CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and cardioVAscuLar Disease
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Carnitine (No antibiotics, No aspirin) 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
Group 1: Carnitine supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study)
|
| Active Comparator: Choline (No Antibiotics, No aspirin) 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
Group 2: Choline supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study)
|
| Active Comparator: 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) |
Drug: Antibiotics
Group 3: Carnitine or Choline for 2 months, antibiotic cocktail (Ciprofloxacin, Flagyl, Vancomycin, and Neomycin) for 1 week
Other Names:
|
| Active Comparator: 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 |
Drug: Choline and Aspirin
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).
Other Names:
|
| Active Comparator: 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 |
Drug: Carnitine and Aspirin
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).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Primary Outcome Measure [December 2017]
Plasma levels of carnitine and multiple gut flora metabolites
Secondary Outcome Measures
- Secondary Outcome Measures [December 2017]
Alterations in plasma levels of cardio-metabolic risk factors.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
Sponsors and Collaborators
- The Cleveland Clinic
Investigators
- Principal Investigator: Stanley L Hazen, MD, PhD, The Cleveland Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 10-544