Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)

Not Applicable

Recruiting

• Conditions: Dietary Modification; Cardiovascular Risk Factor
• Interventions: Behavioral: MeLT Dietary intervention; Behavioral: MeLT dietary intervention with TMAO; Behavioral: TLC Dietary intervention

• Registration Number: NCT02016430
• Lead Sponsor: The Cleveland Clinic

Brief Summary

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

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:

1. To investigate the proportion of subjects with persistently elevated circulating TMAO levels.

2. 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.

3. 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.

Study Timeline

• Study First Submitted: 2013-12-15
• Study First Submitted QC: 2013-12-19
• Study First Posted: 2013-12-20
• Study Start: 2014-04-04
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-11-27
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 170

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MeLT Dietary intervention	MeLT Dietary intervention	Mediterranean Low-TMAO (MeLT) diet. Used in cohorts 1, 2 and 3.
MeLT dietary intervention with TMAO	MeLT dietary intervention with TMAO	Mediterranean Low TMAO diet with TMAO levels reported. Used in cohort 1 only.
TLC Dietary intervention	TLC Dietary intervention	Therapeutic Lifestyle Changes (TLC) diet. Used in cohorts 1, 2 and 3.

Primary Outcome Measures

Name	Time	Method
Change in TMAO level	From baseline to 12 weeks follow-up	The change in TMAO concentration measured in blood samples

Trial Locations

Locations (1)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States