Characterization and Management of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) (METAfoie)

Characterization and Management of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Through an Individualized Nutritionnal Approach and Semaglutide Therapy.

The goal of this clinical trial is to improve the treatment of hepatic steatosis associated with obesity with pharmacological and nutritionnal approaches. The main question it aims to answer is:

Does an individualized nutritionnal approach with a dietician combined with medication targeting obesity is the most efficient way to treat hepatic steatosis associated with obesity?

Participants will either participate in one of three groups:

• Nutrition: Participant will only have a regular follow-up with a registered dietician;
• Nutrition + Semaglutide: Participants will start a new medication targeting obesity and will have a regular follow-up with a registered dietician;
• Semaglutide: Participants will start a new medication targeting obesity.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Metabolic Associated Fatty Liver Disease; Metabolic Associated-dysfunction Steatohepatitis (MASH)
• Intervention / Treatment: Other: Diet; Drug: semaglutide

Detailed Description

Participants in each group will be followed during a year for 4 timepoints (0, 3, 6 and 12 months). Blood and feces samples, anthropometric measures, transient elastography measurements and health questionnaires will be assessed at each timepoint.

The nutritionnal intervention targeting hepatic steastosis associated with obesity will use conclusions from a systematic review we conducted on nutritionnal approaches to treat liver steatosis.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tristan Rocheleau, RD., M.Sc.; Phone Number: 418-656-8711, #2681; Email: tristan.rocheleau.2@ulaval.ca
• Study Contact Backup: Name: Fannie Lajeunesse-Trempe, MD., Ph.D.; Phone Number: 418-656-8711, #8052; Email: fanny.lajeunesse-trempe.1@ulaval.ca

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 4G5
      • Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
      • Contact: Tristan Rocheleau, RD., Ph.D.(c); Phone Number: 5819969946; Email: tristan.rocheleau.2@ulaval.ca
      • Contact: Fannie Lajeunesse-Trempe, MD., Ph.D.
      • Contact: André Tchernof, Ph.D.
      • Contact: André Marette, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Body mass index between 30 and 50 kg/m2;
• Stade 2 or 3 (S2 or S3) hepatic steatosis with or without liver fibrosis.

Exclusion Criteria:

• Type 1 diabetes diagnosis;
• Alcohol consumption exceeding recommendations [>140 g/week (women) and >210 g/week (men)];
• Known chronic hepatic disease non-steatotic at the entry of the study (Wilson's disease, hemochromatosis, alpha-1-antitrypsin deficiency, viral hepatitis, auto-immune hepatitis, etc.);
• Pharmacological treatment targeting obesity active or ended in the last 3 months;
• Bariatric surgery;
• Gastro-intestinal pathologies (GI cancers, IBD, etc.);
• Capsulated probiotics consumption;
• Antibiotic treatment in the last 3 months;
• Pregnancy;
• Cirrhosis diagnosis (hepatic decompensation).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nutrition; This arm will only participate in an individualized nutritionnal approach.	Other: Diet; Participants receiving this intervention will be seeing a registered dietician at each visit. The individualized approach will be based on recent literature (mostly hypocaloric) by using different methods.; Other Names: Individualized nutritionnal intervention; Nutritionnal counselling
Active Comparator: Nutrition + Semaglutide; This arm will initiate a pharmacological intervention to treat obesity (Semaglutide) and will participate in an individualized nutritionnal approach.	Other: Diet; Participants receiving this intervention will be seeing a registered dietician at each visit. The individualized approach will be based on recent literature (mostly hypocaloric) by using different methods.; Other Names: Individualized nutritionnal intervention; Nutritionnal counselling; Drug: semaglutide; Participants receiving this intervention will be starting with a dose of semaglutide 0.25 mg. Physicians will follow Wegovy® Dosing Schedule guidelines, ending with a final dose of 2.4 mg at the fifth month. Type 2 diabetes participants wishing to stop at 1.0 mg will be allowed.
Active Comparator: Semaglutide; This arm will only initiate a pharmacological intervention to treat obesity (Semaglutide)	Drug: semaglutide; Participants receiving this intervention will be starting with a dose of semaglutide 0.25 mg. Physicians will follow Wegovy® Dosing Schedule guidelines, ending with a final dose of 2.4 mg at the fifth month. Type 2 diabetes participants wishing to stop at 1.0 mg will be allowed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver Steatosis	Transient elastography is an ultrasound-based modality that is non-invasive and measures the degree of steatosis with the controlled attenuation parameter (CAP; dB/m) and liver stiffness (kPa).This method will be used at each visit to follow the progression and the efficiency of the interventions. The following ranges will be use to classify hepatic steatosis based on CAP (dB/m) (specific to FibroScan®): S0 (< 302), S1 (302-331), S2 (331-337) and S3 (>337).	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
Liver Stiffness	Transient elastography is an ultrasound-based modality that is non-invasive and measures the degree of steatosis with the controlled attenuation parameter (CAP; dB/m) and liver stiffness (kPa).This method will be used at each visit to follow the progression and the efficiency of the interventions. The following ranges will be use to classify hepatic fibrosis based on liver stiffness (kPa) (specific to FibroScan®): F0-F1 (< 8.0), F2 (8.9-9.7), F3 (9.7-13.6) and F4 (>13.6).	From enrollment to the end of the clinical trial at 12 months (for 4 visits)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver function (biochemistry)	Blood samples will be drawn at each visit to assess the following measures: liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT], alkaline phosphatase [ALP]), total bilirubin and albumin. Liver scores will also be calculated: fatty liver index (FLI) and fibrosis-4 index (FIB-4) The following normal ranges will be used: AST : [8-33] U/L;; ALT : [10-40] U/L;; GGT : [2-30] U/L;; ALP : [30-120] U/L;; Total bilirubin : [5-21] umol/L;; Albumin : [35-30] g/L.; FLI : <30 : Low risk of hepatic steatosis ; >60 : High risk of hepatic steatosis.; FIB-4 : >3.48 : High risk of cirrhosis	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
Lipid panel	Blood samples will be drawn at each visit to assess the lipid panel. The following ranges will be used: triglycerides: < 1.5 mmol/L;; total cholesterol: < 5.20 mmol/L;; LDL-cholesterol: < 2.59 mmol/L;; HDL-cholesterol: > 1.55 mmol/L;	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
Change from Baseline in the gut microbiota diversity	The composition of the gut microbiota will be measured at each visit with the participants' stool samples. The difference between the concentration of gut microbiota diversity (bacteria, families, phyllum, etc.) will be analyzed.	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
Change from Baseline in blood lipids and metabolites	We will perform lipidomic and metabolomic measures with blood samples of each visit with liquid chromatography coupled with mass spectrometry (LC-MS/MS).	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
Glucose	Blood samples will be drawn at each visit to assess the glucose. The following range will be used: - glucose: < 5.6 mmol/L;	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
Insulin	Blood samples will be drawn at each visit to assess insulin The following range will be used: - insuline: [20-60] pmol/L;	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
Glycated hemoglobin	Blood samples will be drawn at each visit to assess HbA1c The following range will be used: - HbA1c: < 6.5 %;	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
C-reactive protein	Blood samples will be drawn at each visit to assess the c-reactive protein The following range will be used: - CRP: < 10 mg/L.	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
Liver enzymes	Blood samples will be drawn at each visit to assess the following measures: liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT] and alkaline phosphatase [ALP]), The following normal ranges will be used: AST : [8-33] U/L;; ALT : [10-40] U/L;; GGT : [2-30] U/L;; ALP : [30-120] U/L.	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
Fatty liver index (FLI)	The Fatty liver index (FLI) is a non-invasive score to calculate liver steatosis (using BMI, WC, TG and GGT). The following ranges will be used: <30 : Low risk of hepatic steatosis ;; >60 : High risk of hepatic steatosis.	From enrollment to the end of the clinical trial at 12 months (for 4 visits)
Fibrosis-4 index (FIB-4)	The fibrosis-4 index (FIB-4) is a non-invasive score to calculate liver fibrosis (using Age, AST, ALT and Platelet count). The following normal range will be used: - <30 : Low risk of hepatic steatosis ; >60 : High risk of hepatic steatosis. fatty liver index (FLI) and The following range will be used: - FIB-4 : >3.48 : High risk of cirrhosis	From enrollment to the end of the clinical trial at 12 months (for 4 visits)

Collaborators and Investigators

• Sponsor: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
• Investigators: Principal Investigator: Fannie Lajeunesse-Trempe, MD., Ph.D., Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: January 7, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 7, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Obesity; Microbiome; Semaglutide; Nutrition; Pharmacotherapy; Lipidomics; Transient elastography; Metabolic associated fatty liver disease; GLP-1 receptor analogs
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: 2025-4271

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No