeated co-administration of glucose
4. - to try to identify mediators of the effect of semaglutide on fat accumulation in the liver

Conditions and MedDRA coding

Obesity

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. sex: male
2. age 18 – 70 years
3. BMI ≥ 30 kg/m2
4. waist circumference ≥102 cm
5. hepatic fat content evaluated by MRS during screening > 5,5 %

Exclusion criteria 20

1. diabetes mellitus Type I and Type II
2. HbA1c ≥ 48 mmol/mol or fasting glycemia ≥ 7 mmol/l during screening
3. triglyceride > 4 mmol/l during screening
4. acute myocardial infarction, unstable angina pectoris, stroke, pulmonary embolism during 3 months before the start of study
5. heart failure NYHA IV.
6. untreated thyreopathy
7. active hepatitis, liver cirrhosis
8. acute or chronic pancreatitis
9. chronic renal insufficiency IV-V (eGFR ≤ 0,5 ml/s), end-stage renal failure, hemodialysis or peritoneal dialysis
10. active malignancy
11. history of liver transplantation or transplantation of insulin-producing tissue
12. chronic treatment with corticosteroids or immunosuppressants
13. any other disease that, in the opinion of investigator, could endanger or disadvantage the patient if he were to participate in the clinical trial
14. alcohol consumption > 40 g/day
15. lactose intolerance, cow milk protein allergy or other intolerancies
16. significant change in weight (> 5 %) in the 3 months before the entering study
17. use of weight loss dugs
18. hypersensitivity to the active substance or to any auxiliary substance of investigational medicinal product
19. lack of legal capacity
20. refusal to sign informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. hepatic fat content assessed by magnetic resonance spectroscopy (MRS) and hepatic fat volume (= liver volume * hepatic fat content) determined after 14 and 16 weeks of intervention (average value from 2 examinations performed before high-fat load)
2. acute response of hepatic fat content (assessed by MRS) to high-fat load (cream, 150 g of fat) and to a high-fat load co-administered with glucose (3 x 50 g in 2-hour intervals) – hepatic fat content will be measured before and 6 hours after high-fat load (ΔHFC = HFC6 = HFC0, where HFC0 is the hepatic fat content before fat load and HFC6 the hepatic fat content 6 hours after fat load expressed in volume %)

Secondary endpoints 3

1. body weight, waist circumference, body composition (Inbody), the quantity of subcutaneous and visceral fat assessed by MR, and BMI assessed after 14 and 16 weeks of intervention
2. insulin resistence assessed as HOMA-IR after 14 and 16 weeks of intervention
3. the change of concentration of adipokines and other metabolic factors that could expleain the effects of semaglutide on liver fat (adiponectin, leptin, etc.)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Klinicke A Experimentalni Mediciny

Sponsor organisation

Institut Klinicke A Experimentalni Mediciny

Address

Videnska 1958, Krc Krc

City

Prague 4

Postcode

140 00

Country

Czechia

Scientific contact point

Organisation

Institut Klinicke A Experimentalni Mediciny

Contact name

Prof. MUDr. Martin Haluzík, DrSc.

Public contact point

Organisation

Institut Klinicke A Experimentalni Mediciny

Contact name

RNDr. Jan Kovář, CSc.

Locations

1 EU/EEA country · 1 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

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