Clinical trial NCT05369585: Mode of Action (MoA) Study of TOTUM-63 in Individuals at Increased Cardio-metabolic Risk
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prediabetic State
Dysglycemia
Overweight and Obesity
Keywords: Dysglycemia
Prediabetes
Diabetes risk
Cardio-metabolic risk
Diet supplement
Plant extracts
Polyphenols
Microbiota
Magnetic Resonance Imaging
Lead sponsor: Valbiotis
Sponsor class: INDUSTRY
Collaborators: name: Laval University
name: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
name: Valbiotis Canada inc.
First posted: 2022-05-11
Enrollment: 20
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, single center, single arm
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Evolution of blood pressure
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of heart rate
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of weight
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of waist circumference
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of body mass index
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of fasting glycemia
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of insulin secretion
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of HbA1c
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of satiety hormones
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of adipokines
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of inflammatory response (fibrinogen)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of inflammatory response (IL6, TNFa)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of inflammatory response (hs-CRP)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of incretin response
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of blood lipid profile (lipid profile)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of blood lipid profile (oxidized-LDL)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of blood lipid profile (ketones)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of fecal and plasma bile acid profiles
timeFrame: Baseline and V3 (8 weeks of intervention)
measure: Evolution of metagenomic parameters (whole metagenome shotgun sequencing)
timeFrame: Baseline and V3 (8 weeks of intervention)
measure: Evolution of metagenomic parameters (microbiota diversity)
timeFrame: Baseline and V3 (8 weeks of intervention)
measure: Evolution of metagenomic parameters (microbiota richness)
timeFrame: Baseline and V3 (8 weeks of intervention)
measure: Evolution of liver MRI
timeFrame: Baseline and V3 (8 weeks of intervention)
measure: Evolution of FIB-4 index
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of BARD score
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of NAFLD fibrosis score
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution in kinetics of glucose metabolism
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution in kinetics of insulin secretion
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution in kinetics of blood lipid profile
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of kinetics of incretin parameters
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of inflammatory parameters (fibrinogen)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of inflammatory parameters (IL6, TNFA)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of inflammatory parameters (hs-CRP)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of energy metabolism (respiratory quotient)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of energy metabolism (resting metabolic rate)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of energy metabolism (energy expenditure)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Secondary outcomes:
measure: Evolution of Safety parameters (hepatic enzymes)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of Safety parameters (AST/ALT ratio)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of Safety parameters (albumin)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of Safety parameters (creatinine)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of complete blood count (red and white blood cells, platelet)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of complete blood count (hemoglobin)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of complete blood count (hematocrit)
timeFrame: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
measure: Evolution of transcriptomics
timeFrame: Baseline and V3 (8 weeks of intervention)
measure: Evolution of metabolomics (amino acids, fatty acids and acylcarnitine species)
timeFrame: Baseline and V3 (8 weeks of intervention)
Other outcomes:
Locations:
city: Quebec
country: Canada
facility: Institute of Nutrition and Funtional Foods (INAF) - Laval University
Study officials:
affiliation: Laval University
name: André Marette, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Laval University
name: Patrick Couture, MD FRCP PhD
role: PRINCIPAL_INVESTIGATOR
References: