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

NCT05369585 | Completed DMC

• 2 other identifiers: 2021-408255926
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Prediabetic State; Dysglycemia; Overweight and Obesity

Keywords

Dysglycemia; Prediabetes; Diabetes risk; Cardio-metabolic risk; Diet supplement; Plant extracts; Polyphenols; Microbiota; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (35)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• Evolution of metagenomic parameters (whole metagenome shotgun sequencing)

  Whole metagenome shotgun sequencing

  Baseline and V3 (8 weeks of intervention)

• Evolution of metagenomic parameters (microbiota diversity)

  Microbiota diversity measurements (Shannon index)

  Baseline and V3 (8 weeks of intervention)

• Evolution of metagenomic parameters (microbiota richness)

  Microbiota richness measurements (Simpson index)

  Baseline and V3 (8 weeks of intervention)

• Evolution of liver MRI

  Liver fat content

  Baseline and V3 (8 weeks of intervention)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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)

• 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 Outcomes (9)

• Evolution of Safety parameters (hepatic enzymes)

  Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)

• Evolution of Safety parameters (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)

• Evolution of Safety parameters (albumin)

  Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)

• Evolution of Safety parameters (creatinine)

  Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)

• Evolution of complete blood count (red and white blood cells, platelet)

  Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)

Study Arms (1)

TOTUM-63

EXPERIMENTAL

Experimental active are supplemented with TOTUM-63, taken 3 times per day.

Dietary Supplement: TOTUM-63

Interventions

TOTUM-63 DIETARY_SUPPLEMENT

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.

TOTUM-63

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 %

You may not qualify if:

• 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.

Sponsors & Collaborators

• Valbiotis: lead
• Laval University: collaborator
• Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec: collaborator
• Valbiotis Canada inc.: collaborator

Study Sites (1)

Institute of Nutrition and Funtional Foods (INAF) - Laval University

Québec, G1V 0A6, Canada

Location

MeSH Terms

Conditions

Prediabetic State; Overweight; Obesity

Interventions

TOTUM-63

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• André Marette, PhD

  Laval University

  PRINCIPAL INVESTIGATOR

• Patrick Couture, MD FRCP PhD

  Laval University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, single center, single arm

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: May 11, 2022
• Study Start: April 25, 2022
• Primary Completion: April 12, 2023
• Study Completion: April 12, 2023
• Last Updated: November 13, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)