Study to Assess the Effects of Non Digestible Carbohydrates on Long-Term Glucose Homeostasis in Untreated Prediabetic Subjects

Study Overview
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Brief Summary
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This clinical study aims to prove that the efficacy of non digestible carbohydrates supplementation (daily dose of 20 grams consumed twice a day for 12 weeks) on the regulation of glucose homeostasis is superior than placebo in prediabetic subjects.

Official Title
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Randomized, Double-Blinded, Placebo-Controlled Study to Assess the Effects of Short-Chain Fructo-Oligosaccharides on Long-Term Glucose Homeostasis in Untreated Prediabetic Subjects

Conditions
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Pre Diabetes, Prediabetic State, Dysglycemia, PreDiabetes

Intervention / Treatment
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* Dietary Supplement: Non digestible carbohydrates
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 65 years (limits included); BMI between 25 and 34.9 kg/m² (limits included); Dysglycemic or prediabetic subjects with no antidiabetic medication (medical or lifestyle (hygiene-dietetic measures or specific regimen treatment); Consuming 10 to 20 g quantity of fiber per day (based on the 3-days food diary fulfilled by the subject between V1 and V2 visits); Non smoking subject and agreeing to keep this habit unchanged throughout the study; Able and willing to participate to the study by complying with the protocol procedures as evidenced by his dated and signed informed consent form; Affiliated with a social security scheme; Agree to be registered on the volunteers in biomedical research file; Fasting venous glycemia ≥ 1 g/L and ≤ 1.25 g/L at V1 visit. Exclusion Criteria: Metabolic disorder such as diabetes, uncontrolled thyroidal trouble or other metabolic disorder; Severe chronic disease or Intestinal Bowel Syndrome (IBS) or gastrointestinal disorders found to be inconsistent with the conduct of the study by the investigator; History of retinopathy, microalbuminuria, ischemic cardiovascular event in the 6 months before the study; Known or a suspected food allergy or intolerance orhypersensitivity to any food ingredient; Known or suspected food allergy or intolerance or hypersensitivity to any of the study products' ingredient; Pregnant or lactating women or intending to become pregnant within 4 months ahead; Women starting hormone replacement therapy or oral contraception (treatment must be stable for at least 3 months); History of bariatric surgery; History of any surgery in the 3 months before V1 visit or having scheduled any surgery within 4 months ahead; Under dietary supplement which could significantly affect parameter(s) followed during the study according to the investigator or stopped in a too short period before the V1 visit (< 3 months); Under treatment which could significantly affect parameter(s) followed during the study according to the investigator or stopped less than 3 months before the V1 visit; Under antibiotic treatment in the 3 to 6 months before V1 visit, depending on the antibiotic consumed and according to the investigator; Significant change in food habits or in physical activity in the 3 months before V1 visit or not agreeing to keep them unchanged throughout the study; Current or planned in the next 4 months specific diet (hyper or hypocaloric, vegan, vegetarian…) or stopped less than 3 months before the study; Personal history of anorexia nervosa, bulimia or significant eatingdisorders according to the investigator; Consuming more than 3 standard drinks of alcoholic beverage daily for men or 2 daily for women or not agreeing to keep his alcohol consumption habits unchanged throughout the study; Taking part in another clinical trial or being in the exclusion period of a previous clinical trial; Having received, during the last 12 months, indemnities for clinical trial higher or equal to 4500 Euros; Under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision; Psychological or linguistic incapability to sign the informed consent; Impossible to contact in case of emergency. Fasting blood triglycerides > 3,5 g/L; Fasting blood of total cholesterol > 4,5 g/L or HDLc < 0,1 g/L with an abnormality judged as clinically significant according to the investigator; Blood ASAT, ALAT or GGT > 3 times ULN (laboratory Upper Limit of Normal); Blood urea > 12 mmol/L or creatinine > 125 μmol/L; Complete Blood Count (CBC) with hemoglobin < 11 g/L or leucocytes < 3000/mm3 or leucocytes > 16000/mm3.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: multicentre randomized, parallel arms, double-blind, placebo-controlled clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test product<br>Food ingredient containing non digestible carbohydrates, in shape of powder | Dietary Supplement: Non digestible carbohydrates<br>* the subjects will consume 2 bags of 10 grams per day of the product: 1 bag in the morning and 1 bag at lunch or in the evening, at the beginning of the meal, diluted in a large glass of beverage, during 12 weeks.<br>|
| Placebo Comparator: Placebo<br>Food ingredient containing containing 95% of maltodextrin | Dietary Supplement: Placebo<br>* the subjects will consume 2 bags of 10 grams per day of the product: 1 bag in the morning and 1 bag at lunch or in the evening, at the beginning of the meal, diluted in a large glass of beverage, during 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycated hemoglobin | Change from baseline of Hba1c level (%) | V2 (randomization) and V5 (12 weeks of intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycated hemoglobin | Absolute variations of Hba1c level (%) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Fasting glycemia | Change from baseline of fasting glycemia (g/L) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Fasting insulinemia | Change from baseline of fasting insulinemia (mU/L) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Fructosamine | Change from baseline of fructosamine (μmol/L) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Insulin indexes | Change from baseline of HOMA-IR (Homeostasis Model Assessment of Insulin) and QUICKI (Quantitative Insulin sensitivity Check Index) indices | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Insulin sensitivity index | Change from baseline of insulin sensitivity index (ISI) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Glycemia level | Change from baseline of glycemia level (g/L) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Incremental Area Under the Curve (iAUC) of glycemia | Change from baseline of iAUC of glycemia (g/L) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Insulinemia | Change from baseline of insulinemia levels (mU/L) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Incremental Area Under the Curve (iAUC) of insulinemia | Change from baseline of iAUC of insulinemia (mU/L) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Glucacon-like Peptide 1 (GLP-1) | Change from baseline of GLP-1 levels (pmol/L) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Bone mineral composition | Change from baseline of bone mineral composition (kg) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Total lean mass | Change from baseline of total lean mass (g and %) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Total fat mass | Change from baseline of total fat mass (g and %) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Bone Mineral Density | Change from baseline of bone mineral density (g/cm2) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Total Body Mass | Change from baseline of total body mass (kg) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Weight | Change from baseline of weight (in kg) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Body Mass Index (BMI) | Change from baseline of BMI (in kg/m2) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Waist and Hip measurement | Change from baseline of waist and hip Circumference (in cm) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Anthropometric ratios | Change from baseline of Waist to Hip ratio and Waist to Height ratio | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Satiety and Appetite sensation | Change on satiety and appetite sensation using 100-mm VAS to complete 15 min before the meal, 30 min, 60 min, 120 min, 180 min and 240 min after the meal at which study product was consumed | V2 (randomization) and V5 (12 weeks of intervention) | 
| Total energy intake | Change from baseline of total energy intake - TEI (kcal/day) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Energy intake | Change from baseline of percentage of energy intake from fat, carbohydrates and protein (g and %TEI) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Fiber intake | Change from baseline of percentage of percentage of fiber (g) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Alcohol intake | Change from baseline of percentage of percentage of alcohol intake (absolute quantities, g/day) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Biomarker of inflammation | Change from baseline of high-sensitivity C-reactive Protein (CRPhs) (mg/L) | V2 (randomization), V3 (4 weeks of intervention), V4 (8 weeks of intervention) and V5 (12 weeks of intervention) | 
| Intestinal microbiota composition | Change from baseline microbiota composition for alpha-diversity indices (Shannon and Chao indices) and abundances at the phylum, family and genus level assessed by 16S metabarcoding (in a subgroup of 30 subjects only) | V2 (randomization) and V5 (12 weeks of intervention) | 
| Fecal Short-Chain Fatty Acids (SCFA) | Change from baseline of fermentative activity of the intestinal microbiota assessed by measuring short-chain fatty acids concentrations in stool (in the same subgroup of 30 subjects only) | V2 (randomization) and V5 (12 weeks of intervention) |