Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)

NCT ID: NCT02016430

Last Updated: 2025-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

170 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-04

Study Completion Date

2026-12-31

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:

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.

Conditions

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Dietary Modification Cardiovascular Risk Factor

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MeLT Dietary intervention

Mediterranean Low-TMAO (MeLT) diet. Used in cohorts 1, 2 and 3.

Group Type EXPERIMENTAL

MeLT Dietary intervention

Intervention Type BEHAVIORAL

Mediterranean diet containing food with low TMAO content.

TLC Dietary intervention

Therapeutic Lifestyle Changes (TLC) diet. Used in cohorts 1, 2 and 3.

Group Type EXPERIMENTAL

TLC Dietary intervention

Intervention Type BEHAVIORAL

Standard American Heart Association (AHA) recommendations for dietary counseling.

MeLT dietary intervention with TMAO

Mediterranean Low TMAO diet with TMAO levels reported. Used in cohort 1 only.

Group Type EXPERIMENTAL

MeLT dietary intervention with TMAO

Intervention Type BEHAVIORAL

Mediterranean diet containing food with low TMAO content with TMAO levels provided to the subject for guidance.

Interventions

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MeLT Dietary intervention

Mediterranean diet containing food with low TMAO content.

Intervention Type BEHAVIORAL

TLC Dietary intervention

Standard American Heart Association (AHA) recommendations for dietary counseling.

Intervention Type BEHAVIORAL

MeLT dietary intervention with TMAO

Mediterranean diet containing food with low TMAO content with TMAO levels provided to the subject for guidance.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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.


* 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


* 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

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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The Cleveland Clinic

OTHER

Sponsor Role lead

Responsible Party

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Wilson Tang

Staff Cellular and Molecular Medicine and Cardiovascular Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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W. H. Wilson Tang, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Stanley L. Hazen, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jennifer Wilcox

Role: CONTACT

216-636-6153

Timothy Engelman, LPN

Role: CONTACT

216-636-6153

Facility Contacts

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Jennifer Wilcox

Role: primary

216-636-6153

References

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Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922.

Reference Type BACKGROUND
PMID: 21475195 (View on PubMed)

Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145. Epub 2013 Apr 7.

Reference Type BACKGROUND
PMID: 23563705 (View on PubMed)

Dalmeijer GW, Olthof MR, Verhoef P, Bots ML, van der Schouw YT. Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women. Eur J Clin Nutr. 2008 Mar;62(3):386-94. doi: 10.1038/sj.ejcn.1602725. Epub 2007 Mar 21.

Reference Type BACKGROUND
PMID: 17375117 (View on PubMed)

Bidulescu A, Chambless LE, Siega-Riz AM, Zeisel SH, Heiss G. Usual choline and betaine dietary intake and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. BMC Cardiovasc Disord. 2007 Jul 13;7:20. doi: 10.1186/1471-2261-7-20.

Reference Type BACKGROUND
PMID: 17629908 (View on PubMed)

Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400.

Reference Type BACKGROUND
PMID: 23614584 (View on PubMed)

Other Identifiers

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13-863

Identifier Type: -

Identifier Source: org_study_id

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