Gut Flora Metabolite Reduction After Dietary Intervention (GRADY)

NeuroTherapia, Inc.

Status: Enrolling

Conditions: Dietary Modification; Cardiovascular Risk Factor

Treatments: Behavioral: TLC Dietary intervention; Behavioral: MeLT dietary intervention with TMAO; Behavioral: MeLT Dietary intervention

Study type: Interventional

Funder types: Other

Identifiers

NCT02016430

13-863

Details and patient eligibility

About

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.

Full 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.

Enrollment: 170 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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170 participants in 3 patient groups

MeLT Dietary intervention

Experimental group

Description:

Mediterranean Low-TMAO (MeLT) diet. Used in cohorts 1, 2 and 3.

Treatment:

Behavioral: MeLT Dietary intervention

TLC Dietary intervention

Experimental group

Description:

Therapeutic Lifestyle Changes (TLC) diet. Used in cohorts 1, 2 and 3.

Treatment:

Behavioral: TLC Dietary intervention

MeLT dietary intervention with TMAO

Experimental group

Description:

Mediterranean Low TMAO diet with TMAO levels reported. Used in cohort 1 only.

Treatment:

Behavioral: MeLT dietary intervention with TMAO