Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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:
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To investigate the proportion of subjects with persistently elevated circulating TMAO levels.
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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.
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MeLT Dietary intervention Mediterranean Low-TMAO (MeLT) diet |
Behavioral: MeLT Dietary intervention
Mediterranean diet containing food with low TMAO content.
|
| Experimental: TLC Dietary intervention Therapeutic Lifestyle Changes (TLC) diet |
Behavioral: TLC Dietary intervention
Standard American Heart Association (AHA) recommendations for dietary counseling
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| Experimental: MeLT dietary intervention with TMAO Mediterranean Low TMAO diet with TMAO levels reported |
Behavioral: MeLT dietary intervention with TMAO
Mediterranean diet containing food with low TMAO content with TMAO levels provided to the subject for guidance.
|
Outcome Measures
Primary Outcome Measures
- Change in TMAO level [From baseline to 12 weeks follow-up]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Men and women age 18 years or above.
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Elevated TMAO metabolizers (>5 µM) based on screening test.
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Willing to remain on aspirin or able to be off aspirin or aspirin products for 1 week prior to starting study and staying on the same aspirin regimen during the duration of the 12-week study.
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Willing to sign consent form or to follow study protocol, which includes 12-week dietary modification.
Exclusion Criteria:
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Significant chronic illness or end-organ dysfunction, including known history of uncompensated heart failure, renal failure, pulmonary disease, hematologic diseases.
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Active infection or received antibiotics within 2 months of study enrollment
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Use of over-the-counter probiotic within past month, or ingestion of yogurt within past 7 days
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Having undergone bariatric procedures or surgeries such as gastric banding or bypass.
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Pregnancy.
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
Sponsors and Collaborators
- The Cleveland Clinic
Investigators
- Principal Investigator: W. H. Wilson Tang, MD, The Cleveland Clinic
- Principal Investigator: Stanley L. Hazen, MD, The Cleveland Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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. Epub 2007 Mar 21.
- 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.
- 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.
- 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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