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

Not Applicable

Not yet recruiting

• Conditions: Metabolic Associated Fatty Liver Disease; Metabolic Associated-dysfunction Steatohepatitis (MASH); Obesity
• Interventions: Other: Diet; Drug: semaglutide

• Registration Number: NCT06764056
• Lead Sponsor: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Brief Summary

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.

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 Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-18
• Study Start: 2025-01
• Study First Submitted QC: 2025-01-07
• Last Update Submitted: 2025-01-07
• Study First Posted: 2025-01-08
• Last Update Posted: 2025-01-08
• Primary Completion: 2026-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 120

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nutrition	Diet	This arm will only participate in an individualized nutritionnal approach.
Nutrition + Semaglutide	semaglutide	This arm will initiate a pharmacological intervention to treat obesity (Semaglutide) and will participate in an individualized nutritionnal approach.
Nutrition + Semaglutide	Diet	This arm will initiate a pharmacological intervention to treat obesity (Semaglutide) and will participate in an individualized nutritionnal approach.
Semaglutide	semaglutide	This arm will only initiate a pharmacological intervention to treat obesity (Semaglutide)

Primary Outcome Measures

Name	Time	Method
Liver Steatosis	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	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).
Liver Stiffness	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	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).

Secondary Outcome Measures

Name	Time	Method
Liver function (biochemistry)	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	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
Lipid panel	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	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;
Change from Baseline in the gut microbiota diversity	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	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.
Change from Baseline in blood lipids and metabolites	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	We will perform lipidomic and metabolomic measures with blood samples of each visit with liquid chromatography coupled with mass spectrometry (LC-MS/MS).
Glucose	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	Blood samples will be drawn at each visit to assess the glucose.; The following range will be used: - glucose: \< 5.6 mmol/L;
Insulin	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	Blood samples will be drawn at each visit to assess insulin; The following range will be used: - insuline: \[20-60\] pmol/L;
Glycated hemoglobin	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	Blood samples will be drawn at each visit to assess HbA1c; The following range will be used: - HbA1c: \< 6.5 %;
C-reactive protein	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	Blood samples will be drawn at each visit to assess the c-reactive protein; The following range will be used: - CRP: \< 10 mg/L.
Liver enzymes	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	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.
Fatty liver index (FLI)	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	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.
Fibrosis-4 index (FIB-4)	From enrollment to the end of the clinical trial at 12 months (for 4 visits)	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

Trial Locations

Locations (1)

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval; 🇨🇦 Québec, Quebec, Canada