Dietary ModificationGRADYNCT02016430
Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)
A study testing MeLT Dietary intervention, TLC Dietary intervention and MeLT dietary intervention with TMAO in people with Dietary Modification and Cardiovascular Risk Factor, run by The Cleveland Clinic at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Dietary Modification, Cardiovascular Risk Factor
- What is being tested?
- MeLT Dietary intervention, TLC Dietary intervention and MeLT dietary intervention with TMAO
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2014to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
Show all 14Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Jennifer D Wilcox, BA, 216-636-6153, kirsopj@ccf.org
W. H. Wilson Tang, MD
About this study
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.
Read the 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.
- Conditions
- Dietary Modification, Cardiovascular Risk Factor
- Being tested
- MeLT Dietary intervention, TLC Dietary intervention, MeLT dietary intervention with TMAO
- Keywords
- TMAO, Gut Flora, Dietary Intervention, Choline, Carnitine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MeLT Dietary interventionBehavioural
Mediterranean diet containing food with low TMAO content.
TLC Dietary interventionBehavioural
Standard American Heart Association (AHA) recommendations for dietary counseling.
MeLT dietary intervention with TMAOBehavioural
Mediterranean diet containing food with low TMAO content with TMAO levels provided to the subject for guidance.
| Study group | Role | What they receive |
|---|---|---|
| MeLT Dietary intervention | Experimental | Mediterranean Low-TMAO (MeLT) diet. Used in cohorts 1, 2 and 3. Receives: Behavioral: MeLT Dietary intervention |
| TLC Dietary intervention | Experimental | Therapeutic Lifestyle Changes (TLC) diet. Used in cohorts 1, 2 and 3. Receives: Behavioral: TLC Dietary intervention |
| MeLT dietary intervention with TMAO | Experimental | Mediterranean Low TMAO diet with TMAO levels reported. Used in cohort 1 only. Receives: Behavioral: MeLT dietary intervention with TMAO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in TMAO level
The change in TMAO concentration measured in blood samples
Measured: From baseline to 12 weeks follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2013 (estimated)
- Study start4 Apr 2014
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Dietary ModificationStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wilson Tang, The Cleveland Clinic
- Investigators
- W. H. Wilson Tang, MD, Principal investigator, The Cleveland ClinicStanley L. Hazen, MD, PhD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02016430
- Sponsor's protocol ID
- 13-863
- Acronym
- GRADY
- Status last verified
- Jun 2026
- First submitted
- 15 Dec 2013
- Last updated
- 25 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 21475195Koeth 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.
PubMed 23563705Dalmeijer 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.
PubMed 17375117Bidulescu 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.
PubMed 17629908Tang 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.
PubMed 23614584
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)
- ClinicalTrials.gov ID
- NCT02016430
- Acronym / sponsor ID
- GRADY / 13-863
- Conditions
- Dietary Modification, Cardiovascular Risk Factor
- Keywords
- TMAO, Gut Flora, Dietary Intervention, Choline, Carnitine
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 170 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 4 Apr 2014 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 20 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MeLT Dietary intervention | Experimental | Behavioral: MeLT Dietary interventionMediterranean Low-TMAO (MeLT) diet. Used in cohorts 1, 2 and 3. |
| TLC Dietary intervention | Experimental | Behavioral: TLC Dietary interventionTherapeutic Lifestyle Changes (TLC) diet. Used in cohorts 1, 2 and 3. |
| MeLT dietary intervention with TMAO | Experimental | Behavioral: MeLT dietary intervention with TMAOMediterranean Low TMAO diet with TMAO levels reported. Used in cohort 1 only. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MeLT Dietary interventionMediterranean diet containing food with low TMAO content. | Behavioural | MeLT Dietary intervention |
| TLC Dietary interventionStandard American Heart Association (AHA) recommendations for dietary counseling. | Behavioural | TLC Dietary intervention |
| MeLT dietary intervention with TMAOMediterranean diet containing food with low TMAO content with TMAO levels provided to the subject for guidance. | Behavioural | MeLT dietary intervention with TMAO |
Primary outcome
Change in TMAO level
Time frame: From baseline to 12 weeks follow-up
The change in TMAO concentration measured in blood samples
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Background: PubMed 21475195Wang 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.
- Background: PubMed 23563705Koeth 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.
- Background: PubMed 17375117Dalmeijer 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.
- Background: PubMed 17629908Bidulescu 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.
- Background: PubMed 23614584Tang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
W. H. Wilson Tang, MD principal investigator
The Cleveland Clinic
Stanley L. Hazen, MD, PhD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MeLT Dietary intervention, TLC Dietary intervention and MeLT dietary intervention with TMAO in people with Dietary Modification and Cardiovascular Risk Factor, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jennifer Wilcox, BA (216-636-6153, kirsopj@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in TMAO level (time frame: From baseline to 12 weeks follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02016430, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.