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

Study Overview
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Brief Summary
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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
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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.

Official Title
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CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and cardioVAscuLar Disease

Conditions
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Dietary Modification

Intervention / Treatment
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* Dietary Supplement: Carnitine
* Dietary Supplement: Choline
* Drug: Antibiotics
* Drug: Choline and Aspirin
* Drug: Carnitine and Aspirin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Carnitine (No antibiotics, No aspirin)<br>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. | Dietary Supplement: Carnitine<br>* Group 1: Carnitine supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study)<br>|
| Active Comparator: Choline (No Antibiotics, No aspirin)<br>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. | Dietary Supplement: Choline<br>* Group 2: Choline supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study)<br>|
| Active Comparator: Antibiotics<br>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) | Drug: Antibiotics<br>* Group 3: Carnitine or Choline for 2 months, antibiotic cocktail (Ciprofloxacin, Flagyl, Vancomycin, and Neomycin) for 1 week<br>* Other names: Ciprofloxacin, Flagyl, Vancomycin, and Neomycin;|
| Active Comparator: Choline and Aspirin<br>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 | Drug: Choline and Aspirin<br>* Group 4: Choline supplement for 2 months plus aspirin 81 mg for 3 months (1 month prior to starting the study and 2 months during the study).<br>* Other names: aspirin;|
| Active Comparator: Carnitine and Aspirin<br>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 | Drug: Carnitine and Aspirin<br>* Group 5: Carnitine supplement for 2 months plus aspirin 81 mg for 3 months (1 month prior to starting the study and 2 months during the study).<br>* Other names: aspirin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome Measure | Plasma levels of carnitine and multiple gut flora metabolites | December 2017 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome Measures | Alterations in plasma levels of cardio-metabolic risk factors. | December 2017 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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carnitine metabolism, gut flora, phosphatidylcholine