<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/NCT02971046</url>
  </required_header>
  <id_info>
    <org_study_id>1000053342</org_study_id>
    <nct_id>NCT02971046</nct_id>
  </id_info>
  <brief_title>Glutathione (GSH) Synthesis in Healthy School-aged Children and Healthy Young and Old Adults</brief_title>
  <official_title>Glutathione (GSH) Synthesis in Response to Graded Protein Intakes: a Functional Measure of Protein Requirement in Healthy School-aged Children and Healthy Young and Old Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Hospital for Sick Children</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Hospital for Sick Children</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To measure the fractional and absolute synthesis rates of GSH, an antioxidant that protects&#xD;
      cells from damage, in the erythrocytes of healthy school-aged children, young adults and old&#xD;
      adults in response to graded intakes of protein in order to determine if increasing the&#xD;
      protein intake above the current recommended DRI produces increases in the GSH synthesis&#xD;
      rates in erythrocytes of these individuals. Participants will consume specially formulated&#xD;
      diets with varying protein levels.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current dietary reference intake (DRI) recommendations for protein in children (6-11&#xD;
      years old) and adults (&gt;19 years old) are based on nitrogen balance data and set at a mean&#xD;
      (EAR) of 0.76 and 0.66 g/kg/day respectively and population safe (RDA) recommendation of 0.95&#xD;
      and 0.80 g/kg/day respectively. Using the indicator amino oxidation (IAAO) method we&#xD;
      estimated higher protein requirements in these populations. This suggests that current&#xD;
      recommendations are underestimated. Studies in adults have shown that protein recommendation&#xD;
      set on the basis of nitrogen balance data, while sufficient to maintain nitrogen balance,&#xD;
      does not maintain GSH status.&#xD;
&#xD;
      Glutathione (GSH) is most important intracellular antioxidant and scavenger and its&#xD;
      deficiency has been shown to compromise recovery in acute as well as chronic stressors.&#xD;
      Deficiency of GSH results when protein and/or cysteine intake is inadequate. Inadequate&#xD;
      protein intake in children not only compromises growth, but could increase susceptibility to,&#xD;
      and compromise recovery from regular childhood illness. Similarly, in young and older adults'&#xD;
      inadequate intakes may result in increased oxidative stress and compromised immune function.&#xD;
      Measurement of GSH synthesis provides a functional method whereby the current protein&#xD;
      recommendation can be tested against higher estimates derived using the IAAO method. The&#xD;
      purpose of this study therefore is to measure GSH synthesis in healthy school aged children&#xD;
      (6-11 years), and healthy young (19 - 40 years) and old (60 - 90 years) adults in response to&#xD;
      current recommended protein intakes and in response to protein requirement estimates derived&#xD;
      using the IAAO method.&#xD;
&#xD;
      In healthy school-aged children, each level of protein will be studied over three days. For&#xD;
      two days (adaptation days), participants will eat some low protein foods plus a milkshake&#xD;
      drink. On the study day, participants will consume 8 hourly protein drinks and special&#xD;
      cookies at SickKids. In healthy young and old adults, each level of protein will be studied&#xD;
      over three days. For two days (adaptation days), young adults will eat some low protein foods&#xD;
      plus a milkshake drink. On the one study day, young adults will consume 10 hourly milkshake&#xD;
      diets at SickKids. In old adults, each level of protein will be studied over four days. For&#xD;
      three days (adaptation days), old adults will eat some low protein foods plus a milkshake&#xD;
      drink. On the one study day, old adults will consume 10 hourly milkshake diets at SickKids.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 1, 2020</start_date>
  <completion_date type="Anticipated">November 2023</completion_date>
  <primary_completion_date type="Anticipated">November 2023</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Erythrocyte GSH Fractional synthesis rates</measure>
    <time_frame>up to 24 months</time_frame>
    <description>To measure the fractional synthesis rates of GSH in the erythrocytes of healthy school-aged children and healthy young and old adults in response to graded intakes of protein.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Erythrocyte GSH absolute synthesis</measure>
    <time_frame>up to 24 months</time_frame>
    <description>To determine the absolute synthesis rate of GSH in erythrocyte of healthy school aged children and healthy young and old adults in response to varying protein intakes.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">55</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Protein intake</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Varying protein intakes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>varying protein intakes</intervention_name>
    <description>In healthy school-aged children: Four randomly assigned levels of protein intake in a repeated measured design. The levels of protein intake are 0.95, 1.3,1.55, and 2.0 grams per kilogram of bodyweight per day.&#xD;
In healthy young and old adults: Up to six randomly assigned levels of protein intake in a repeated measured design. The levels of protein intake are : 0.66, 0.8, 1, 1.2, and 1.5 grams per kilogram of bodyweight per day.</description>
    <arm_group_label>Protein intake</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria in:&#xD;
&#xD;
          1. Healthy school-aged children&#xD;
&#xD;
               -  Body weight ≥ 22 kg&#xD;
&#xD;
               -  No history of anemia&#xD;
&#xD;
               -  Willingness to participate&#xD;
&#xD;
          2. Healthy Young Adults&#xD;
&#xD;
               -  Consent provided&#xD;
&#xD;
               -  Aged 19 - 40 years old&#xD;
&#xD;
               -  In good general health as evidenced by medical history, physical health and blood&#xD;
                  draw&#xD;
&#xD;
               -  Fasting blood glucose, hemoglobin A1c (HbA1c), urea, creatinine, vitamin-B6,&#xD;
                  vitamin-B12 and folate levels within normal ranges for age.&#xD;
&#xD;
               -  Willingness to participate in the study.&#xD;
&#xD;
               -  BMI &lt;25 kg/m2.&#xD;
&#xD;
          3. Healthy Old Adults&#xD;
&#xD;
               -  Consent provided&#xD;
&#xD;
               -  Aged 60- 90 years old&#xD;
&#xD;
               -  In good general health as evidenced by medical history, physical health and blood&#xD;
                  draw&#xD;
&#xD;
               -  Fasting blood glucose, hemoglobin A1c (HbA1c), urea, creatinine, vitamin-B6,&#xD;
                  vitamin-B12 and folate levels within normal ranges for age.&#xD;
&#xD;
               -  Willingness to participate in the study.&#xD;
&#xD;
               -  BMI &lt;30 kg/m2.&#xD;
&#xD;
        Exclusion Criteria in:&#xD;
&#xD;
          1. Healthy school-aged children&#xD;
&#xD;
               -  HIV&#xD;
&#xD;
               -  Diabetes&#xD;
&#xD;
               -  Anaemia&#xD;
&#xD;
               -  Significant weight loss within 30 days of study&#xD;
&#xD;
               -  On weight loss diets&#xD;
&#xD;
               -  Body weight less that 22kg&#xD;
&#xD;
               -  Inability to tolerate diet&#xD;
&#xD;
               -  Unwilling to have blood drawn&#xD;
&#xD;
          2. Healthy Young and Old Adults:&#xD;
&#xD;
               -  Presence of chronic disease and/or acute illness known to affect GSH and/or&#xD;
                  protein/amino acid metabolism (e.g. HIV, diabetes, cancer, liver or kidney&#xD;
                  disease, acute cold or flu).&#xD;
&#xD;
               -  Anemia (15 - 20% outside lower limit of normal lab reference ranges)&#xD;
&#xD;
               -  Taking medications known to affect GSH and/or protein/AA metabolism (e.g.&#xD;
                  acetaminophen, steroids).&#xD;
&#xD;
               -  Significant weight loss during the past month or consumption of weight reducing&#xD;
                  diets.&#xD;
&#xD;
               -  Significant caffeine consumption (&gt;2 cups per day).&#xD;
&#xD;
               -  Significant consumption of alcohol (&gt;1 drink per day i.e. 1 beer or ½ glass of&#xD;
                  wine).&#xD;
&#xD;
               -  Inability to tolerate the diet&#xD;
&#xD;
               -  Unwilling to have blood drawn from a venous access during the isotope infusion&#xD;
                  day.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Glenda Courtney-Martin, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Academic &amp;Clinical Specialist</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alyssa Paoletti, BSc, MSc</last_name>
    <phone>416-813-7454</phone>
    <email>alyssa.paoletti@sickkids.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mahroukh Rafii, BSc</last_name>
    <phone>416-813-7454</phone>
    <email>mahroukh.rafii@sickkids.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Hospital for Sick Children</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sylwia Szwiega, BSc, MSc</last_name>
      <phone>416-813-7454</phone>
      <email>sylwia.szwiega@sickkids.ca</email>
    </contact>
    <contact_backup>
      <last_name>Mahroukh Rafii, BSc</last_name>
      <phone>416-813-7454</phone>
      <email>mahroukh.rafii@sickkids.ca</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 11, 2016</study_first_submitted>
  <study_first_submitted_qc>November 18, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <last_update_submitted>May 31, 2023</last_update_submitted>
  <last_update_submitted_qc>May 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Hospital for Sick Children</investigator_affiliation>
    <investigator_full_name>Glenda Courtney-Martin</investigator_full_name>
    <investigator_title>Academic &amp;Clinical Specialist, Project Investigator</investigator_title>
  </responsible_party>
  <keyword>healthy children</keyword>
  <keyword>protein</keyword>
  <keyword>glutathione</keyword>
  <keyword>protein requirement</keyword>
  <keyword>healthy young adults</keyword>
  <keyword>healthy adults over 60 years of age</keyword>
  <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/NCT02971046
org study id: 1000053342
nct id: NCT02971046
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To measure the fractional and absolute synthesis rates of GSH, an antioxidant that protects
      cells from damage, in the erythrocytes of healthy school-aged children, young adults and old
      adults in response to graded intakes of protein in order to determine if increasing the
      protein intake above the current recommended DRI produces increases in the GSH synthesis
      rates in erythrocytes of these individuals. Participants will consume specially formulated
      diets with varying protein levels.
The current dietary reference intake (DRI) recommendations for protein in children (6-11
      years old) and adults (>19 years old) are based on nitrogen balance data and set at a mean
      (EAR) of 0.76 and 0.66 g/kg/day respectively and population safe (RDA) recommendation of 0.95
      and 0.80 g/kg/day respectively. Using the indicator amino oxidation (IAAO) method we
      estimated higher protein requirements in these populations. This suggests that current
      recommendations are underestimated. Studies in adults have shown that protein recommendation
      set on the basis of nitrogen balance data, while sufficient to maintain nitrogen balance,
      does not maintain GSH status.

      Glutathione (GSH) is most important intracellular antioxidant and scavenger and its
      deficiency has been shown to compromise recovery in acute as well as chronic stressors.
      Deficiency of GSH results when protein and/or cysteine intake is inadequate. Inadequate
      protein intake in children not only compromises growth, but could increase susceptibility to,
      and compromise recovery from regular childhood illness. Similarly, in young and older adults'
      inadequate intakes may result in increased oxidative stress and compromised immune function.
      Measurement of GSH synthesis provides a functional method whereby the current protein
      recommendation can be tested against higher estimates derived using the IAAO method. The
      purpose of this study therefore is to measure GSH synthesis in healthy school aged children
      (6-11 years), and healthy young (19 - 40 years) and old (60 - 90 years) adults in response to
      current recommended protein intakes and in response to protein requirement estimates derived
      using the IAAO method.

      In healthy school-aged children, each level of protein will be studied over three days. For
      two days (adaptation days), participants will eat some low protein foods plus a milkshake
      drink. On the study day, participants will consume 8 hourly protein drinks and special
      cookies at SickKids. In healthy young and old adults, each level of protein will be studied
      over three days. For two days (adaptation days), young adults will eat some low protein foods
      plus a milkshake drink. On the one study day, young adults will consume 10 hourly milkshake
      diets at SickKids. In old adults, each level of protein will be studied over four days. For
      three days (adaptation days), old adults will eat some low protein foods plus a milkshake
      drink. On the one study day, old adults will consume 10 hourly milkshake diets at SickKids.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Erythrocyte GSH Fractional synthesis rates
time frame: up to 24 months
description: To measure the fractional synthesis rates of GSH in the erythrocytes of healthy school-aged children and healthy young and old adults in response to graded intakes of protein.
measure: Erythrocyte GSH absolute synthesis
time frame: up to 24 months
description: To determine the absolute synthesis rate of GSH in erythrocyte of healthy school aged children and healthy young and old adults in response to varying protein intakes.
arm group label: Protein intake
arm group type: Experimental
description: Varying protein intakes.
intervention type: Other
intervention name: varying protein intakes
description: In healthy school-aged children: Four randomly assigned levels of protein intake in a repeated measured design. The levels of protein intake are 0.95, 1.3,1.55, and 2.0 grams per kilogram of bodyweight per day.
In healthy young and old adults: Up to six randomly assigned levels of protein intake in a repeated measured design. The levels of protein intake are : 0.66, 0.8, 1, 1.2, and 1.5 grams per kilogram of bodyweight per day.
arm group label: Protein intake
criteria: 
gender: All
minimum age: 6 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Glenda Courtney-Martin, PhD
role: Principal Investigator
affiliation: Academic &Clinical Specialist
last name: Alyssa Paoletti, BSc, MSc
phone: 416-813-7454
email: alyssa.paoletti@sickkids.ca
last name: Mahroukh Rafii, BSc
phone: 416-813-7454
email: mahroukh.rafii@sickkids.ca
facility: 
status: Recruiting
contact: 
contact backup: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: The Hospital for Sick Children
investigator full name: Glenda Courtney-Martin
investigator title: Academic &Clinical Specialist, Project Investigator
sharing ipd: No