NCT02016430

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
170

participants targeted

Target at P75+ for not_applicable

Timeline
7mo left

Started Apr 2014

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress96%
Apr 2014Dec 2026

First Submitted

Initial submission to the registry

December 15, 2013

Completed
5 days until next milestone

First Posted

Study publicly available on registry

December 20, 2013

Completed
4 months until next milestone

Study Start

First participant enrolled

April 4, 2014

Completed
12.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2026

Last Updated

October 29, 2025

Status Verified

October 1, 2025

Enrollment Period

12.7 years

First QC Date

December 15, 2013

Last Update Submit

October 28, 2025

Conditions

Dietary ModificationCardiovascular Risk Factor

Keywords

TMAOGut FloraDietary InterventionCholineCarnitine

Outcome Measures

Primary Outcomes (1)

  • Change in TMAO level

    The change in TMAO concentration measured in blood samples

    From baseline to 12 weeks follow-up

Study Arms (3)

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

MeLT Dietary interventionBEHAVIORAL

Mediterranean diet containing food with low TMAO content.

MeLT Dietary intervention
TLC Dietary interventionBEHAVIORAL

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

TLC Dietary intervention
MeLT dietary intervention with TMAOBEHAVIORAL

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

MeLT dietary intervention with TMAO

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Related Publications (5)

  • 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.

    PMID: 21475195BACKGROUND

  • 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.

    PMID: 23563705BACKGROUND

  • 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.

    PMID: 17375117BACKGROUND

  • 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.

    PMID: 17629908BACKGROUND

  • 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.

    PMID: 23614584BACKGROUND

MeSH Terms

Interventions

trimethyloxamine

Study Officials

  • W. H. Wilson Tang, MD

    The Cleveland Clinic

    PRINCIPAL INVESTIGATOR

  • Stanley L. Hazen, MD

    The Cleveland Clinic

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Wilcox

CONTACT

216-636-6153kirsopj@ccf.org

Timothy Engelman, LPN

CONTACT

216-636-6153engelmt@ccf.org

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Staff Cellular and Molecular Medicine and Cardiovascular Medicine

Study Record Dates

First Submitted

December 15, 2013

First Posted

December 20, 2013

Study Start

April 4, 2014

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Last Updated

October 29, 2025

Record last verified: 2025-10

Locations

US(1)