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

Overweight and Obesity Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05369585
• Other study ID #: 2021-408
• Secondary ID: 2559262021-408
• Status: Completed
• Phase: N/A
• Start date: April 25, 2022
• Est. completion date: April 12, 2023

Study information

• Verified date: May 2022
• Source: Valbiotis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 12, 2023
• Est. primary completion date: April 12, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dysglycemia
• Overweight
• Overweight and Obesity
• Prediabetic State

Intervention

Dietary Supplement:
• TOTUM-63
5-g per day dose of TOTUM-63 supplement, a mix of 5 plant extracts. Daily dose for 8 weeks followed by a 4 weeks follow-up period without supplementation.

Locations

Country	Name	City	State
Canada	Institute of Nutrition and Funtional Foods (INAF) - Laval University	Quebec

Sponsors (4)

Lead Sponsor	Collaborator
Valbiotis	Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Laval University, Valbiotis Canada inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evolution of blood pressure	Systolic blood pressure, diastolic blood pressure (in mmHg)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of heart rate	Heart rate (in BPM)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of weight	Weight (in kg)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of waist circumference	Waist circumference (in cm)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of body mass index	Body mass index (in kg/m2)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of fasting glycemia	Fasting glycemia (in mmol/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of insulin secretion	Fasting insulinemia and C-peptide (in pmol/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of HbA1c	Fasting HbA1c (in %)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of satiety hormones	Peptide tyrosine tyrosine (PYY), cholecystokinin (in pg/ml)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of adipokines	Adiponectin, leptin, plasminogen activator inhibitor 1 (in ng/ml)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of inflammatory response (fibrinogen)	Fibrinogen (in ng/ml)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of inflammatory response (IL6, TNFa)	Interleukin 6, tumour necrosis factor alpha (in pg/ml)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of inflammatory response (hs-CRP)	High-sensitivity C-reactive protein (in mg/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of incretin response	Glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 (in pg/ml)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of blood lipid profile (lipid profile)	Triglycerides, total cholesterol, HDL-C, non-HDL-C, LDL-C, free-fatty-acids (in mmol/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of blood lipid profile (oxidized-LDL)	Oxidized-LDL (in ng/ml)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of blood lipid profile (ketones)	Ketones (in umol/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of fecal and plasma bile acid profiles	Primary and secondary bile acids profiles (fecal and plasma) (in uM)	Baseline and V3 (8 weeks of intervention)
Primary	Evolution of metagenomic parameters (whole metagenome shotgun sequencing)	Whole metagenome shotgun sequencing	Baseline and V3 (8 weeks of intervention)
Primary	Evolution of metagenomic parameters (microbiota diversity)	Microbiota diversity measurements (Shannon index)	Baseline and V3 (8 weeks of intervention)
Primary	Evolution of metagenomic parameters (microbiota richness)	Microbiota richness measurements (Simpson index)	Baseline and V3 (8 weeks of intervention)
Primary	Evolution of liver MRI	Liver fat content	Baseline and V3 (8 weeks of intervention)
Primary	Evolution of FIB-4 index	FIB-4 index (FIB-4 index < 1.45 in the context of steatosis allows the exclusion of a clinically significant fibrosis)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of BARD score	BARD score (from 0 to 4, with a score of 4 resulting in a higher risk of advanced fibrosis)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of NAFLD fibrosis score	NAFLD fibrosis score (< -1.455 low fibrosis probability; -1.455 to 0.676 intermediate score; > 0.676 high probability of fibrosis)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution in kinetics of glucose metabolism	Evaluation of glucose concentrations during a 6-hours mixed-meal tolerance test (in mmol/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution in kinetics of insulin secretion	Evaluation of blood insulin and C-peptide during a 6-hours mixed-meal tolerance test (in pmol/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution in kinetics of blood lipid profile	Evaluation of triglycerides, total cholesterol, HDL-C, non-HDL-C and LDL-C during a 6-hours mixed-meal tolerance test (in mmol/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of kinetics of incretin parameters	Evaluation of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 during a 2-hours mixed-meal tolerance test (in pg/ml)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of inflammatory parameters (fibrinogen)	Evaluation of fibrinogen before and after a 6-hours mixed-meal tolerance test (in ng/ml)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of inflammatory parameters (IL6, TNFA)	Evaluation of interleukin 6, tumour necrosis factor alpha before and after a 6-hours mixed-meal tolerance test (in pg/ml)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of inflammatory parameters (hs-CRP)	Evaluation high-sensitivity C-reactive protein before and after a 6-hours mixed-meal tolerance test (in mg/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of energy metabolism (respiratory quotient)	Evaluation of respiratory quotient before and after a 6-hours mixed-meal tolerance test (in carbon dioxide (CO2) eliminated / dioxygen (O2) consumed)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of energy metabolism (resting metabolic rate)	Evaluation of resting metabolic rate before and after a 6-hours mixed-meal tolerance test (in kcal/day)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Primary	Evolution of energy metabolism (energy expenditure)	Evaluation of energy expenditure before and after a 6-hours mixed-meal tolerance test (in kcal/kg/h)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Secondary	Evolution of Safety parameters (hepatic enzymes)	Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT) (in U/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Secondary	Evolution of Safety parameters (AST/ALT ratio)	AST/ALT ratio	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Secondary	Evolution of Safety parameters (albumin)	Albumin (in g/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Secondary	Evolution of Safety parameters (creatinine)	Creatinine (in umol/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Secondary	Evolution of complete blood count (red and white blood cells, platelet)	Red blood cells, white blood cells, platelet (in cells/mm3)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Secondary	Evolution of complete blood count (hemoglobin)	Hemoglobin (in g/L)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Secondary	Evolution of complete blood count (hematocrit)	Hematocrit (in %)	Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Secondary	Evolution of transcriptomics	RNA sequencing	Baseline and V3 (8 weeks of intervention)
Secondary	Evolution of metabolomics (amino acids, fatty acids and acylcarnitine species)	Evolution of amino acids, fatty acids and acylcarnitine species (in uM)	Baseline and V3 (8 weeks of intervention)