Mode of Action (MoA) Study of TOTUM-63 in Individuals at Increased Cardio-metabolic Risk

An Open-label, Single Arm, Clinical Trial to Explore the Consumption Effects of TOTUM-63 on Metabolic Signatures, Microbiome, Energy Metabolism and Post-prandial Nutrient Processing in Individuals at Increased Cardio-metabolic Risk

This clinical study aims to investigate the effects of TOTUM-63, a mix of 5 plant extracts, consumed at the daily regimen of three times per day, on cardiometabolic health and gut microbiota profile in overweight-obese individuals.

In 2019, over 460 million adults had diabetes worldwide. Moreover, it was estimated by the International Diabetes Federation that about 700 million adults will have type 2 diabetes (T2D) by 2045. Valbiotis is a research & development company dedicated to scientific innovation for preventing and reducing the risk of metabolic and cardiovascular disease (CVD) using specific combinations of plant-based molecules. Valbiotis developed a formula (TOTUM-63) which is composed by the association of five plant extracts.

Given the results obtained in pre-clinical studies, as well as the good tolerance and first efficacy results of TOTUM-63 in two clinical trials on human subjects, this research aims to investigate the effects of TOTUM-63 on cardiometabolic health and gut microbiota profile in overweight-obese individuals. TOTUM-63 will be tested (5g acutely and 5g/d over 8 weeks of supplementation) on energy metabolism, post-prandial nutrients metabolism and hepatic health in overweight and obese subjects. Blood and feces samples collected before, and after the supplementation will allow to perform metabolomic, transcriptomic and metagenomics analyses to further explore the potential mechanisms of action of TOTUM-63.

Main Inclusion Criteria:

• Body mass index (BMI) between ≥ 27 and < 40 kg/m2 kg/m²;
• Waist circumference > 94 cm for men and > 80 cm for women;
• Weight stable within ± 5% in the last three months;
• Fasting plasma TG ≥ 1.35 OR fasting glycemia ≥ 5.6 and ≤ 6.9 mmol/L OR HbA1c ≥ 5.6 and ≤ 6.4 %

Main Exclusion Criteria:

• Any metabolic disorder requiring pharmacological treatment and susceptible to affect glucose metabolism or plasma lipid levels or that might affect the study outcomes according to the investigator;
• Taking medication which may affect the study outcomes (or a medication modification less than 3 months prior to the study);
• To have taken regularly natural health products or enriched foods susceptible to modify the parameters followed by the investigator within the 3 months prior to the study;
• With a known or suspected food allergy, intolerance or hypersensitivity to any of the study products' ingredient as well as the non-medicinal ingredients of the product;
• Consuming more than 4 drinks of alcohol per week;
• Having a lifestyle deemed incompatible with the study according to the investigator including high level of physical activity (defined as more than 10 hours of intense physical activity a week, walking excluded);
• Pregnant or lactating women or intending to become pregnant within the timeframe of the study;
• Fasting blood triglycerides (TG) > 2.5 mmol/L;
• Fasting blood LDL-C > 4.9mmol/L or non-HDL-C > 5.7 mmol/L;
• Blood AST ≥ 45 U/L for men; and blood AST ≥ 35 U/L for women;
• Blood ALT ≥ 60 U/L for men; and blood ALT ≥ 50 U/L for women;
• Blood GGT ≥ 75 U/L for men; and blood GGT ≥ 50 U/L for women;
• Blood creatinine concentration > 125 μmol/L AND Estimated Glomerular Filtration Rate (eGFR) (calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) < 60 mL/min/1.73m²;
• Complete blood count (CBC) with hemoglobin < 120 g/L or leucocytes < 3000 /mm3 or leucocytes > 16000 /mm3 or clinically significant abnormality according to the investigator.