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

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ClinicalTrials.gov Identifier: NCT01731236
Recruitment Status : Enrolling by invitation
First Posted : November 21, 2012
Last Update Posted : September 30, 2022
Sponsor:
Information provided by (Responsible Party):
Stanley L Hazen, MD, PhD, The Cleveland Clinic

Tracking Information
First Submitted Date  ICMJE January 23, 2012
First Posted Date  ICMJE November 21, 2012
Last Update Posted Date September 30, 2022
Actual Study Start Date  ICMJE February 11, 2011
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 1, 2016)
Primary Outcome Measure [ Time Frame: December 2017 ]
Plasma levels of carnitine and multiple gut flora metabolites
Original Primary Outcome Measures  ICMJE
 (submitted: November 16, 2012)
Primary Outcome Measure
Plasma levels of carnitine and multiple gut flora metabolites
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2019)
Secondary Outcome Measures [ Time Frame: December 2017 ]
Alterations in plasma levels of cardio-metabolic risk factors.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2012)
Secondary Outcome Measures:
alterations in plasma levels of cardio-metabolic risk factors.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and cardioVAscuLar Disease
Official Title  ICMJE CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and cardioVAscuLar Disease
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 Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Dietary Modification
Intervention  ICMJE
  • Dietary Supplement: Carnitine
    Group 1: Carnitine supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and 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)
  • 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
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Dietary Supplement: Carnitine
  • 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.
    Intervention: Dietary Supplement: Choline
  • 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)

    Intervention: Drug: Antibiotics
  • 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

    Intervention: Drug: Choline and 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

    Intervention: Drug: Carnitine and Aspirin
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: July 13, 2017)
100
Original Estimated Enrollment  ICMJE
 (submitted: November 16, 2012)
36
Estimated Study Completion Date  ICMJE June 2025
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01731236
Other Study ID Numbers  ICMJE 10-544
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Stanley L Hazen, MD, PhD, The Cleveland Clinic
Original Responsible Party The Cleveland Clinic
Current Study Sponsor  ICMJE The Cleveland Clinic
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Stanley L Hazen, MD, PhD The Cleveland Clinic
PRS Account The Cleveland Clinic
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP