Ignite Creation Date:
2024-05-06 @ 12:20 PM
Last Modification Date:
2024-10-26 @ 12:57 PM
Study NCT ID:
NCT03732690
Status:
COMPLETED
Last Update Posted:
2021-09-10
First Post:
2018-10-22
Brief Title:
The Interaction Between Protein Intake Gut Microbiota and Type 2 Diabetes in Subjects With Different Ethnic Backgrounds
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2021-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MICRODIET
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 N80 and Caribbean N40 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
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 N80 and Caribbean N40 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
Detailed Description:
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 Moreover it has been shown that the response to a dietary intervention may depend on the baseline gut microbiome richness
Main hypothesis 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
Study population
Individuals with type 2 diabetes T2D of Caucasian or Caribbean origin 120 patients will be included in total
Intervention
Assignment after randomization to one of the following 2 diets
HP diet high protein High Protein HP diet with 30 protein 40 carbohydrate and 30 fat as of total energy intake
LP diet low protein diet Low Protein LP with 10 protein 55 carbohydrate and 35 fat as of total energy intake Food boxes adapted to each diet HP or LP pre-cooked meals HP or LP 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
Subjects are required to keep food diaries three days a week and will also have weekly contact with a dietician
Visits
- Inclusion visit V0 maximum 1 month before V1 Participants will first be recruited from the diabetic population of the French cohort of the European project METACARDIS Individuals eligible for the study are screened for inclusion
Baseline phenotyping is performed metabolic inflammatory blood markers stool and oral microbiota sampling body composition by DXA questionnaires
- Randomization visit V1 T0 - start of the intervention Randomization into 2 parallel groups High Protein or Low protein diet will be stratified based on metagenomics richness obtained from Metacardis results age or 60 gender ethnic background Caribbean or Caucasian
Meal tolerance test anthropometric measures resting energy expenditure measure one week CGMS 24h urinary urea measure are performed
- Follow-up visit V2 T42 - 7 days Mid protocol visit with anthropometric measures one week CGMS 24h urinary urea measures stool sampling
- End of study visit V3 T84 - 7 days Phenotyping is performed metabolic inflammatory blood markers stool and oral microbiota sampling body composition by DXA questionnaires meal tolerance test anthropometric measures resting energy expenditure measure one week CGMS 24h urinary urea measure
Statistical analysis
There are no multiple hypotheses since our study has only one primary objective AUC delta of the glycemic excursion after a mixed meal tolerance test MMT between the beginning of study and 3 months post intervention Thus the problem of the type 1 error will not arise
The primary endpoint will be analyzed to compare changes in AUC for glycemic excursion versus diet rich vs low protein based on initial metagenomic richness high vs low and ethnicity Caucasian vs Caribbean AUC changes after dietary intervention between the different groups will be tested using linear regression models for repeated measurements with adjustment for initial levels The effect of diet composition within the groups will be tested using Bonferronis post-hoc covariance analysis ANCOVA analyzes For secondary endpoints the same approaches will be used for analysis of postprandial metabolites AUC AUC post-MMT variation Differences in relative abundance of bacterial species and functional modules generated by metagenomic sequencing and quality of life questionnaires will also be analyzed by subgroups using uni multivariate analyzes Correlations will be sought between changes in bio-clinical variables and changes in measurements of different metabolites
Funding
European Program Join Program Initiative JPI HDHL ERA-NET cofund HDHL-INTIMIC -Edition 2017 through the National Agency for Research ANR
Leducq Foundation Research Grant 17CVD01 titled Gut Microbiome as a Target for the Treatment of Cardiometabolic Diseases
K Santé Society providing meals for the study
Nutrisens Society providing snacks for the study
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 Moreover it has been shown that the response to a dietary intervention may depend on the baseline gut microbiome richness
Main hypothesis 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
Study population
Individuals with type 2 diabetes T2D of Caucasian or Caribbean origin 120 patients will be included in total
Intervention
Assignment after randomization to one of the following 2 diets
HP diet high protein High Protein HP diet with 30 protein 40 carbohydrate and 30 fat as of total energy intake
LP diet low protein diet Low Protein LP with 10 protein 55 carbohydrate and 35 fat as of total energy intake Food boxes adapted to each diet HP or LP pre-cooked meals HP or LP 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
Subjects are required to keep food diaries three days a week and will also have weekly contact with a dietician
Visits
- Inclusion visit V0 maximum 1 month before V1 Participants will first be recruited from the diabetic population of the French cohort of the European project METACARDIS Individuals eligible for the study are screened for inclusion
Baseline phenotyping is performed metabolic inflammatory blood markers stool and oral microbiota sampling body composition by DXA questionnaires
- Randomization visit V1 T0 - start of the intervention Randomization into 2 parallel groups High Protein or Low protein diet will be stratified based on metagenomics richness obtained from Metacardis results age or 60 gender ethnic background Caribbean or Caucasian
Meal tolerance test anthropometric measures resting energy expenditure measure one week CGMS 24h urinary urea measure are performed
- Follow-up visit V2 T42 - 7 days Mid protocol visit with anthropometric measures one week CGMS 24h urinary urea measures stool sampling
- End of study visit V3 T84 - 7 days Phenotyping is performed metabolic inflammatory blood markers stool and oral microbiota sampling body composition by DXA questionnaires meal tolerance test anthropometric measures resting energy expenditure measure one week CGMS 24h urinary urea measure
Statistical analysis
There are no multiple hypotheses since our study has only one primary objective AUC delta of the glycemic excursion after a mixed meal tolerance test MMT between the beginning of study and 3 months post intervention Thus the problem of the type 1 error will not arise
The primary endpoint will be analyzed to compare changes in AUC for glycemic excursion versus diet rich vs low protein based on initial metagenomic richness high vs low and ethnicity Caucasian vs Caribbean AUC changes after dietary intervention between the different groups will be tested using linear regression models for repeated measurements with adjustment for initial levels The effect of diet composition within the groups will be tested using Bonferronis post-hoc covariance analysis ANCOVA analyzes For secondary endpoints the same approaches will be used for analysis of postprandial metabolites AUC AUC post-MMT variation Differences in relative abundance of bacterial species and functional modules generated by metagenomic sequencing and quality of life questionnaires will also be analyzed by subgroups using uni multivariate analyzes Correlations will be sought between changes in bio-clinical variables and changes in measurements of different metabolites
Funding
European Program Join Program Initiative JPI HDHL ERA-NET cofund HDHL-INTIMIC -Edition 2017 through the National Agency for Research ANR
Leducq Foundation Research Grant 17CVD01 titled Gut Microbiome as a Target for the Treatment of Cardiometabolic Diseases
K Santé Society providing meals for the study
Nutrisens Society providing snacks for the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2018-A01606-49 | OTHER | ANSM | None |