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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT01731236
First received: January 23, 2012
Last updated: August 26, 2016
Last verified: August 2016
  Purpose
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 Intervention Phase
Dietary Modification
Dietary Supplement: Carnitine
Dietary Supplement: Choline
Drug: Antibiotics
Drug: Choline and Aspirin
Drug: Carnitine and Aspirin
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and cardioVAscuLar Disease

Resource links provided by NLM:


Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Primary Outcome Measure [ Time Frame: December 2017 ] [ Designated as safety issue: No ]
    Plasma levels of carnitine and multiple gut flora metabolites


Secondary Outcome Measures:
  • Secondary Outcome Measures: [ Time Frame: December 2017 ] [ Designated as safety issue: No ]
    alterations in plasma levels of cardio-metabolic risk factors.


Estimated Enrollment: 36
Study Start Date: July 2010
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Ciprofloxacin, Flagyl, Vancomycin, and Neomycin
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 Name: aspirin
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 Name: aspirin

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01731236

Locations
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Principal Investigator: Stanley L Hazen, MD, PhD The Cleveland Clinic
  More Information

Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01731236     History of Changes
Other Study ID Numbers: 10-544 
Study First Received: January 23, 2012
Last Updated: August 26, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by The Cleveland Clinic:
Carnitine metabolism
gut flora

Additional relevant MeSH terms:
Cardiovascular Diseases
Anti-Bacterial Agents
Vancomycin
Ciprofloxacin
Neomycin
Antibiotics, Antitubercular
Aspirin
Metronidazole
Choline
Anti-Infective Agents
Antitubercular Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016