Type 2 Diabetes Clinical Trial
— MICRODIETOfficial title:
Modulation of Protein Intake to Target Gut-microbiota Derived Metabolites of Amino Acids in Individuals With Type 2 Diabetes From Varying Ethnic Backgrounds
Verified date | September 2021 |
Source | Assistance Publique - Hôpitaux de Paris |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Context and justification: There is growing evidence that the gut microbiota is a key element in the pathophysiology of cardio-metabolic diseases (CMD) such as Type 2 Diabetes (T2D). One hypothesis is that gut-derived metabolites (from diet) have an important role in the host metabolism. Preliminary results show that imidazole propionate (ImP), a degradation product of the essential amino acid histidine, is produced by the gut microbiota of T2D patients, but not healthy subjects. The gut microbiota itself is strongly influenced by diet and ethnicity. However, most dietary intervention studies have focused on the role of fiber intake and the effect of dietary protein on the gut microbiota composition and metabolite production is not well known. Our hypothesis is that, depending on the baseline gut microbiome composition, a diminution in protein intake could decrease the microbial production of metabolites such as ImP and improve the metabolism of the host. We also hypothesize that the effects of such an intervention could depend the ethnic background. Objective: To study the effects of a high protein (HP) vs a low protein (LP) diet on gut microbiota composition and production of pro-diabetic metabolites in type 2 diabetes (T2D) patients from Caucasian and Caribbean ethnicity depending on baseline metagenomics richness. Study design: Randomized controlled three months dietary intervention study Study Population: T2D patients from Caucasian (N=80) and Caribbean (N=40) background who are on a stable dose of metformin and do not use insulin or proton-pump inhibitors. Intervention: Subjects will be randomized to either a high protein (HP) or low protein (LP) diet for three months. Individuals of Caucasian ethnicity, will also be stratified according to either a high or low gut microbiota gene richness. All subjects will receive pre-cooked meals 6 days per week and daily food packages. Subjects are required to keep food diaries three days a week and will also have weekly contact with an Pitié-Salpêtrière dietician. Outcome measures: Primary endpoint is the change in glycemic excursion (area under the curve) after a mixed meal test between baseline and 12 weeks after the beginning of the intervention. Furthermore, we will study oral and fecal microbiota composition changes as well as serum levels of intestinal metabolites, such as ImP, body weight and body composition at baseline and after 12 weeks. Sample Size: It is calculated that a total of 20 patients per arm are needed so 120 patients in total.
Status | Completed |
Enrollment | 65 |
Est. completion date | April 14, 2021 |
Est. primary completion date | April 14, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 40 Years to 70 Years |
Eligibility | Inclusion Criteria: 1. Age = 40 years and <70 years 2. 2. Type 2 Diabetic Subjects (T2D) 3. Treated with stable dose of metformin (no dose change in the last 3 months) 4. BMI = 25 kg / m2 5. Caucasian or Caribbean origin 6. Written and oral comprehension of the French language 7. Patient affiliated to health care. 8. Patient having been informed of the study and having given written consent to participation Exclusion Criteria: 1. Pregnancy or breastfeeding 2. Insulin treatment 3. HbA1c = 9% (<3 months) 4. Recent antibiotic treatment (<3 months) 5. Recent treatment with proton pump inhibitor (<3 months) 6. Food allergies or documented intolerances 7. Patient not willing to eat the foods provided in the protocol 8. Neuromuscular or neurological disease 9. History of digestive cancer and / or abdominal radiotherapy 10. History of gastrointestinal surgery with gastrointestinal resection 11. Acute or chronic inflammatory or infectious disease (including HIV, HCV, HBV) 12. Organ Transplantation, Immunosuppressive drugs 13. Severe chronic renal insufficiency (creatinine> 150 µmol / l or eDFG <50 ml / min per 1.73 m2 body surface area) 14. Patient currently included in an interventional clinical study (patients included in an observational study may be included) 15. Patient who received an experimental treatment in a research involving the human person in the last 2 months 16. Subject taking a dietary supplement (> 100kcal / d) 17. Subject with severe eating disorders (anorexia, bulimia, binge eating disorders, etc.) 18. History of bariatric surgery 19. Subject practicing an intense sport activity (more than 10 hours of sport per week) 20. Subject unwilling to maintain an alcohol consumption of less than 50g per week (eg 5 glasses of wine) and less than 10g per day (eg 1 glass of wine) 21. Patient under tutorship or curatorship |
Country | Name | City | State |
---|---|---|---|
France | Hôpital PITIE SALPETRIERE - APHP | Paris |
Lead Sponsor | Collaborator |
---|---|
Assistance Publique - Hôpitaux de Paris | ICAN Nutrition Education and Research |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Post meal tolerance test glycemic excursion (area under the curve) | After overnight fasting: Ingestion of 2x125ml de Fortimel® Compact (Nutricia) 600 kcal with 74g carbohydrates (50% of energy), 24g protein (16% of energy) et 23,2g fat (34% of energy). Blood glucose sampling à T0, 30, 60, 90, 120, 180, 240 min |
Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Post meal tolerance test insulin excursion (area under the curve) | After overnight fasting: Ingestion of 2x125ml de Fortimel® Compact (Nutricia) 600 kcal with 74g carbohydrates (50% of energy), 24g protein (16% of energy) et 23,2g fat (34% of energy). Blood glucose sampling à T0, 30, 60, 90, 120, 180, 240 min |
Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Matsuda index (from post meal tolerance test glucose and insulin levels) | After overnight fasting: Ingestion of 2x125ml de Fortimel® Compact (Nutricia) 600 kcal with 74g carbohydrates (50% of energy), 24g protein (16% of energy) et 23,2g fat (34% of energy). Blood glucose sampling à T0, 30, 60, 90, 120, 180, 240 min |
Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Insulinogenic index (from post meal tolerance test glucose and insulin levels) | After overnight fasting: Ingestion of 2x125ml de Fortimel® Compact (Nutricia) 600 kcal with 74g carbohydrates (50% of energy), 24g protein (16% of energy) et 23,2g fat (34% of energy). Blood glucose sampling à T0, 30, 60, 90, 120, 180, 240 min |
Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Disposition index (kahn) (from post meal tolerance test glucose and insulin levels) | After overnight fasting: Ingestion of 2x125ml de Fortimel® Compact (Nutricia) 600 kcal with 74g carbohydrates (50% of energy), 24g protein (16% of energy) et 23,2g fat (34% of energy). Blood glucose sampling à T0, 30, 60, 90, 120, 180, 240 min |
Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Serum concentration of glycated hemoglobin (HbA1c) | After overnight fasting | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Fasting concentration of glucose | After overnight fasting | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Insulin resistance index : HOMA 2 IR (based on fasting glucose and insulin concentration) | Fasting | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Insulin secretion index: HOMA 2 B (based on fasting glucose and insulin concentration) | Fasting | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | One week postprandial glucose excursions measured by continuous glucose monitoring sensors (CGMS) | Freestyle libre (Abbott) sensors placed for one week with continuous glucose monitoring | Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention | |
Secondary | Weight (kg) | Measured with same scale | Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention | |
Secondary | Waist circumference (cm) | Measured standing with a GULICK meter | Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention | |
Secondary | Sagittal diameter (cm) | Measured lying down with measuring rod | Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention | |
Secondary | Fat mass (DXA) | Measured by Dual-energy X-ray absorptiometry (DXA) | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Fat free mass (DXA) | Measured by Dual-energy X-ray absorptiometry (DXA) | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Visceral fat mass (DXA) | Measured by Dual-energy X-ray absorptiometry (DXA) | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Fat mass (BIA) | Measured by Body impedance analysis (Tanita scale) | Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention | |
Secondary | Fat free mass (BIA) | Measured by Body impedance analysis (Tanita scale)aspiration on a subgroup of patients | Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention | |
Secondary | Fasting concentration of Alanine transaminase (ALT) | After overnight fast | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Fasting concentration of Aspartate transaminase (AST) | After overnight fast | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Concentration of total cholesterol | After overnight fast | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Concentration of LDL cholesterol | After overnight fast | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Concentration of HDL cholesterol | After overnight fast | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Concentration of triglycerides | After overnight fast | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Gut microbiota changes | Shotgun metagenomic sequencing of DNA extracted from stool and saliva samples. | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Oral microbiota changes | Shotgun metagenomic sequencing of DNA extracted from stool and saliva samples. | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Concentration of Imidazole propionate | Targeted metabolomics | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Concentration of Trimethyl amine oxide (TMAO) | Targeted metabolomics | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Concentration of p cresol | Targeted metabolomics | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Concentration of indoxyl sulfate | Targeted metabolomics | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Concentration of C reactive protein (CRP) | Fasting serum levels measures | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Urinary urea excretion | 24h urinary sample measure | Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention | |
Secondary | SF 36 score (short form 36 quality of life questionnaire) | SF-36 questionnaire | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | General self efficacy scale score (GSES questionnaire) | GSES questionnaire | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Patient health questionnaire 9 score (PHQ-9 questionnaire) | PHQ-9 questionnaire | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Gastro-intestinal discomfort changes | Rome IV criteria | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Resting energy expenditure changes | Indirect calorimetry (Cosmed Quark RMR) | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Epigenetic modifications | On serum isolated monocytes for a subgroup of patients | Change between baseline (T0) and the end of the intervention (T12 weeks) | |
Secondary | Adipose tissue gene expression modifications | RNA sequencing of RNA extracted from adipose tissue obtained from adipose tissue aspiration on a subgroup of patients | Change between baseline (T0) and the end of the intervention (T12 weeks) |
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