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

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

Tracking Information

• First Submitted Date: January 23, 2012
• First Posted Date: November 21, 2012
• Last Update Posted Date: September 30, 2022
• Actual Study Start Date: February 11, 2011
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 1, 2016)

Primary Outcome Measure [ Time Frame: December 2017 ]

Plasma levels of carnitine and multiple gut flora metabolites

Original Primary Outcome Measures (submitted: November 16, 2012)

Primary Outcome Measure

Plasma levels of carnitine and multiple gut flora metabolites

Current Secondary Outcome Measures (submitted: July 23, 2019)

Secondary Outcome Measures [ Time Frame: December 2017 ]

Alterations in plasma levels of cardio-metabolic risk factors.

Original Secondary Outcome Measures (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: CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and cardioVAscuLar Disease
• Official Title: 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: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Dietary Modification

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: July 13, 2017): 100
• Original Estimated Enrollment (submitted: November 16, 2012): 36
• Estimated Study Completion Date: June 2025
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01731236
• Other Study ID Numbers: 10-544
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• 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: The Cleveland Clinic
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Stanley L Hazen, MD, PhD; The Cleveland Clinic

• PRS Account: The Cleveland Clinic
• Verification Date: September 2022