<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/NCT02202876</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00060962</org_study_id>
    <nct_id>NCT02202876</nct_id>
  </id_info>
  <brief_title>Redox Imbalance and the Development of Cystic Fibrosis Diabetes</brief_title>
  <acronym>Redoxy</acronym>
  <official_title>Redox Imbalance and the Development of Cystic Fibrosis Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cystic Fibrosis Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</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>
      Cystic fibrosis-related diabetes (CFRD) occurs in almost 20% of teens and 50% of adults. The&#xD;
      investigators' long term goal is to determine the cause of CFRD in order to translate this&#xD;
      knowledge into therapies aimed at preventing CFRD. Since CFRD and type 2 diabetes share&#xD;
      several clinical features and since oxidative stress is a key factor in the development of&#xD;
      type 2 diabetes, the investigators explored the role of oxidative stress in CFRD. The&#xD;
      investigators discovered a unique CF biochemical signature that they believe could be&#xD;
      implicated in the development of CFRD. The investigators found that glucose ingestion in CF&#xD;
      teens and young adults causes an acute and profound systemic redox imbalance to the oxidizing&#xD;
      state. The degree of redox imbalance was quite severe and would be expected to damage the&#xD;
      insulin producing cells as these cells are particularly vulnerable to oxidative stress. Thus,&#xD;
      these findings could prove to be a critical factor in the pathogenesis of CFRD. This proposal&#xD;
      will test the hypothesis that glucose-induced redox imbalance is an intrinsic, metabolic&#xD;
      defect in CF. In addition, because CF people are required to consume a high calorie diet to&#xD;
      maintain their weight, the investigators also hypothesize that certain high caloric foods&#xD;
      will recapitulate the redox imbalance induced by ingesting glucose and thus hasten the&#xD;
      development of CFRD. Specifically, the investigators aim to:&#xD;
&#xD;
        -  Determine whether young children with CF have glucose-induced redox imbalance&#xD;
&#xD;
        -  Determine whether eating a meal with a high glycemic index induces acute redox imbalance&#xD;
&#xD;
        -  Determine whether commonly consumed beverages containing simple sugars (i.e., soda or&#xD;
           fruit juice) induce acute redox imbalance&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim 1: Three groups of subjects will be evaluated: 1. 27 CF children with class I-III&#xD;
      mutations aged 1 to 9 years with normal glucose tolerance (NGT), 2. 27 age-matched controls&#xD;
      with NGT, and 3. 15 CF children with class IV-VI CF transmembrane conductance regulator&#xD;
      (CFTR) mutations ages 1 to 9 years. After obtaining informed consent from the parents,&#xD;
      subjects will undergo an overnight fast with nothing to eat or drink except water for 10&#xD;
      hours. The children will be asked to withhold all short-acting bronchodilators prior to the&#xD;
      start of the study visit and to withhold all long-acting bronchodilators for a minimum of ten&#xD;
      hours prior to the start of the study visit. Prior to the study visit, parents will be given&#xD;
      a three-day diet journal in which they will record in detail everything each child consumes&#xD;
      during the recording period. Details include amount of food or drink and brand names as well&#xD;
      as pancreatic enzyme replacement therapy (PERT) dose given with each meal or snack. The&#xD;
      recording period will include two week days and one weekend day. The children will have an&#xD;
      intravenous (IV) line placed and blood drawn for measurement of plasma glucose, insulin, and&#xD;
      cysteine (CyS)/cystine (CySS) redox state. Then the child will be given 1.75 gm/kg to a&#xD;
      maximum of 75 gm of an oral glucose solution to drink and will be coached to drink it within&#xD;
      10 minutes. Blood will be drawn 30 minutes after glucose ingestion for repeat measures of&#xD;
      glucose, insulin, and redox status. Blood will be drawn 2 hours after glucose ingestion for&#xD;
      repeat measures of glucose, insulin, and redox status. Subjects who completed the protocol&#xD;
      will be approached to reconsent and repeat the protocol annually to track their level of&#xD;
      glucose intolerance and monitor for conversion to CF Diabetes. For children who are able,&#xD;
      exhaled breath condensate (EBC) will also be collected prior to the oral glucose tolerance&#xD;
      test (OGTT) and immediately following completion of the 2 hour blood draw. EBC will be&#xD;
      analyzed for Cys/CySS redox coupling.&#xD;
&#xD;
      Aim 2a: Forty-four CF subjects 12 years of age or older with NGT or impaired glucose will&#xD;
      undergo a meal challenge with half randomized to receive a test meal with a high glycemic&#xD;
      index and half a meal with a low index. Subjects will fast overnight for 10 hours taking&#xD;
      nothing to eat or drink except water. Subjects will be instructed to withhold all&#xD;
      short-acting bronchodilators for a minimum of four hours prior to the start of the study&#xD;
      visit and withhold all long-acting bronchodilators for a minimum of ten hours prior to the&#xD;
      start of the study visit. Following informed consent, participants will first undergo&#xD;
      indirect calorimetry for determination of resting metabolic rate and substrate oxidation;&#xD;
      this will occur only in participants 16 years old and older. An intravenous line (IV) will&#xD;
      then be inserted; and an iPro sensor placed for continuous glucose monitoring (CGM);&#xD;
      placement of the CGM will be optional as our experience with this protocol indicates that&#xD;
      some CF patients will not volunteer for CGM placement but will for IV placement. If the iPro&#xD;
      sensor is inserted; it must be in place for a minimum of 60 minutes prior to the baseline&#xD;
      blood draw to allow the iPro sensor device to detect interstitial glucose levels accurately.&#xD;
      Blood will be drawn for measurement of glucose, insulin, Cys/CySS redox status,&#xD;
      acylcarnitine, total carnitine, proteomics and metabolomics analysis on subjects 16 years&#xD;
      older and older. For the subjects 12 years old to 15 years old, blood will be drawn for&#xD;
      measurement of glucose, insulin, Cys/CySS redox status, and proteomics. The subject will then&#xD;
      be instructed to eat one of two tests meals in ten minutes. Subjects must complete the meal.&#xD;
      Meals will be isocaloric breakfasts with one meal having a high glycemic index and one a low.&#xD;
      The nutrient composition of each meal will be 10 kcal per kg, 50% kcal from carbohydrates,&#xD;
      20% kcal from protein, and 30% kcal from fat. Blood will be drawn for repeat measures of&#xD;
      glucose, insulin, CyS/CySS redox state1, 2, and 3 hours after the test meal on all subjects.&#xD;
      Blood will be drawn for proteomics at base line and at 3 hours on all subjects. Additional&#xD;
      blood will be drawn at baseline and 2 hrs after the meal for measurement of acylcarnitine,&#xD;
      total carnitine,and metabolomics and biomarkers related to fatty acid metabolism on subjects&#xD;
      16 years old and older. Following the 3 hour blood draw, the IV line and iPro sensor, if&#xD;
      placed, will be discontinued. A whole-body dual energy X-ray absorptiometry (DEXA) scan will&#xD;
      be administered at the completion of the 3 hr blood draw for analysis of body composition;&#xD;
      this test will be performed only on those subjects 16 years old and older. Female&#xD;
      participants will be required to complete a urine pregnancy test prior to the DEXA scan to&#xD;
      confirm a non-pregnant status. If the participant's urine pregnancy test shows a positive&#xD;
      pregnancy, the DEXA scan will not be completed. Following the DEXA scan, the subject will be&#xD;
      discharged home. Prior to their study visit, participants16 years and older will be given&#xD;
      instructions to complete a 3-day food record for estimation of usual dietary intake as part&#xD;
      of their standard CF care.&#xD;
&#xD;
      Aim 2b. Forty-four CF subjects 12 years of age or older with NGT or impaired glucose will&#xD;
      initially undergo a test beverage challenge, using a test soda that contains 60% fructose and&#xD;
      40% glucose or fruit juice that contains a combination fructose, glucose, and sucrose at a&#xD;
      dose of 1.75 grams per kilogram body weight to a maximum of 75 grams. One to four weeks later&#xD;
      all subjects will have an OGTT, that is, ingestion of oral glucose solution at a dose of 1.75&#xD;
      grams per kilogram to a maximum of 75 grams. Of the 44 subjects drinking the test beverage,&#xD;
      twenty-two will be administered the soda, and twenty-two will be administered fruit juice&#xD;
      Subjects will fast overnight for 10 hours taking nothing to eat or drink except water.&#xD;
      Subjects will be instructed to withhold all short-acting bronchodilators for a minimum of&#xD;
      four hours prior to the start of the study visit and withhold all long-acting bronchodilators&#xD;
      for a minimum of ten hours prior to the start of the study visit. After obtaining informed&#xD;
      consent participants will have an intravenous line (IV) inserted. Blood will be drawn for&#xD;
      measurements of glucose, insulin, and Cys/CySS redox status at baseline or zero minutes. The&#xD;
      subject will then be instructed to drink a test beverage, either a test soda or fruit juice,&#xD;
      in ten minutes that was prepared by the research bio-nutritionist. Repeat blood samples will&#xD;
      be drawn for measures of glucose, insulin, and CyS/CySS redox state ½ hour, 1 hour and 2&#xD;
      hours from the initial consumption of the test beverage drink. During the study visit a&#xD;
      beverage intake questionnaire will be administered to assess the patient's overall intake of&#xD;
      sweetened beverages. At the completion of the visit the participant will be scheduled for a&#xD;
      subsequent visit in one to four weeks for repeat testing using the same guidelines as above,&#xD;
      but the test drink to be used is a glucose solution (glucola) used for the standard OGTT. The&#xD;
      75 gram glucola drink will be used for testing; the dose administered will be determined by&#xD;
      multiplying the patients weight x 1.75 grams; the dose administered is not to exceed 75&#xD;
      grams. Subjects must consume all of the drink. Blood samples will be drawn at baseline (prior&#xD;
      to glucola intake) and then repeat blood samples will be drawn for measures of glucose,&#xD;
      insulin, and CyS/CySS redox state ½ hour, 1 hour and 2 hours from the initial consumption of&#xD;
      the glucola drink. Insertion of the continuous glucose monitor is optional during the test&#xD;
      beverage challenge and the redox OGTT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2014</start_date>
  <completion_date type="Actual">September 9, 2018</completion_date>
  <primary_completion_date type="Actual">September 9, 2018</primary_completion_date>
  <phase>N/A</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>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acute oxidation</measure>
    <time_frame>Up to three hours</time_frame>
    <description>cysteine/cysteine ratio</description>
  </primary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Diabetes Mellitus, Type 2</condition>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Aim 1: Children with Cystic Fibrosis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cystic Fibrosis children aged 1 to 9 years with normal glucose tolerance receiving Oral Glucose Tolerance Test</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aim 1: Control Children</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Children with out Cystic Fibrosis aged 1 to 9 years controls with normal glucose tolerance receiving Oral Glucose Tolerance Test</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aim 2a: Teens with Cystic Fibrosis - High Glycemic Meal</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cystic Fibrosis subjects 12 years of age or older with normal glucose tolerance eating High Glycemic Index Meal</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aim 2a: Teens with Cystic Fibrosis - Low Glycemic Meal</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cystic Fibrosis subjects 12 years of age or older with normal glucose tolerance eating Low Glycemic Index Meal</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aim 2b: Cystic Fibrosis Consuming Test Soda</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants with Cystic Fibrosis 12 years of age or older with normal glucose tolerance or impaired glucose tolerance consuming a test beverage of a test soda. A week later these participants will have an Oral Glucose Tolerance Test.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aim 2b: Cystic Fibrosis Consuming Fruit Juice</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants with Cystic Fibrosis 12 years of age or older with normal glucose tolerance or impaired glucose tolerance consuming a test beverage of fruit juice. A week later these participants will have an Oral Glucose Tolerance Test.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Oral Glucose Tolerance Test</intervention_name>
    <description>1.75 gm/kg to a maximum of 75 gm of an oral glucose solution</description>
    <arm_group_label>Aim 1: Children with Cystic Fibrosis</arm_group_label>
    <arm_group_label>Aim 1: Control Children</arm_group_label>
    <arm_group_label>Aim 2b: Cystic Fibrosis Consuming Fruit Juice</arm_group_label>
    <arm_group_label>Aim 2b: Cystic Fibrosis Consuming Test Soda</arm_group_label>
    <other_name>OGTT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High Glycemic Index Meal</intervention_name>
    <description>isocaloric breakfasts - set the high glycemic index to 80&#xD;
The nutrient composition of each meal will be 10 kcal per kg, 50% kcal from carbohydrates, 20% kcal from protein, and 30% kcal from fat</description>
    <arm_group_label>Aim 2a: Teens with Cystic Fibrosis - High Glycemic Meal</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Low Glycemic Index Meal</intervention_name>
    <description>isocaloric breakfasts - set the low glycemic index to 30&#xD;
The nutrient composition of each meal will be 10 kcal per kg, 50% kcal from carbohydrates, 20% kcal from protein, and 30% kcal from fat</description>
    <arm_group_label>Aim 2a: Teens with Cystic Fibrosis - Low Glycemic Meal</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Test Soda</intervention_name>
    <description>Test soda containing 60% fructose and 40% glucose at a dose of 1.75 grams per kilogram body weight to a maximum of 75 grams.</description>
    <arm_group_label>Aim 2b: Cystic Fibrosis Consuming Test Soda</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fruit juice</intervention_name>
    <description>Fruit juice containing a combination fructose, glucose, and sucrose at a dose of 1.75 grams per kilogram body weight to a maximum of 75 grams</description>
    <arm_group_label>Aim 2b: Cystic Fibrosis Consuming Fruit Juice</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Aim 1&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
        For CF children with class I-III mutations&#xD;
&#xD;
          -  CF diagnosed by pilocarpine electrophoresis sweat test and/or CFTR genetic mutation&#xD;
             analysis&#xD;
&#xD;
          -  CFTR mutation analysis showing two Class I to III mutations&#xD;
&#xD;
          -  Aged 1-9 years&#xD;
&#xD;
          -  On a clinically stable medical regimen for at least three weeks&#xD;
&#xD;
          -  No IV or oral antibiotics for a respiratory exacerbation for at least three weeks&#xD;
&#xD;
          -  No hospitalization for at least six weeks&#xD;
&#xD;
        For CF children with class IV-VI mutations&#xD;
&#xD;
          -  CF diagnosed by pilocarpine electrophoresis sweat test and/or CFTR genetic mutation&#xD;
             analysis&#xD;
&#xD;
          -  CFTR mutation analysis showing at least one Class IV-VI mutation&#xD;
&#xD;
          -  Aged 1-9 years&#xD;
&#xD;
          -  On a clinically stable medical regimen for at least three weeks&#xD;
&#xD;
          -  No IV or oral antibiotics for a respiratory exacerbation for at least three weeks&#xD;
&#xD;
          -  No hospitalization for at least six weeks&#xD;
&#xD;
          -  Not taking pancreatic enzyme replacement therapy&#xD;
&#xD;
        For age-matched controls&#xD;
&#xD;
          -  No acute illness for at least six weeks&#xD;
&#xD;
          -  Never been hospitalized except at birth following a full term delivery&#xD;
&#xD;
          -  Aged 1 to 9 years&#xD;
&#xD;
          -  Without any chronic illness requiring prescription medications&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or past diagnosis of CFRD (for CF children)&#xD;
&#xD;
          -  Parents unwilling to have an IV inserted for blood draws&#xD;
&#xD;
        Aim 2a&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  CF diagnosed by pilocarpine electrophoresis sweat test and/or CFTR genetic mutation&#xD;
             analysis&#xD;
&#xD;
          -  CFTR mutation analysis showing two Class I to III mutations&#xD;
&#xD;
          -  Aged 12 years or older&#xD;
&#xD;
          -  On a clinically stable medical regimen for at least three weeks&#xD;
&#xD;
          -  No IV or oral antibiotics for a respiratory exacerbation for at least three weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or past diagnosis of CFRD&#xD;
&#xD;
          -  Allergy or intolerance to egg or dairy products&#xD;
&#xD;
        Aim 2b&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  CF diagnosed by pilocarpine electrophoresis sweat test and/or CFTR genetic mutation&#xD;
             analysis&#xD;
&#xD;
          -  CFTR mutation analysis showing two Class I to III mutations&#xD;
&#xD;
          -  Aged 12 years or older&#xD;
&#xD;
          -  On a clinically stable medical regimen for at least three weeks&#xD;
&#xD;
          -  No IV or oral antibiotics for a respiratory exacerbation for at least three weeks&#xD;
&#xD;
          -  Subjects who have or have not completed the redox meal challenge are allowed to&#xD;
             participate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or past diagnosis of CFRD&#xD;
&#xD;
          -  Allergy or intolerance to any component of the test beverage (i.e., soda, fruit juice)&#xD;
             and glucola&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arlene Stecenko, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta and Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>July 25, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>June 1, 2020</last_update_submitted>
  <last_update_submitted_qc>June 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Arlene Stecenko</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_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/NCT02202876
org study id: IRB00060962
nct id: NCT02202876
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Cystic fibrosis-related diabetes (CFRD) occurs in almost 20% of teens and 50% of adults. The
      investigators' long term goal is to determine the cause of CFRD in order to translate this
      knowledge into therapies aimed at preventing CFRD. Since CFRD and type 2 diabetes share
      several clinical features and since oxidative stress is a key factor in the development of
      type 2 diabetes, the investigators explored the role of oxidative stress in CFRD. The
      investigators discovered a unique CF biochemical signature that they believe could be
      implicated in the development of CFRD. The investigators found that glucose ingestion in CF
      teens and young adults causes an acute and profound systemic redox imbalance to the oxidizing
      state. The degree of redox imbalance was quite severe and would be expected to damage the
      insulin producing cells as these cells are particularly vulnerable to oxidative stress. Thus,
      these findings could prove to be a critical factor in the pathogenesis of CFRD. This proposal
      will test the hypothesis that glucose-induced redox imbalance is an intrinsic, metabolic
      defect in CF. In addition, because CF people are required to consume a high calorie diet to
      maintain their weight, the investigators also hypothesize that certain high caloric foods
      will recapitulate the redox imbalance induced by ingesting glucose and thus hasten the
      development of CFRD. Specifically, the investigators aim to:

        -  Determine whether young children with CF have glucose-induced redox imbalance

        -  Determine whether eating a meal with a high glycemic index induces acute redox imbalance

        -  Determine whether commonly consumed beverages containing simple sugars (i.e., soda or
           fruit juice) induce acute redox imbalance
Aim 1: Three groups of subjects will be evaluated: 1. 27 CF children with class I-III
      mutations aged 1 to 9 years with normal glucose tolerance (NGT), 2. 27 age-matched controls
      with NGT, and 3. 15 CF children with class IV-VI CF transmembrane conductance regulator
      (CFTR) mutations ages 1 to 9 years. After obtaining informed consent from the parents,
      subjects will undergo an overnight fast with nothing to eat or drink except water for 10
      hours. The children will be asked to withhold all short-acting bronchodilators prior to the
      start of the study visit and to withhold all long-acting bronchodilators for a minimum of ten
      hours prior to the start of the study visit. Prior to the study visit, parents will be given
      a three-day diet journal in which they will record in detail everything each child consumes
      during the recording period. Details include amount of food or drink and brand names as well
      as pancreatic enzyme replacement therapy (PERT) dose given with each meal or snack. The
      recording period will include two week days and one weekend day. The children will have an
      intravenous (IV) line placed and blood drawn for measurement of plasma glucose, insulin, and
      cysteine (CyS)/cystine (CySS) redox state. Then the child will be given 1.75 gm/kg to a
      maximum of 75 gm of an oral glucose solution to drink and will be coached to drink it within
      10 minutes. Blood will be drawn 30 minutes after glucose ingestion for repeat measures of
      glucose, insulin, and redox status. Blood will be drawn 2 hours after glucose ingestion for
      repeat measures of glucose, insulin, and redox status. Subjects who completed the protocol
      will be approached to reconsent and repeat the protocol annually to track their level of
      glucose intolerance and monitor for conversion to CF Diabetes. For children who are able,
      exhaled breath condensate (EBC) will also be collected prior to the oral glucose tolerance
      test (OGTT) and immediately following completion of the 2 hour blood draw. EBC will be
      analyzed for Cys/CySS redox coupling.

      Aim 2a: Forty-four CF subjects 12 years of age or older with NGT or impaired glucose will
      undergo a meal challenge with half randomized to receive a test meal with a high glycemic
      index and half a meal with a low index. Subjects will fast overnight for 10 hours taking
      nothing to eat or drink except water. Subjects will be instructed to withhold all
      short-acting bronchodilators for a minimum of four hours prior to the start of the study
      visit and withhold all long-acting bronchodilators for a minimum of ten hours prior to the
      start of the study visit. Following informed consent, participants will first undergo
      indirect calorimetry for determination of resting metabolic rate and substrate oxidation;
      this will occur only in participants 16 years old and older. An intravenous line (IV) will
      then be inserted; and an iPro sensor placed for continuous glucose monitoring (CGM);
      placement of the CGM will be optional as our experience with this protocol indicates that
      some CF patients will not volunteer for CGM placement but will for IV placement. If the iPro
      sensor is inserted; it must be in place for a minimum of 60 minutes prior to the baseline
      blood draw to allow the iPro sensor device to detect interstitial glucose levels accurately.
      Blood will be drawn for measurement of glucose, insulin, Cys/CySS redox status,
      acylcarnitine, total carnitine, proteomics and metabolomics analysis on subjects 16 years
      older and older. For the subjects 12 years old to 15 years old, blood will be drawn for
      measurement of glucose, insulin, Cys/CySS redox status, and proteomics. The subject will then
      be instructed to eat one of two tests meals in ten minutes. Subjects must complete the meal.
      Meals will be isocaloric breakfasts with one meal having a high glycemic index and one a low.
      The nutrient composition of each meal will be 10 kcal per kg, 50% kcal from carbohydrates,
      20% kcal from protein, and 30% kcal from fat. Blood will be drawn for repeat measures of
      glucose, insulin, CyS/CySS redox state1, 2, and 3 hours after the test meal on all subjects.
      Blood will be drawn for proteomics at base line and at 3 hours on all subjects. Additional
      blood will be drawn at baseline and 2 hrs after the meal for measurement of acylcarnitine,
      total carnitine,and metabolomics and biomarkers related to fatty acid metabolism on subjects
      16 years old and older. Following the 3 hour blood draw, the IV line and iPro sensor, if
      placed, will be discontinued. A whole-body dual energy X-ray absorptiometry (DEXA) scan will
      be administered at the completion of the 3 hr blood draw for analysis of body composition;
      this test will be performed only on those subjects 16 years old and older. Female
      participants will be required to complete a urine pregnancy test prior to the DEXA scan to
      confirm a non-pregnant status. If the participant's urine pregnancy test shows a positive
      pregnancy, the DEXA scan will not be completed. Following the DEXA scan, the subject will be
      discharged home. Prior to their study visit, participants16 years and older will be given
      instructions to complete a 3-day food record for estimation of usual dietary intake as part
      of their standard CF care.

      Aim 2b. Forty-four CF subjects 12 years of age or older with NGT or impaired glucose will
      initially undergo a test beverage challenge, using a test soda that contains 60% fructose and
      40% glucose or fruit juice that contains a combination fructose, glucose, and sucrose at a
      dose of 1.75 grams per kilogram body weight to a maximum of 75 grams. One to four weeks later
      all subjects will have an OGTT, that is, ingestion of oral glucose solution at a dose of 1.75
      grams per kilogram to a maximum of 75 grams. Of the 44 subjects drinking the test beverage,
      twenty-two will be administered the soda, and twenty-two will be administered fruit juice
      Subjects will fast overnight for 10 hours taking nothing to eat or drink except water.
      Subjects will be instructed to withhold all short-acting bronchodilators for a minimum of
      four hours prior to the start of the study visit and withhold all long-acting bronchodilators
      for a minimum of ten hours prior to the start of the study visit. After obtaining informed
      consent participants will have an intravenous line (IV) inserted. Blood will be drawn for
      measurements of glucose, insulin, and Cys/CySS redox status at baseline or zero minutes. The
      subject will then be instructed to drink a test beverage, either a test soda or fruit juice,
      in ten minutes that was prepared by the research bio-nutritionist. Repeat blood samples will
      be drawn for measures of glucose, insulin, and CyS/CySS redox state ½ hour, 1 hour and 2
      hours from the initial consumption of the test beverage drink. During the study visit a
      beverage intake questionnaire will be administered to assess the patient's overall intake of
      sweetened beverages. At the completion of the visit the participant will be scheduled for a
      subsequent visit in one to four weeks for repeat testing using the same guidelines as above,
      but the test drink to be used is a glucose solution (glucola) used for the standard OGTT. The
      75 gram glucola drink will be used for testing; the dose administered will be determined by
      multiplying the patients weight x 1.75 grams; the dose administered is not to exceed 75
      grams. Subjects must consume all of the drink. Blood samples will be drawn at baseline (prior
      to glucola intake) and then repeat blood samples will be drawn for measures of glucose,
      insulin, and CyS/CySS redox state ½ hour, 1 hour and 2 hours from the initial consumption of
      the glucola drink. Insertion of the continuous glucose monitor is optional during the test
      beverage challenge and the redox OGTT.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Acute oxidation
time frame: Up to three hours
description: cysteine/cysteine ratio
arm group label: Aim 1: Children with Cystic Fibrosis
arm group type: Active Comparator
description: Cystic Fibrosis children aged 1 to 9 years with normal glucose tolerance receiving Oral Glucose Tolerance Test
arm group label: Aim 1: Control Children
arm group type: Active Comparator
description: Children with out Cystic Fibrosis aged 1 to 9 years controls with normal glucose tolerance receiving Oral Glucose Tolerance Test
arm group label: Aim 2a: Teens with Cystic Fibrosis - High Glycemic Meal
arm group type: Active Comparator
description: Cystic Fibrosis subjects 12 years of age or older with normal glucose tolerance eating High Glycemic Index Meal
arm group label: Aim 2a: Teens with Cystic Fibrosis - Low Glycemic Meal
arm group type: Active Comparator
description: Cystic Fibrosis subjects 12 years of age or older with normal glucose tolerance eating Low Glycemic Index Meal
arm group label: Aim 2b: Cystic Fibrosis Consuming Test Soda
arm group type: Active Comparator
description: Participants with Cystic Fibrosis 12 years of age or older with normal glucose tolerance or impaired glucose tolerance consuming a test beverage of a test soda. A week later these participants will have an Oral Glucose Tolerance Test.
arm group label: Aim 2b: Cystic Fibrosis Consuming Fruit Juice
arm group type: Active Comparator
description: Participants with Cystic Fibrosis 12 years of age or older with normal glucose tolerance or impaired glucose tolerance consuming a test beverage of fruit juice. A week later these participants will have an Oral Glucose Tolerance Test.
intervention type: Other
intervention name: Oral Glucose Tolerance Test
description: 1.75 gm/kg to a maximum of 75 gm of an oral glucose solution
arm group label: Aim 1: Children with Cystic Fibrosis
arm group label: Aim 1: Control Children
arm group label: Aim 2b: Cystic Fibrosis Consuming Fruit Juice
arm group label: Aim 2b: Cystic Fibrosis Consuming Test Soda
other name: OGTT
intervention type: Other
intervention name: High Glycemic Index Meal
description: isocaloric breakfasts - set the high glycemic index to 80
The nutrient composition of each meal will be 10 kcal per kg, 50% kcal from carbohydrates, 20% kcal from protein, and 30% kcal from fat
arm group label: Aim 2a: Teens with Cystic Fibrosis - High Glycemic Meal
intervention type: Other
intervention name: Low Glycemic Index Meal
description: isocaloric breakfasts - set the low glycemic index to 30
The nutrient composition of each meal will be 10 kcal per kg, 50% kcal from carbohydrates, 20% kcal from protein, and 30% kcal from fat
arm group label: Aim 2a: Teens with Cystic Fibrosis - Low Glycemic Meal
intervention type: Other
intervention name: Test Soda
description: Test soda containing 60% fructose and 40% glucose at a dose of 1.75 grams per kilogram body weight to a maximum of 75 grams.
arm group label: Aim 2b: Cystic Fibrosis Consuming Test Soda
intervention type: Other
intervention name: Fruit juice
description: Fruit juice containing a combination fructose, glucose, and sucrose at a dose of 1.75 grams per kilogram body weight to a maximum of 75 grams
arm group label: Aim 2b: Cystic Fibrosis Consuming Fruit Juice
criteria: 
gender: All
minimum age: 1 Year
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Arlene Stecenko, MD
role: Principal Investigator
affiliation: Emory University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Arlene Stecenko
investigator title: Associate Professor
mesh term: Cystic Fibrosis
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Fibrosis
sharing ipd: No