Effects of TOTUM-448 on Liver Fat Content, Cardiometabolic Risk Factors and Gut Microbiota Among Participants with MASLD (CARDIO-LIVER)

A Parallel, Randomized, Placebo-Controlled, Double-Blinded Clinical Trial of the Effects of TOTUM-448 on Liver Fat Content, Cardiometabolic Risk Factors and Gut Microbiota Among Both Men and Women with MASLD

This clinical trial aims to investigate the effects of TOTUM-448, a mix of 5 plant extracts and choline, consumed at the daily regimen of two times per day, on liver fat content, cardiometabolic risk factors and gut microbiota among both men and women with MASLD.

Study Overview

• Status: Recruiting
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: TOTUM-448; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Véronique Sapone, MSc; Phone Number: +33 (0)6 75 32 66 59; Email: veronique.sapone@valbiotis.com

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 0A6
      • Recruiting
      • Institut sur la nutrition et les aliments fonctionnels (INAF)
      • Contact: Julie Marois, MSc; Phone Number: 405764 +1 (418) 656-2131; Email: julie.marois@fsaa.ulaval.ca
      • Contact: Patrick Couture, MD FRCP PhD
      • Contact: Marie-Claude Vohl, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Main Inclusion Criteria:

• Men and women aged between 18 and 75 years (including ranges);
• CAP Score ≥288dB/m with liver stiffness results <8kPa (corresponding to F0 to F1 fibrosis score) assessed by Fibroscan®;
• BMI ≥25 and <40 kg/m2 and WC thresholds according to the NAFLD Nomenclature consensus group (Rinella. 2023. Hepatology);
• Weight stable within ± 5% in the last three months.

Main Exclusion Criteria:

• Contraindications to MRI, Fibroscan® and DEXA;
• Suffering from a metabolic disorder susceptible to significantly affect glucose metabolism or plasma lipid levels or that might affect the study outcomes according to the investigator;
• Suffering from an uncontrolled arterial hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg);
• With a history of atherosclerotic cardiovascular disease (ASCVD);
• Taking medication which may affect the study outcomes;
• Alcohol consumption over ≥10 drinks/week for women and ≥15 drinks/week for men (women consuming more than 3 drinks/day and men consuming more than 4 drinks/day will also be excluded) or not agreeing to keep their alcohol consumption habits unchanged throughout the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TOTUM-448; The experimental active arm will be supplemented with TOTUM-448 twice per day.	Dietary supplement: TOTUM-448; 16 weeks of TOTUM-448 supplementation (4.284g/day corresponding to 8 capsules per day)
Placebo Comparator: Placebo; The placebo comparator arm will be supplemented with a placebo twice per day.	Dietary supplement: Placebo; 16 weeks of placebo supplementation (8 capsules per day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of liver fat content	Liver fat content measured by MRI	Baseline (V1) and End of supplementation after 16 weeks of supplementation (V3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of lipid profile	Measurement of standard lipid profile	Baseline (V1), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of glucose homeostasis	Measurement of glucose homeostasis	Baseline (V1), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of liver health	Cap score assessed by Fibroscan	Screening (V0), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of inflammation	Measurement of hs-CRP in mg /L Measurement of IL-6, MCP-1, RANTES in pg/ml	Baseline (V1), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of anthropometric variables	Measurement of BMI in kg/m²	Baseline (V1), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of body composition	Evolution of body composition (i.e. total and trunk fat mass, total and trunk lean body mass) measured by Dual Energy X-ray Absorptiometry (DEXA)	Baseline (V1) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of health-related quality of life	Health-related quality of life (HRQoF) assessed by Medical Outcome Study Short Form - 36 (MOS SF-36), a generic tool to measure and compare the HRQoL on study population.	Baseline (V1) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of hepatic function	Measurement of liver assessment	Screening (V0), Baseline (V1), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of kidney function	Measurement of kidney assessment	Screening (V0), Baseline (V1), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of hemodynamic measurements	Measurement of systolic and diastolic blood pressure in mmHg	Screening (V0), Baseline (V1), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of complete blood count	Measurement of white blood cells, red blood cells, number of platelets, amount of hemoglobin in the blood, hematocrit, mean red blood volume, mean hemoglobin amount per red blood cell, mean amount of hemoglobin relative to the size of the cell per red blood cell	Screening (V0), Baseline (V1), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of thyroid stimulating hormone	Measurement of thyroid stimulating hormone	Screening (V0), Baseline (V1), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)
Evolution of adverse events (TEAE, STEAE, TEAE leading to investigational product discontinuation, TEAR)	Treatment-Emergent Adverse Events (TEAE), Serious-TEAE (STEAE), TEAE leading to investigational product discontinuation, Treatment-Emergent Adverse Reaction (TEAR)	Screening (V0), Baseline (V1), Following 8 weeks of supplementation (V2) and End of supplementation after 16 weeks of supplementation (V3)

Collaborators and Investigators

• Sponsor: Valbiotis
• Collaborators: CHU de Quebec-Universite Laval; Laval University; Institut universitaire de cardiologie et de pneumologie de Québec, University Laval; Valbiotis Canada inc.
• Investigators: Principal Investigator: André Marette, PhD, Laval University

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 12, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Estimated): November 26, 2024

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Obesity; Dietary supplement; Overweight; Body composition; Magnetic Resonance Imaging; Insulin sensitivity; Oral glucose tolerance test; Polyphenols; Plant extracts; Glucose metabolism; Cardiometabolic risk factors; Liver function; Insulin secretion; Fibroscan; Liver fat content; MASLD; Health-related quality of Life
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 2022-497

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