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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Valbiotis
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Evolution of body mass index
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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 %
排除标准
- •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.
结局指标
主要结局
Evolution of body mass index
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Body mass index (in kg/m2)
Evolution of weight
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Weight (in kg)
Evolution of blood lipid profile (oxidized-LDL)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Oxidized-LDL (in ng/ml)
Evolution of metagenomic parameters (microbiota richness)
时间窗: Baseline and V3 (8 weeks of intervention)
Microbiota richness measurements (Simpson index)
Evolution of energy metabolism (respiratory quotient)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Evaluation of respiratory quotient before and after a 6-hours mixed-meal tolerance test (in carbon dioxide (CO2) eliminated / dioxygen (O2) consumed)
Evolution of fasting glycemia
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Fasting glycemia (in mmol/L)
Evolution of blood pressure
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Systolic blood pressure, diastolic blood pressure (in mmHg)
Evolution of insulin secretion
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Fasting insulinemia and C-peptide (in pmol/L)
Evolution of satiety hormones
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Peptide tyrosine tyrosine (PYY), cholecystokinin (in pg/ml)
Evolution of inflammatory response (fibrinogen)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Fibrinogen (in ng/ml)
Evolution of metagenomic parameters (microbiota diversity)
时间窗: Baseline and V3 (8 weeks of intervention)
Microbiota diversity measurements (Shannon index)
Evolution of NAFLD fibrosis score
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
NAFLD fibrosis score (\< -1.455 low fibrosis probability; -1.455 to 0.676 intermediate score; \> 0.676 high probability of fibrosis)
Evolution in kinetics of blood lipid profile
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Evaluation of triglycerides, total cholesterol, HDL-C, non-HDL-C and LDL-C during a 6-hours mixed-meal tolerance test (in mmol/L)
Evolution of heart rate
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Heart rate (in BPM)
Evolution of waist circumference
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Waist circumference (in cm)
Evolution of HbA1c
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Fasting HbA1c (in %)
Evolution of incretin response
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 (in pg/ml)
Evolution of blood lipid profile (ketones)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Ketones (in umol/L)
Evolution of fecal and plasma bile acid profiles
时间窗: Baseline and V3 (8 weeks of intervention)
Primary and secondary bile acids profiles (fecal and plasma) (in uM)
Evolution of metagenomic parameters (whole metagenome shotgun sequencing)
时间窗: Baseline and V3 (8 weeks of intervention)
Whole metagenome shotgun sequencing
Evolution in kinetics of glucose metabolism
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Evaluation of glucose concentrations during a 6-hours mixed-meal tolerance test (in mmol/L)
Evolution of inflammatory parameters (IL6, TNFA)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Evaluation of interleukin 6, tumour necrosis factor alpha before and after a 6-hours mixed-meal tolerance test (in pg/ml)
Evolution of energy metabolism (resting metabolic rate)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Evaluation of resting metabolic rate before and after a 6-hours mixed-meal tolerance test (in kcal/day)
Evolution of inflammatory response (hs-CRP)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
High-sensitivity C-reactive protein (in mg/L)
Evolution of blood lipid profile (lipid profile)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Triglycerides, total cholesterol, HDL-C, non-HDL-C, LDL-C, free-fatty-acids (in mmol/L)
Evolution of liver MRI
时间窗: Baseline and V3 (8 weeks of intervention)
Liver fat content
Evolution of FIB-4 index
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
FIB-4 index (FIB-4 index \< 1.45 in the context of steatosis allows the exclusion of a clinically significant fibrosis)
Evolution of BARD score
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
BARD score (from 0 to 4, with a score of 4 resulting in a higher risk of advanced fibrosis)
Evolution of adipokines
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Adiponectin, leptin, plasminogen activator inhibitor 1 (in ng/ml)
Evolution of inflammatory response (IL6, TNFa)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Interleukin 6, tumour necrosis factor alpha (in pg/ml)
Evolution in kinetics of insulin secretion
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Evaluation of blood insulin and C-peptide during a 6-hours mixed-meal tolerance test (in pmol/L)
Evolution of inflammatory parameters (hs-CRP)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Evaluation high-sensitivity C-reactive protein before and after a 6-hours mixed-meal tolerance test (in mg/L)
Evolution of kinetics of incretin parameters
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Evaluation of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 during a 2-hours mixed-meal tolerance test (in pg/ml)
Evolution of inflammatory parameters (fibrinogen)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Evaluation of fibrinogen before and after a 6-hours mixed-meal tolerance test (in ng/ml)
Evolution of energy metabolism (energy expenditure)
时间窗: Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up)
Evaluation of energy expenditure before and after a 6-hours mixed-meal tolerance test (in kcal/kg/h)
次要结局
- Evolution of complete blood count (hematocrit)(Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up))
- Evolution of transcriptomics(Baseline and V3 (8 weeks of intervention))
- 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 (hemoglobin)(Baseline, V2 (4 weeks of intervention), V3 (8 weeks of intervention) and V4 (8 weeks of intervention + 4 weeks of follow-up))
- Evolution of metabolomics (amino acids, fatty acids and acylcarnitine species)(Baseline and V3 (8 weeks of intervention))
- 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))
- 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))