Effects of extensive Weight loss on Insulin resistance and Lipid-kinetics in people with obesity and fatty liver Disease

Phase 1

Recruiting

• Conditions: Obesity, Non-alcoholic Fatty Liver Disease; MedDRA version: 22.0Level: LLTClassification code: 10029530Term: Non-alcoholic fatty liver Class: 10019805; MedDRA version: 20.0Level: PTClassification code: 10029883Term: Obesity Class: 100000004861; MedDRA version: 22.0Level: PTClassification code: 10053219Term: Non-alcoholic steatohepatitis Class: 100000004871; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: CTIS2023-506300-12-00
• Lead Sponsor: Region Midtjylland

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-06-13
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 24

Inclusion Criteria

1. Women who meet the Danish health authorities' criteria for being offered surgical treatment of severe obesity, which are: (i) Body mass index (BMI) over 35 and at least one of the following comorbidities: osteoarthritis in the lower extremities, documented sleep apnea, or severe uncontrolled hypertension, or (ii) extreme obesity with BMI over 50., 2. Age above 18., 3. Understands and speaks Danish., 4. Either MRS/MRI-PDFF with more than 5% steatosis in the liver or a CAP greater than 280 dB/m.

Exclusion Criteria

1., Treatment with GLP-1ra within the last 6 months., 2. Type 1 diabetes or type 2 diabetes, i.e., fasting blood sugar over 7 mmol/L or non-fasting blood sugar over 11.1 mmol/L. , 3. Alcohol consumption of more than 20 g/day, equivalent to approximately 1.5 standard drinks daily., 4. Known liver disease other than NALFD., 5. Known polycystic ovary syndrome., 6. Other uncontrolled medical condition (e.g., thyroid disease, kidney disease) assessed by the investigators., 7. Weight above 170 kg, shoulder width measured at the widest point above 65 cm, or circumference above 160 cm measured at the participant's widest point (as they would not be able to undergo MRS/MRI-PDFF and RYGB without prior weight loss). 8., Recent weight loss or weight gain exceeding 5% of body weight. 9., Contraindication to RYGB (Roux-en-Y gastric bypass)., 10. Pregnancy or women not using reliable contraception., 11. Liver cirrhosis, either known or assessed based on Fibroscan > 14 kPa., 12. Allergy to ingredients in Wegovy®.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: We aim to investigate the changes in very low-density lipoproteins- and triglycerides (VLDL-TG) kinetics before, during, and after extensive weight loss in women diagnosed with both obesity and non-alcoholic fatty liver disease.;Secondary Objective: To study the changes in VLDL-TG kinetics between the two intervention arms during weight loss and 8 months after treatment initiation.;Primary end point(s): Changes in VLDL-TG kinetics 8 months after treatment initiation, when their weight loss has stabilized: I) Changes in relation to the degree of weight loss. II) Changes in relation to the amount of fat in the liver, assessed by MRS/MRI-PDFF.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Changes during and 8 months after treatment initiation compared to baseline and between the groups, in respect to: I) Hepatic secretion of VLDL-TG particles, II) Circulating lipids, III) Insulin resistance, IV) Biochemical markers of inflammation, V) The ratio of neutrophilic granulocytes and lymphocytes, VI) intestinal- and saliva microbiota, VII) The Fibrosis-4 index, VIII) NAFLD fibrosis score and, in the surgical group only, IX) Changes in liver histology and gene expression.