CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and CardioVAscuLar Disease

Early Phase 1

• Conditions: Dietary Modification
• Interventions: Dietary Supplement: Carnitine; Dietary Supplement: Choline; Drug: Antibiotics; Drug: Choline and Aspirin; Drug: Carnitine and Aspirin

• Registration Number: NCT01731236
• Lead Sponsor: The Cleveland Clinic

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.

Study Timeline

• Study Start: 2011-02-11
• Study First Submitted: 2012-01-23
• Study First Submitted QC: 2012-11-16
• Study First Posted: 2012-11-21
• Status Verified: 2024-10
• Last Update Submitted: 2024-11-05
• Last Update Posted: 2024-11-07
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Carnitine (No antibiotics, No aspirin)	Carnitine	L-Carnitine 500 mg capsule by mouth, twice daily for 2 months. No aspirin for 1 month prior to starting study and remains off aspirin during study.
Choline (No Antibiotics, No aspirin)	Choline	Choline 500 mg capsule by mouth, twice daily for 2 months. No aspirin for 1 month prior to starting study and remains off aspirin during study.
Antibiotics	Antibiotics	Antibiotics (Ciprofloxacin, Vancomycin, Metronidazole and Neomycin) Drug: Ciprofloxacin 500 mg, po, twice daily for 7 days (Other Names: Cipro) Drug: Metronidazole 500 mg, po, twice daily for 7 days (Other Names: Flagyl, Noritate, Rosadan, Vandazole, Flagyl ER, Vitazol) Drug: Vancomycin 125 mg, po, 4 times daily for 7 days (Other Names: Vancocin, Vancocin HCl, Pulvules, Vancoled, Novaplus, PremierPro Rx, Vancomycin HCl) Drug: Neomycin 1 gram, po, four times daily for 7 days (Other Names: Aminoglycoside)
Choline and Aspirin	Choline and Aspirin	Choline supplement 500 mg capsule by mouth, twice daily for 2 months Drug: aspirin 81 mg by mouth, daily for 3 months (on aspirin for 1 month prior to starting study and 2 months with Choline supplementation during study) Other Names: Ecotrin, Bufferin, Ascriptin, Fasprin, Norwich Aspirin, Durlaza, Bayer Genuine Aspirin, Genacote, Bayer, Halfprin, Aspirtab, Aspir Low, Aspir-Trin
Carnitine and Aspirin	Carnitine and Aspirin	Carnitine supplement 500 mg capsule by mouth, twice daily for 2 months Drug: aspirin 81 mg by mouth, daily for 3 months (on aspirin for 1 month prior to starting study and 2 months with Carnitine supplementation during study) Other Names: Ecotrin, Bufferin, Ascriptin, Fasprin, Norwich Aspirin, Durlaza, Bayer Genuine Aspirin, Genacote, Bayer, Halfprin, Aspirtab, Aspir Low, Aspir-Trin

Primary Outcome Measures

Name	Time	Method
Primary Outcome Measure	December 2017	Plasma levels of carnitine and multiple gut flora metabolites

Secondary Outcome Measures

Name	Time	Method
Secondary Outcome Measures	December 2017	Alterations in plasma levels of cardio-metabolic risk factors.

Trial Locations

Locations (1)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States