Clinical trial NCT01731236: CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and CardioVAscuLar Disease
Official title: CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and CardioVAscuLar Disease
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: EARLY_PHASE1
Conditions: Dietary Modification
Keywords: carnitine metabolism
gut flora
phosphatidylcholine
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2012-11-21
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The principal goal for the study is to examine the role gut flora plays in modulating metabolism of dietary carnitine and choline in humans.

Detailed description: The principal goal for the study is to examine the role gut flora plays in modulating metabolism of dietary trimethylamine nutrients in humans. We have recently shown that dietary intake of two trimethylamines abundant in animal products, carnitine and the choline group of phosphatidylcholine (PC), are mechanistically linked to cardiovascular disease risk. We wish to further explore the metabolism of these nutrients in humans, and to test the hypothesis that the intestinal micro flora (gut flora) plays a critical role in generation of metabolites from dietary carnitine and choline/PC linked to cardiometabolic disease. We further hypothesize that the production of specific metabolites of carnitine and choline/PC are influenced by the composition of gut flora, and these may be altered by the preceding dietary patterns of the subjects. We therefore wish to test whether dietary supplementation with carnitine and/or choline alters the metabolism of carnitine and choline/PC in subjects. We also hypothesize that transient suppression or modulation of gut flora via short-term broad spectrum antibiotic therapy, or by reconstitution of micro flora composition via probiotic therapy, in healthy subjects, can alter the metabolism of carnitine and choline/PC. We will also examine the impact of low dose aspirin on these pathways by examining subjects before versus after taking aspirin.

Eligibility criteria: Inclusion Criteria:

* Men and women age 18 years or above.
* Able to provide informed consent and comply with study protocol

Exclusion Criteria:

* Significant chronic illness or end-organ dysfunction, including known history of heart failure, renal failure, pulmonary disease, hematologic diseases or pregnancy.
* Active infection or received antibiotics within 2 months of study enrollment
* Use of Over-The-Counter (OTC) probiotic within past 2 months, or ingestion of yogurt within past 7 days
* Chronic gastrointestinal disorders, or intolerance to probiotic therapy
* Having undergone Bariatric procedures or surgeries such as gastric banding or bypass

Primary outcomes:
measure: Primary Outcome Measure
timeFrame: December 2017
Secondary outcomes:
measure: Secondary Outcome Measures
timeFrame: December 2017
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Stanley L Hazen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koeth RA, Lam-Galvez BR, Kirsop J, Wang Z, Levison BS, Gu X, Copeland MF, Bartlett D, Cody DB, Dai HJ, Culley MK, Li XS, Fu X, Wu Y, Li L, DiDonato JA, Tang WHW, Garcia-Garcia JC, Hazen SL. l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. J Clin Invest. 2019 Jan 2;129(1):373-387. doi: 10.1172/JCI94601. Epub 2018 Dec 10.