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

October 27, 2023 updated by: Wilson Tang, The Cleveland Clinic
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Timothy Engelman, LPN
  • Phone Number: 216-636-6153
  • Email: engelmt@ccf.org

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Principal Investigator:
          • Stanley L. Hazen, MD
        • Contact:
        • Principal Investigator:
          • W. H. Wilson Tang, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Cleveland Clinic

Investigators

  • Principal Investigator: Stanley L. Hazen, MD, The Cleveland Clinic
  • Principal Investigator: W. H. Wilson Tang, MD, The Cleveland Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 4, 2014

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

December 15, 2013

First Submitted That Met QC Criteria

December 19, 2013

First Posted (Estimated)

December 20, 2013

Study Record Updates

Last Update Posted (Actual)

October 30, 2023

Last Update Submitted That Met QC Criteria

October 27, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 13-863

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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