Gut Flora Metabolite Reduction After Dietary Intervention... | NCT02016430

Studies
Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)

NCT02016430

Sponsor

The Cleveland Clinic

Status

Recruiting

Last Update Posted

Jun 25, 2026Actual

Enrollment

170Estimated

Phase

Not Applicable

Conditions

Dietary Modification
Cardiovascular Risk Factor

Interventions

MeLT Dietary intervention
TLC Dietary intervention
MeLT dietary intervention with TMAO

Countries

United States

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Jun 2026

Overall Recruitment Status or Expanded Access Status

Recruiting

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Apr 4, 2014Actual

Primary Completion Date

Dec 2026Estimated

Completion Date

Dec 2026Estimated

First Submitted Date

Dec 15, 2013

First Submission Date that Met QC Criteria

Dec 19, 2013

First Posted Date

Dec 20, 2013Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Jun 23, 2026

Last Update Posted Date

Jun 25, 2026Actual

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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:

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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Not Applicable

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

170Estimated

Arms/Interventions Module

Arm Groups

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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
MeLT Dietary intervention	Behavioral	Mediterranean diet containing food with low TMAO content.	MeLT Dietary intervention

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

Eligibility Module

Eligibility Criteria

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

Accepts Healthy Volunteers

Yes

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Name	Role	Phone	Extension	Email
Jennifer Wilcox, BA	Contact	216-636-6153		kirsopj@ccf.org
Valesha Province, MA	Contact	216-636-6153		provinv@ccf.org

Name	Affiliation	Role
W. H. Wilson Tang, MD	The Cleveland Clinic	Principal Investigator
Stanley L. Hazen, MD, PhD	The Cleveland Clinic	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Cleveland Clinic	Recruiting	Cleveland	Ohio	44195	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
21475195	Background	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.
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