Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)

Cardiovascular Risk Factor Clinical Trial

— GRADY  

Official title:

Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02016430
• Other study ID #: 13-863
• Status: Recruiting
• Phase: N/A
• Start date: April 4, 2014
• Est. completion date: December 2026

Study information

• Verified date: October 2023
• Source: The Cleveland Clinic
• Contact: Jennifer Wilcox
• Phone: 216-636-6153
• Email: kirsopj[@]ccf.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Risk Factor
• Dietary Modification

Intervention

Behavioral:
• MeLT Dietary intervention
Mediterranean diet containing food with low TMAO content.
• TLC Dietary intervention
Standard American Heart Association (AHA) recommendations for dietary counseling.
• MeLT dietary intervention with TMAO
Mediterranean diet containing food with low TMAO content with TMAO levels provided to the subject for guidance.

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in TMAO level	The change in TMAO concentration measured in blood samples	From baseline to 12 weeks follow-up