Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)

Study Overview
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Brief Summary
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Our group has recently identified the association between gut-flora-mediated carnitine and phosphatidylcholine metabolism, specifically trimethylamine-N-oxide (TMAO), and cardiovascular risk. This study investigates the ability for dietary intervention to modulate TMAO levels.

Detailed Description
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This is a pilot human study to characterize the relationship between gut flora-associated TMAO generation and dietary intervention. The investigators hypothesize that tailored dietary interventions may help to reduce the ability for gut flora to generate TMAO in individuals with elevated TMAO levels. Specific aims include: To investigate the proportion of subjects with persistently elevated circulating TMAO levels. To compare the amount of TMAO generated from gut flora using stable-isotope-labelled choline, carnitine, and betaine in subjects with elevated versus normal circulating TMAO levels. To evaluate the effect of dietary interventions on the amount of TMAO generated from gut flora using stable-isotope-labelled choline, carnitine, and betaine in subjects with elevated circulating TMAO levels.

Official Title
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Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)

Conditions
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Dietary Modification, Cardiovascular Risk Factor

Intervention / Treatment
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* Behavioral: MeLT Dietary intervention
* Behavioral: TLC Dietary intervention
* Behavioral: MeLT dietary intervention with TMAO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort 1 Inclusion criteria: Men and women age 18 years or above. Elevated TMAO metabolizers (>5 µM) based on screening test and/or eGFR < 60 at most recent measurement. Willing to remain on aspirin or able to be off aspirin or aspirin products for 1 week prior to starting the study and staying on the same aspirin regimen during the duration of the study. Willing to sign the consent form and follow the study protocol, which includes a 12-week dietary modification. Cohort 2 Inclusion criteria: Men and women age 18 years or above. Willing to remain on aspirin or able to be off aspirin or aspirin products for 1 week prior to starting the study and staying on the same aspirin regimen during the duration of the study. Willing to sign the consent form and follow the study protocol. eGFR values ranging from 16-59 Cohort 3 Inclusion criteria: Men and women age 18 years or above. Willing to remain on aspirin or able to be off aspirin or aspirin products for 1 week prior to starting the study and staying on the same aspirin regimen during the duration of the study. Willing to sign the consent form and follow the study protocol. Exclusion Criteria (all cohorts): Significant chronic illness or end-organ dysfunction, including known history of uncompensated heart failure, renal failure, pulmonary disease, hematologic diseases. Active infection or received antibiotics within 2 months of study enrollment Use of over-the-counter probiotic within past month, or ingestion of yogurt within past 7 days Having undergone bariatric procedures or surgeries such as gastric banding or bypass. Pregnancy. Any condition which, in the judgment of the Investigator, would place a patient at undue risk by being enrolled in the trial, or cause inability to comply with the trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MeLT Dietary intervention<br>Mediterranean Low-TMAO (MeLT) diet. Used in cohorts 1, 2 and 3. | Behavioral: MeLT Dietary intervention<br>* Mediterranean diet containing food with low TMAO content.<br>|
| Experimental: TLC Dietary intervention<br>Therapeutic Lifestyle Changes (TLC) diet. Used in cohorts 1, 2 and 3. | Behavioral: TLC Dietary intervention<br>* Standard American Heart Association (AHA) recommendations for dietary counseling.<br>|
| Experimental: MeLT dietary intervention with TMAO<br>Mediterranean Low TMAO diet with TMAO levels reported. Used in cohort 1 only. | Behavioral: MeLT dietary intervention with TMAO<br>* Mediterranean diet containing food with low TMAO content with TMAO levels provided to the subject for guidance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TMAO level | The change in TMAO concentration measured in blood samples | From baseline to 12 weeks follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMAO, Gut Flora, Dietary Intervention, Choline, Carnitine