<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/NCT01725503</url>
  </required_header>
  <id_info>
    <org_study_id>10-005</org_study_id>
    <nct_id>NCT01725503</nct_id>
  </id_info>
  <brief_title>Creatine Kinetics, Synthesis From Glycine and Response to Creatine and Amino Acid Supplement in Healthy Humans</brief_title>
  <official_title>Creatine Metabolism in Humans:Effect of Creatine and Amino Acid Supplement</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 goal of the present study is to quantify the rate of synthesis of creatine in healthy&#xD;
      controls and endurance trained subjects. In addition, the effect of oral creatine supplement&#xD;
      for seven days on creatine kinetics will be examined.&#xD;
&#xD;
      Ten healthy controls (age 20-35 years) and ten endurance trained subjects will be recruited&#xD;
      by advertisement. Endurance trained subjects will be recruited from health clubs. They will&#xD;
      be screened for absence of any chronic disease (history, physical examination, CBC, metabolic&#xD;
      and liver panel, urinalysis). A DEXA measurement will be done to quantify whole body skeletal&#xD;
      muscle mass.&#xD;
&#xD;
      For five (5) days prior to the study, they will be placed on a creatine-free (essentially&#xD;
      meat-free) diet. Dietary compliance will be ensured by repeated communication with the&#xD;
      subject, by nurse coordinator and the CRU Nutritionist. Subject will maintain daily record of&#xD;
      the food intake for validation. On the last day, i.e. 24 hours prior to the tracer study,&#xD;
      subject will collect the 24 hours urine sample and bring it to the CRU on the day of the&#xD;
      study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Creatine and phosphocreatine are the major intracellular buffers for adenosine triphosphate.&#xD;
      They also function as the energy shuttle for high energy phosphate from the mitochondrial&#xD;
      site of production to the cytoplasmic site of utilization. In addition, creatine has been&#xD;
      shown to affect satellite cell proliferation and differentiation and increase cell mitotic&#xD;
      activity during compensatory hypertrophy in rat skeletal muscle. Creatine is synthesized from&#xD;
      three amino acids: glycine, arginine and methionine. Although creatine metabolism has been&#xD;
      studied extensively in the rat, the data regarding the kinetics of creatine and their&#xD;
      regulation in humans are limited. This is in part due to a large and slow turning over pool&#xD;
      of creatine and lack of good tracer methods. Using a recently developed stable isotopic&#xD;
      tracer method (by us), we propose to quantify the rate of synthesis of creatine and its&#xD;
      regulation in healthy subjects and in those with large skeletal muscle mass as a result of&#xD;
      endurance training. In addition, the response to oral creatine administration on creatine&#xD;
      kinetics will be quantified. The site of regulation will be identified by the relative rate&#xD;
      of appearance of tracer glycine in guanidinoacetic acid and creatine. It is hypothesized that&#xD;
      the fractional rate of synthesis of creatine will be higher in endurance trained subjects,&#xD;
      and that creatine will suppress the rate of synthesis of creatine. Since creatine is critical&#xD;
      for the maintenance of skeletal muscle mass and satellite cell proliferation, these data will&#xD;
      provide the normative physiological data for future studies of subjects with manifest&#xD;
      sarcopenia, such as aging, and those with chronic diseases, e.g. cirrhosis of liver. These&#xD;
      data will form the basis for the studies of creatine metabolism in neurodegenerative&#xD;
      disorders where creatine is being increasingly used as a therapeutic agent.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2010</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">June 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quantification of creatine synthesis in healthy subjects</measure>
    <time_frame>12/31/2012</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of creatine supplement on the rate of creatine synthesis</measure>
    <time_frame>12/31/2012</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Creatine Synthesis in Healthy Subjects</condition>
  <arm_group>
    <arm_group_label>Creatine and amino acid supplement</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Creatine and Amino Acid supplement</intervention_name>
    <arm_group_label>Creatine and amino acid supplement</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy controls and endurance trained subjects&#xD;
&#xD;
          -  Both males and females will be studied.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  any illness&#xD;
&#xD;
          -  on any medications and/or supplements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Satish Kalhan, MD</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>January 2014</verification_date>
  <study_first_submitted>November 8, 2012</study_first_submitted>
  <study_first_submitted_qc>November 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <last_update_submitted>January 29, 2014</last_update_submitted>
  <last_update_submitted_qc>January 29, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 30, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Satish Kalhan</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>creatine synthesis</keyword>
  <!-- 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/NCT01725503
org study id: 10-005
nct id: NCT01725503
lead sponsor: 
has dmc: No
The goal of the present study is to quantify the rate of synthesis of creatine in healthy
      controls and endurance trained subjects. In addition, the effect of oral creatine supplement
      for seven days on creatine kinetics will be examined.

      Ten healthy controls (age 20-35 years) and ten endurance trained subjects will be recruited
      by advertisement. Endurance trained subjects will be recruited from health clubs. They will
      be screened for absence of any chronic disease (history, physical examination, CBC, metabolic
      and liver panel, urinalysis). A DEXA measurement will be done to quantify whole body skeletal
      muscle mass.

      For five (5) days prior to the study, they will be placed on a creatine-free (essentially
      meat-free) diet. Dietary compliance will be ensured by repeated communication with the
      subject, by nurse coordinator and the CRU Nutritionist. Subject will maintain daily record of
      the food intake for validation. On the last day, i.e. 24 hours prior to the tracer study,
      subject will collect the 24 hours urine sample and bring it to the CRU on the day of the
      study.
Creatine and phosphocreatine are the major intracellular buffers for adenosine triphosphate.
      They also function as the energy shuttle for high energy phosphate from the mitochondrial
      site of production to the cytoplasmic site of utilization. In addition, creatine has been
      shown to affect satellite cell proliferation and differentiation and increase cell mitotic
      activity during compensatory hypertrophy in rat skeletal muscle. Creatine is synthesized from
      three amino acids: glycine, arginine and methionine. Although creatine metabolism has been
      studied extensively in the rat, the data regarding the kinetics of creatine and their
      regulation in humans are limited. This is in part due to a large and slow turning over pool
      of creatine and lack of good tracer methods. Using a recently developed stable isotopic
      tracer method (by us), we propose to quantify the rate of synthesis of creatine and its
      regulation in healthy subjects and in those with large skeletal muscle mass as a result of
      endurance training. In addition, the response to oral creatine administration on creatine
      kinetics will be quantified. The site of regulation will be identified by the relative rate
      of appearance of tracer glycine in guanidinoacetic acid and creatine. It is hypothesized that
      the fractional rate of synthesis of creatine will be higher in endurance trained subjects,
      and that creatine will suppress the rate of synthesis of creatine. Since creatine is critical
      for the maintenance of skeletal muscle mass and satellite cell proliferation, these data will
      provide the normative physiological data for future studies of subjects with manifest
      sarcopenia, such as aging, and those with chronic diseases, e.g. cirrhosis of liver. These
      data will form the basis for the studies of creatine metabolism in neurodegenerative
      disorders where creatine is being increasingly used as a therapeutic agent.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Quantification of creatine synthesis in healthy subjects
time frame: 12/31/2012
measure: Effect of creatine supplement on the rate of creatine synthesis
time frame: 12/31/2012
arm group label: Creatine and amino acid supplement
arm group type: Experimental
intervention type: Dietary Supplement
intervention name: Creatine and Amino Acid supplement
arm group label: Creatine and amino acid supplement
criteria: 
gender: All
minimum age: 20 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Satish Kalhan, MD
role: Principal Investigator
affiliation: The Cleveland Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Satish Kalhan
investigator title: Principal Investigator