<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01731236</url>
  </required_header>
  <id_info>
    <org_study_id>10-544</org_study_id>
    <nct_id>NCT01731236</nct_id>
  </id_info>
  <brief_title>CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and cardioVAscuLar Disease</brief_title>
  <acronym>CARNIVAL</acronym>
  <official_title>CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and cardioVAscuLar Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The principal goal for the study is to examine the role gut flora plays in modulating&#xD;
      metabolism of dietary carnitine and choline in humans.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The principal goal for the study is to examine the role gut flora plays in modulating&#xD;
      metabolism of dietary trimethylamine nutrients in humans. We have recently shown that dietary&#xD;
      intake of two trimethylamines abundant in animal products, carnitine and the choline group of&#xD;
      phosphatidylcholine (PC), are mechanistically linked to cardiovascular disease risk. We wish&#xD;
      to further explore the metabolism of these nutrients in humans, and to test the hypothesis&#xD;
      that the intestinal micro flora (gut flora) plays a critical role in generation of&#xD;
      metabolites from dietary carnitine and choline/PC linked to cardiometabolic disease. We&#xD;
      further hypothesize that the production of specific metabolites of carnitine and choline/PC&#xD;
      are influenced by the composition of gut flora, and these may be altered by the preceding&#xD;
      dietary patterns of the subjects. We therefore wish to test whether dietary supplementation&#xD;
      with carnitine and/or choline alters the metabolism of carnitine and choline/PC in subjects.&#xD;
      We also hypothesize that transient suppression or modulation of gut flora via short-term&#xD;
      broad spectrum antibiotic therapy, or by reconstitution of micro flora composition via&#xD;
      probiotic therapy, in healthy subjects, can alter the metabolism of carnitine and choline/PC.&#xD;
      We will also examine the impact of low dose aspirin on these pathways by examining subjects&#xD;
      before versus after taking aspirin.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">February 11, 2011</start_date>
  <completion_date type="Anticipated">June 2025</completion_date>
  <primary_completion_date type="Anticipated">June 2025</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary Outcome Measure</measure>
    <time_frame>December 2017</time_frame>
    <description>Plasma levels of carnitine and multiple gut flora metabolites</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary Outcome Measures</measure>
    <time_frame>December 2017</time_frame>
    <description>Alterations in plasma levels of cardio-metabolic risk factors.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Dietary Modification</condition>
  <arm_group>
    <arm_group_label>Carnitine (No antibiotics, No aspirin)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Choline (No Antibiotics, No aspirin)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Antibiotics</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Antibiotics (Ciprofloxacin, Vancomycin, Metronidazole and Neomycin) Drug: Ciprofloxacin 500 mg, po, twice daily for 7 days (Other Names: Cipro)&#xD;
Drug: Metronidazole 500 mg, po, twice daily for 7 days (Other Names: Flagyl, Noritate, Rosadan, Vandazole, Flagyl ER, Vitazol)&#xD;
Drug: Vancomycin 125 mg, po, 4 times daily for 7 days (Other Names: Vancocin, Vancocin HCl, Pulvules, Vancoled, Novaplus, PremierPro Rx, Vancomycin HCl)&#xD;
Drug: Neomycin 1 gram, po, four times daily for 7 days (Other Names: Aminoglycoside)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Choline and Aspirin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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)&#xD;
Other Names:&#xD;
Ecotrin, Bufferin, Ascriptin, Fasprin, Norwich Aspirin, Durlaza, Bayer Genuine Aspirin, Genacote, Bayer, Halfprin, Aspirtab, Aspir Low, Aspir-Trin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carnitine and Aspirin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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)&#xD;
Other Names:&#xD;
Ecotrin, Bufferin, Ascriptin, Fasprin, Norwich Aspirin, Durlaza, Bayer Genuine Aspirin, Genacote, Bayer, Halfprin, Aspirtab, Aspir Low, Aspir-Trin</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Carnitine</intervention_name>
    <description>Group 1: Carnitine supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study)</description>
    <arm_group_label>Carnitine (No antibiotics, No aspirin)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Choline</intervention_name>
    <description>Group 2: Choline supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study)</description>
    <arm_group_label>Choline (No Antibiotics, No aspirin)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antibiotics</intervention_name>
    <description>Group 3: Carnitine or Choline for 2 months, antibiotic cocktail (Ciprofloxacin, Flagyl, Vancomycin, and Neomycin) for 1 week</description>
    <arm_group_label>Antibiotics</arm_group_label>
    <other_name>Ciprofloxacin, Flagyl, Vancomycin, and Neomycin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Choline and Aspirin</intervention_name>
    <description>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).</description>
    <arm_group_label>Choline and Aspirin</arm_group_label>
    <other_name>aspirin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carnitine and Aspirin</intervention_name>
    <description>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).</description>
    <arm_group_label>Carnitine and Aspirin</arm_group_label>
    <other_name>aspirin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women age 18 years or above.&#xD;
&#xD;
          -  Able to provide informed consent and comply with study protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant chronic illness or end-organ dysfunction, including known history of heart&#xD;
             failure, renal failure, pulmonary disease, hematologic diseases or pregnancy.&#xD;
&#xD;
          -  Active infection or received antibiotics within 2 months of study enrollment&#xD;
&#xD;
          -  Use of Over-The-Counter (OTC) probiotic within past 2 months, or ingestion of yogurt&#xD;
             within past 7 days&#xD;
&#xD;
          -  Chronic gastrointestinal disorders, or intolerance to probiotic therapy&#xD;
&#xD;
          -  Having undergone Bariatric procedures or surgeries such as gastric banding or bypass&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stanley L Hazen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 23, 2012</study_first_submitted>
  <study_first_submitted_qc>November 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>September 28, 2022</last_update_submitted>
  <last_update_submitted_qc>September 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Stanley L Hazen, MD, PhD</investigator_full_name>
    <investigator_title>Primary Investigator</investigator_title>
  </responsible_party>
  <keyword>carnitine metabolism</keyword>
  <keyword>gut flora</keyword>
  <keyword>phosphatidylcholine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Vancomycin</mesh_term>
    <mesh_term>Ciprofloxacin</mesh_term>
    <mesh_term>Neomycin</mesh_term>
    <mesh_term>Choline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01731236
org study id: 10-544
nct id: NCT01731236
lead sponsor: 
has dmc: No
The principal goal for the study is to examine the role gut flora plays in modulating
      metabolism of dietary carnitine and choline in humans.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Primary Outcome Measure
time frame: December 2017
description: Plasma levels of carnitine and multiple gut flora metabolites
measure: Secondary Outcome Measures
time frame: December 2017
description: Alterations in plasma levels of cardio-metabolic risk factors.
arm group label: Carnitine (No antibiotics, No aspirin)
arm group type: Active Comparator
description: 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.
arm group label: Choline (No Antibiotics, No aspirin)
arm group type: Active Comparator
description: 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.
arm group label: Antibiotics
arm group type: Active Comparator
description: 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)
arm group label: Choline and Aspirin
arm group type: Active Comparator
description: 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
arm group label: Carnitine and Aspirin
arm group type: Active Comparator
description: 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 type: Dietary Supplement
intervention name: Carnitine
description: Group 1: Carnitine supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study)
arm group label: Carnitine (No antibiotics, No aspirin)
intervention type: Dietary Supplement
intervention name: Choline
description: Group 2: Choline supplement for 2 months, No antibiotics, no aspirin for 3 months (1 month prior and during study)
arm group label: Choline (No Antibiotics, No aspirin)
intervention type: Drug
intervention name: Antibiotics
description: Group 3: Carnitine or Choline for 2 months, antibiotic cocktail (Ciprofloxacin, Flagyl, Vancomycin, and Neomycin) for 1 week
arm group label: Antibiotics
other name: Ciprofloxacin, Flagyl, Vancomycin, and Neomycin
intervention type: Drug
intervention name: Choline and Aspirin
description: 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).
arm group label: Choline and Aspirin
other name: aspirin
intervention type: Drug
intervention name: Carnitine and Aspirin
description: 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).
arm group label: Carnitine and Aspirin
other name: aspirin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Stanley L Hazen, MD, PhD
role: Principal Investigator
affiliation: The Cleveland Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Stanley L Hazen, MD, PhD
investigator title: Primary Investigator
mesh term: Cardiovascular Diseases
mesh term: Aspirin
mesh term: Anti-Bacterial Agents
mesh term: Vancomycin
mesh term: Ciprofloxacin
mesh term: Neomycin
mesh term: Choline
sharing ipd: No