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Trial record 28 of 751 for:    Area Under Curve AND meal

The Interaction Between Protein Intake, Gut Microbiota and Type 2 Diabetes in Subjects With Different Ethnic Backgrounds (MICRODIET)

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ClinicalTrials.gov Identifier: NCT03732690
Recruitment Status : Recruiting
First Posted : November 7, 2018
Last Update Posted : April 29, 2019
Sponsor:
Collaborator:
ICAN Nutrition Education and Research
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Other: Diet HP Other: Diet LP Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Modulation of Protein Intake to Target Gut-microbiota Derived Metabolites of Amino Acids in Individuals With Type 2 Diabetes From Varying Ethnic Backgrounds
Actual Study Start Date : December 5, 2018
Estimated Primary Completion Date : June 5, 2020
Estimated Study Completion Date : January 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Diet High Protein (HP)
Diet High Protein (HP) : 30% protein, 40% carbohydrate and 30% fat
Other: Diet HP

2000kcal for men 1800 kcal for women. Food boxes (HP pre-cooked meals and meat/chicken/fish portions, HP breads and snacks) will be provided to the participants throughout the study reaching 40-50% of their prescribed daily energy intake for 6 days per week. In total 932 kcal are provided through this food boxes (54g of carbohydrate, 101g of protein, 34,6g of fat). The rest of the daily food intake will be guided by a dietician with a list of recommended high protein foods.

Subjects are required to keep food diaries three days a week and will also have weekly contact with a dietician.


Diet Low Protein (LP)
Diet Low Protein (LP) : 10% protein, 55% carbohydrate and 35% fat
Other: Diet LP
2000kcal for men 1800 kcal for women. Food boxes (LP pre-cooked meals, LP breads and snacks) will be provided to the participants throughout the study




Primary Outcome Measures :
  1. Post meal tolerance test glycemic excursion (area under the curve) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]

    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



Secondary Outcome Measures :
  1. Post meal tolerance test insulin excursion (area under the curve) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]

    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


  2. Matsuda index (from post meal tolerance test glucose and insulin levels) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]

    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


  3. Insulinogenic index (from post meal tolerance test glucose and insulin levels) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]

    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


  4. Disposition index (kahn) (from post meal tolerance test glucose and insulin levels) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]

    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


  5. Serum concentration of glycated hemoglobin (HbA1c) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    After overnight fasting

  6. Fasting concentration of glucose [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    After overnight fasting

  7. Insulin resistance index : HOMA 2 IR (based on fasting glucose and insulin concentration) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Fasting

  8. Insulin secretion index: HOMA 2 B (based on fasting glucose and insulin concentration) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Fasting

  9. One week postprandial glucose excursions measured by continuous glucose monitoring sensors (CGMS) [ Time Frame: Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention ]
    Freestyle libre (Abbott) sensors placed for one week with continuous glucose monitoring

  10. Weight (kg) [ Time Frame: Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention ]
    Measured with same scale

  11. Waist circumference (cm) [ Time Frame: Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention ]
    Measured standing with a GULICK meter

  12. Sagittal diameter (cm) [ Time Frame: Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention ]
    Measured lying down with measuring rod

  13. Fat mass (DXA) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Measured by Dual-energy X-ray absorptiometry (DXA)

  14. Fat free mass (DXA) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Measured by Dual-energy X-ray absorptiometry (DXA)

  15. Visceral fat mass (DXA) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Measured by Dual-energy X-ray absorptiometry (DXA)

  16. Fat mass (BIA) [ Time Frame: Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention ]
    Measured by Body impedance analysis (Tanita scale)

  17. Fat free mass (BIA) [ Time Frame: Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention ]
    Measured by Body impedance analysis (Tanita scale)aspiration on a subgroup of patients

  18. Fasting concentration of Alanine transaminase (ALT) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    After overnight fast

  19. Fasting concentration of Aspartate transaminase (AST) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    After overnight fast

  20. Concentration of total cholesterol [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    After overnight fast

  21. Concentration of LDL cholesterol [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    After overnight fast

  22. Concentration of HDL cholesterol [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    After overnight fast

  23. Concentration of triglycerides [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    After overnight fast

  24. Gut microbiota changes [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Shotgun metagenomic sequencing of DNA extracted from stool and saliva samples.

  25. Oral microbiota changes [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Shotgun metagenomic sequencing of DNA extracted from stool and saliva samples.

  26. Concentration of Imidazole propionate [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Targeted metabolomics

  27. Concentration of Trimethyl amine oxide (TMAO) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Targeted metabolomics

  28. Concentration of p cresol [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Targeted metabolomics

  29. Concentration of indoxyl sulfate [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Targeted metabolomics

  30. Concentration of C reactive protein (CRP) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Fasting serum levels measures

  31. Urinary urea excretion [ Time Frame: Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention ]
    24h urinary sample measure

  32. SF 36 score (short form 36 quality of life questionnaire) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    SF-36 questionnaire

  33. General self efficacy scale score (GSES questionnaire) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    GSES questionnaire

  34. Patient health questionnaire 9 score (PHQ-9 questionnaire) [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    PHQ-9 questionnaire

  35. Gastro-intestinal discomfort changes [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Rome IV criteria

  36. Resting energy expenditure changes [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    Indirect calorimetry (Cosmed Quark RMR)

  37. Epigenetic modifications [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    On serum isolated monocytes for a subgroup of patients

  38. Adipose tissue gene expression modifications [ Time Frame: Change between baseline (T0) and the end of the intervention (T12 weeks) ]
    RNA sequencing of RNA extracted from adipose tissue obtained from adipose tissue aspiration on a subgroup of patients



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03732690


Contacts
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Contact: Karine CLEMENT, MD, PhD 0112177919 karine.clement@aphp.fr
Contact: Pierre BEL LASSEN, MD pierre.bel-lassen@inserm.fr

Locations
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France
Hôpital PITIE SALPETRIERE - APHP Recruiting
Paris, France, 75013
Contact: Karine CLEMENT, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
ICAN Nutrition Education and Research
Investigators
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Principal Investigator: Karine CLEMENT Hôpital PITIE SALPETRIERE - APHP

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03732690     History of Changes
Other Study ID Numbers: P180402J
2018-A01606-49 ( Other Identifier: ANSM )
First Posted: November 7, 2018    Key Record Dates
Last Update Posted: April 29, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Type 2 diabetes
Diet
Protein
Gut microbiota
Metabolites
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases