<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/NCT03020719</url>
  </required_header>
  <id_info>
    <org_study_id>GROW-IP-16</org_study_id>
    <nct_id>NCT03020719</nct_id>
  </id_info>
  <brief_title>The Role of Oral Glutathione on Growth Parameters in Children With Cystic Fibrosis</brief_title>
  <acronym>GROW</acronym>
  <official_title>A Multi Center Placebo Controlled Double Blind Randomized Study Evaluating the Role of Oral Glutathione on Growth Parameters in Children With Cystic Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cystic Fibrosis Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this randomized, placebo-controlled (Phase II) study will be to further&#xD;
      evaluate the effects of oral glutathione on growth in children with CF.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      a prospective, multi-center, randomized, placebocontrolled, double-blind, Phase II clinical&#xD;
      trial. Approximately sixty pancreatic insufficient (PI) subjects with CF who are ≥ 2 and &lt; 11&#xD;
      years of age, will be enrolled to receive either L-Glutathione Reduced (GSH) or placebo given&#xD;
      orally (tid) for 24 weeks. Each subject will be seen for four study visits: Visit 1&#xD;
      (Screening), Visit 2 (Baseline/Randomization, Day 0), Visit 3 (Week 12) and Visit 4 (Week&#xD;
      24). At Visit 2, subjects will be randomized to receive either active treatment or placebo.&#xD;
      Visit 1 and 2 may be combined if subject meets eligibility requirements and a fecal specimen&#xD;
      is collected prior to dosing. Safety and clinical outcomes will be assessed throughout the&#xD;
      study. Assessment of inflammatory and other bio-markers in blood and fecal specimens will be&#xD;
      performed at Visits 2 and 4&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 14, 2017</start_date>
  <completion_date type="Actual">December 12, 2018</completion_date>
  <primary_completion_date type="Actual">December 12, 2018</primary_completion_date>
  <phase>Phase 2</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>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Weight-for-age Z-score</measure>
    <time_frame>Baseline to 24 weeks</time_frame>
    <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in weight-for-age Z-score. Weight-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Height-for-age Z-score</measure>
    <time_frame>Baseline to 24 weeks</time_frame>
    <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in height-for-age Z-score. Height-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in BMI-for-age Z-score</measure>
    <time_frame>Baseline to 24 weeks</time_frame>
    <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in BMI-for-age Z-score. BMI-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fecal Calprotectin</measure>
    <time_frame>Baseline to 24 weeks</time_frame>
    <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in fecal calprotectin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in High-sensitivity C-reactive Protein (Hs-CRP)</measure>
    <time_frame>Baseline to 24 weeks</time_frame>
    <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in hs-CRP.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Baseline to 24 weeks</time_frame>
    <description>The number and percentage of participants with at least one event over the 24 week follow-up period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Baseline to 24 weeks</time_frame>
    <description>Rate is defined as the number of events per participant follow-up month.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Oral Glutathione</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral Glutathione oral powder at 65mg/kg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo oral powder at 65mg/kg/day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral Glutathione</intervention_name>
    <description>Oral Glutathione oral powder</description>
    <arm_group_label>Oral Glutathione</arm_group_label>
    <other_name>GSH</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo oral powder</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Inactive powder</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female ≥ 2 and &lt; 11 years of age at Visit 1&#xD;
&#xD;
          2. Documentation of a CF diagnosis as evidenced by the following criteria: Sweat chloride&#xD;
             ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) AND Two&#xD;
             well-characterized mutations in the cystic fibrosis transmembrane conductive regulator&#xD;
             (CFTR) gene&#xD;
&#xD;
          3. Weight-for-age between the 10th and 50th percentiles at Screening (Visit 1) (using the&#xD;
             Center for Disease Control (CDC) reference equations)&#xD;
&#xD;
          4. Current chronic use, greater than 8 weeks before Day 0, of pancreatic enzyme&#xD;
             replacement therapy (PERT) for management of pancreatic insufficiency&#xD;
&#xD;
          5. Written informed consent (and assent when applicable) obtained from subject or&#xD;
             subject's legal representative and ability to comply with the requirements of the&#xD;
             study&#xD;
&#xD;
          6. Clinically stable with no significant changes in health status within 2 weeks prior to&#xD;
             Day 0&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Intestinal obstruction or gastrointestinal surgery within the 6 months prior to Day&#xD;
             0 2. History of diabetes, Crohn's disease, celiac disease, or bowel resection 3. Use&#xD;
             of either oral or inhaled GSH or N-acetyl cysteine within the 4 months prior to&#xD;
             Screening (Visit 1) 4. Known hypersensitivity to oral glutathione or lactose 5.&#xD;
             Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline,&#xD;
             azithromycin, Pulmozyme, Cayston TOBI Kalydeco,Orkambi, Proton Pump Inhibitor,&#xD;
             Histamine H-2 Blocker [PPI/H2-blocker], Miralax® , PERT, dietary supplementation,&#xD;
             probiotics) within the 4 weeks prior to Day 0 6. Changes in the amount of proprietary&#xD;
             dietary supplement formulas (e.g., Scandishakes, Boost, Pediasure, or homemade&#xD;
             formula) given (oral or gastrostomy tube) within the 4 weeks prior to Day 0 7. Use of&#xD;
             antibiotics (oral, IV, or inhaled) for acute symptoms within the 2 weeks prior to Day&#xD;
             0 8. Use of oral steroids within the 4 weeks prior to Day 0 9. Active treatment for&#xD;
             nontuberculous mycobacteria (NTM) at Day 0 10. Active treatment for allergic&#xD;
             bronchopulmonary aspergillosis (ABPA) at Day 0 11. Administration of any&#xD;
             investigational drug within the 30 days prior to Day 0 12. Sibling who received study&#xD;
             drug as part of this study 13. Presence of a condition or abnormality that in the&#xD;
             opinion of the investigator would compromise the safety of the patient or the quality&#xD;
             of the data&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>11 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sarah J Schwarzenberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Molly Bozic, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University School of Medicine Riley Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Childrens Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Connecticut Childrens Medical Center</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemours Childrens Clinic</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemours Children's Clinic</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riley Children's Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Childrens Hospital of Michigan</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helen DeVos Women and Childrens Center</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota Medical Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55414</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Childrens Mercy Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women and Childrens Hospital of Buffalo</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14222</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Childrens Hospital of New York/Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Vermont Inc.</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia Health System</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Childrens Hospital of Milwaukee</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>January 11, 2017</study_first_submitted>
  <study_first_submitted_qc>January 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <results_first_submitted>November 12, 2019</results_first_submitted>
  <results_first_submitted_qc>December 20, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">January 9, 2020</results_first_posted>
  <last_update_submitted>December 20, 2019</last_update_submitted>
  <last_update_submitted_qc>December 20, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Growth Parameters</keyword>
  <keyword>Cystic Fibrosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 22, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/19/NCT03020719/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 12, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/19/NCT03020719/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Oral Glutathione</title>
          <description>Oral Glutathione oral powder at 65mg/kg/day&#xD;
Oral Glutathione: Oral Glutathione oral powder</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo oral powder at 65mg/kg/day&#xD;
Placebo: Placebo oral powder</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Oral Glutathione</title>
          <description>Oral Glutathione oral powder at 65mg/kg/day&#xD;
Oral Glutathione: Oral Glutathione oral powder</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo oral powder at 65mg/kg/day&#xD;
Placebo: Placebo oral powder</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.1" spread="2.43"/>
                    <measurement group_id="B2" value="6" spread="2.87"/>
                    <measurement group_id="B3" value="6.1" spread="2.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Age Distribution</title>
              <category_list>
                <category>
                  <title>&lt; 6 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥ 6 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="59"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cystic Fibrosis (CF) Genotype</title>
          <description>Other refers to participants with either two known, non-F508 del CF mutations, or one known, non-F508 del CF mutation and one unidentified allele which has not been classified as a CF mutation. Unidentified refers to participants with 2 alleles that have not been classified as CF mutations.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Delta F508 Homozygous</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Delta F508 Heterozygous</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unidentified</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Available</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight (Z-score)</title>
          <description>Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <units>z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-0.57" spread="0.33"/>
                    <measurement group_id="B2" value="-0.53" spread="0.35"/>
                    <measurement group_id="B3" value="-0.55" spread="0.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight-for-age Z-score Distribution</title>
          <description>Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt; -0.52 (equiv. to &lt; 30th percentile)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥ -0.52 (equiv. to ≥ 30th percentile)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fecal Elastase</title>
          <description>Either historical fecal elastase or collected as part of the study.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt; 200 mg/g</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>≥ 200 mg/g</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Available</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Weight-for-age Z-score</title>
        <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in weight-for-age Z-score. Weight-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline to 24 weeks</time_frame>
        <population>Include participants with weight-for-age Z-score measurements at Baseline, Week 12 and Week 24</population>
        <group_list>
          <group group_id="O1">
            <title>Oral Glutathione</title>
            <description>Oral Glutathione oral powder at 65mg/kg/day&#xD;
Oral Glutathione: Oral Glutathione oral powder</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral powder at 65mg/kg/day&#xD;
Placebo: Placebo oral powder</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Weight-for-age Z-score</title>
          <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in weight-for-age Z-score. Weight-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <population>Include participants with weight-for-age Z-score measurements at Baseline, Week 12 and Week 24</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.018" lower_limit="-0.124" upper_limit="0.087"/>
                    <measurement group_id="O2" value="0.045" lower_limit="-0.073" upper_limit="0.163"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2521</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Model adjusted for randomization strata: sex, baseline age (&lt; 6 years, ≥ 6 years), and baseline weight-for-age z-score category (&lt; -0.52, ≥ -0.52).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.081</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.221</ci_lower_limit>
            <ci_upper_limit>0.059</ci_upper_limit>
            <estimate_desc>Model incorporates Week 12 weight-for-age z-score, assumes unstructured covariance for within-subject measurements, and includes a subject-level random intercept.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Height-for-age Z-score</title>
        <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in height-for-age Z-score. Height-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline to 24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral Glutathione</title>
            <description>Oral Glutathione oral powder at 65mg/kg/day&#xD;
Oral Glutathione: Oral Glutathione oral powder</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral powder at 65mg/kg/day&#xD;
Placebo: Placebo oral powder</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Height-for-age Z-score</title>
          <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in height-for-age Z-score. Height-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" spread="0.21"/>
                    <measurement group_id="O2" value="0.03" spread="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0890</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Model adjusted for randomization strata: sex, baseline age (&lt;6 years, ≥6 years), and baseline weight-for-age z-score category (&lt; -0.52, ≥-0.52).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.08</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.18</ci_lower_limit>
            <ci_upper_limit>0.01</ci_upper_limit>
            <estimate_desc>Model incorporates Week 12 measurements, assumes unstructured covariance for within-subject measurements, and includes a subject-level random intercept.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in BMI-for-age Z-score</title>
        <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in BMI-for-age Z-score. BMI-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
        <time_frame>Baseline to 24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral Glutathione</title>
            <description>Oral Glutathione oral powder at 65mg/kg/day&#xD;
Oral Glutathione: Oral Glutathione oral powder</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral powder at 65mg/kg/day&#xD;
Placebo: Placebo oral powder</description>
          </group>
        </group_list>
        <measure>
          <title>Change in BMI-for-age Z-score</title>
          <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in BMI-for-age Z-score. BMI-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.</description>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.01" spread="0.48"/>
                    <measurement group_id="O2" value="0.04" spread="0.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5730</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Model adjusted from randomization strata: sex, baseline age (&lt;6 years, ≥6 years), and baseline weight-for-age z-score category (&lt; -0.52, ≥-0.52).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.06</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.28</ci_lower_limit>
            <ci_upper_limit>0.15</ci_upper_limit>
            <estimate_desc>Model incorporates Week 12 measurements, assumes unstructured covariance for within-subject measurements, and includes a subject-level random intercept.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Fecal Calprotectin</title>
        <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in fecal calprotectin.</description>
        <time_frame>Baseline to 24 weeks</time_frame>
        <population>Include participants with fecal calprotectin measurements at Baseline and Week 24.</population>
        <group_list>
          <group group_id="O1">
            <title>Oral Glutathione</title>
            <description>Oral Glutathione oral powder at 65mg/kg/day&#xD;
Oral Glutathione: Oral Glutathione oral powder</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral powder at 65mg/kg/day&#xD;
Placebo: Placebo oral powder</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Fecal Calprotectin</title>
          <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in fecal calprotectin.</description>
          <population>Include participants with fecal calprotectin measurements at Baseline and Week 24.</population>
          <units>log base 10 transformation of ug/g</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.05" spread="0.55"/>
                    <measurement group_id="O2" value="-0.05" spread="0.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4259</p_value>
            <method>Mixed Models Analysis</method>
            <method_desc>Model adjusted for randomization strata: sex, baseline age (&lt;6 years, ≥6 years), and baseline weight-for-age z-score category (&lt; -0.52, ≥-0.52).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.11</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.17</ci_lower_limit>
            <ci_upper_limit>0.40</ci_upper_limit>
            <estimate_desc>Model incorporates Week 12 measurements, assumes unstructured covariance for within-subject measurements, and includes a subject-level random intercept.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in High-sensitivity C-reactive Protein (Hs-CRP)</title>
        <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in hs-CRP.</description>
        <time_frame>Baseline to 24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral Glutathione</title>
            <description>Oral Glutathione oral powder at 65mg/kg/day&#xD;
Oral Glutathione: Oral Glutathione oral powder</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral powder at 65mg/kg/day&#xD;
Placebo: Placebo oral powder</description>
          </group>
        </group_list>
        <measure>
          <title>Change in High-sensitivity C-reactive Protein (Hs-CRP)</title>
          <description>Difference between the oral glutathione and placebo groups in the 24-week change from baseline in hs-CRP.</description>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.45" spread="3.4"/>
                    <measurement group_id="O2" value="-0.04" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4666</p_value>
            <method>ANCOVA</method>
            <method_desc>Model adjusted for randomization strata: sex, baseline age (&lt;6 years, ≥6 years), and baseline weight-for-age z-score category (&lt; -0.52, ≥-0.52).</method_desc>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.55</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.06</ci_lower_limit>
            <ci_upper_limit>0.96</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
        <description>The number and percentage of participants with at least one event over the 24 week follow-up period.</description>
        <time_frame>Baseline to 24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral Glutathione</title>
            <description>Oral Glutathione oral powder at 65mg/kg/day&#xD;
Oral Glutathione: Oral Glutathione oral powder</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral powder at 65mg/kg/day&#xD;
Placebo: Placebo oral powder</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
          <description>The number and percentage of participants with at least one event over the 24 week follow-up period.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.0000</p_value>
            <method>Fisher Exact</method>
            <param_type>Difference in % of Participants with AE</param_type>
            <param_value>0.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-13.6</ci_lower_limit>
            <ci_upper_limit>13.6</ci_upper_limit>
            <estimate_desc>95% CI calculated using the Newcombe-Wilson method without continuity correction.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1945</p_value>
            <method>Fisher Exact</method>
            <param_type>Difference in % of Participants with SAE</param_type>
            <param_value>-13.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-30.5</ci_lower_limit>
            <ci_upper_limit>2.9</ci_upper_limit>
            <estimate_desc>95% CI calculated using the Newcombe-Wilson method without continuity correction.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
        <description>Rate is defined as the number of events per participant follow-up month.</description>
        <time_frame>Baseline to 24 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral Glutathione</title>
            <description>Oral Glutathione oral powder at 65mg/kg/day&#xD;
Oral Glutathione: Oral Glutathione oral powder</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo oral powder at 65mg/kg/day&#xD;
Placebo: Placebo oral powder</description>
          </group>
        </group_list>
        <measure>
          <title>Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)</title>
          <description>Rate is defined as the number of events per participant follow-up month.</description>
          <units>number of events/total follow-up months</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.89"/>
                    <measurement group_id="O2" value="0.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious Adverse Events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01"/>
                    <measurement group_id="O2" value="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Rate Ratio for Adverse Events calculated using Poisson Regression with an offset for the log of follow-up time in months. The total number of follow-up months of all participants (not per participant) in the trial was as follows: in the GSH group was 179.22 and in the Placebo group was 177.19.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1087</p_value>
            <method>Poisson Regression</method>
            <param_type>Rate Ratio</param_type>
            <param_value>1.21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.96</ci_lower_limit>
            <ci_upper_limit>1.52</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Rate Ratio for Serious Adverse Events calculated using Poisson Regression with an offset for the log of follow-up time in months. The total number of follow-up months of all participants (not per participant) in the trial was as follows: in the GSH group was 179.22 and in the Placebo group was 177.19.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0122</p_value>
            <method>Poisson Regression</method>
            <param_type>Rate Ratio</param_type>
            <param_value>0.12</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.01</ci_lower_limit>
            <ci_upper_limit>0.67</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Oral Glutathione</title>
          <description>Oral Glutathione oral powder at 65mg/kg/day&#xD;
Oral Glutathione: Oral Glutathione oral powder</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo oral powder at 65mg/kg/day&#xD;
Placebo: Placebo oral powder</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (20.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Distal intestinal obstruction syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Infective pulmonary exacerbation of cystic fibrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (20.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Steatorrhoea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="30"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="8" subjects_at_risk="30"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Otitis media</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pulmonary function test decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Clubbing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="24" subjects_affected="13" subjects_at_risk="30"/>
                <counts group_id="E2" events="14" subjects_affected="12" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Infective pulmonary exacerbation of cystic fibrosis</sub_title>
                <counts group_id="E1" events="14" subjects_affected="10" subjects_at_risk="30"/>
                <counts group_id="E2" events="11" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sinus congestion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Arthur Baines</name_or_title>
      <organization>Seattle Children's Hospital</organization>
      <phone>2068841431</phone>
      <email>Arthur.Baines@seattlechildrens.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03020719
org study id: GROW-IP-16
nct id: NCT03020719
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this randomized, placebo-controlled (Phase II) study will be to further
      evaluate the effects of oral glutathione on growth in children with CF.
a prospective, multi-center, randomized, placebocontrolled, double-blind, Phase II clinical
      trial. Approximately sixty pancreatic insufficient (PI) subjects with CF who are ≥ 2 and < 11
      years of age, will be enrolled to receive either L-Glutathione Reduced (GSH) or placebo given
      orally (tid) for 24 weeks. Each subject will be seen for four study visits: Visit 1
      (Screening), Visit 2 (Baseline/Randomization, Day 0), Visit 3 (Week 12) and Visit 4 (Week
      24). At Visit 2, subjects will be randomized to receive either active treatment or placebo.
      Visit 1 and 2 may be combined if subject meets eligibility requirements and a fecal specimen
      is collected prior to dosing. Safety and clinical outcomes will be assessed throughout the
      study. Assessment of inflammatory and other bio-markers in blood and fecal specimens will be
      performed at Visits 2 and 4
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in Weight-for-age Z-score
time frame: Baseline to 24 weeks
description: Difference between the oral glutathione and placebo groups in the 24-week change from baseline in weight-for-age Z-score. Weight-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change in Height-for-age Z-score
time frame: Baseline to 24 weeks
description: Difference between the oral glutathione and placebo groups in the 24-week change from baseline in height-for-age Z-score. Height-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change in BMI-for-age Z-score
time frame: Baseline to 24 weeks
description: Difference between the oral glutathione and placebo groups in the 24-week change from baseline in BMI-for-age Z-score. BMI-for-age Z-scores are derived from the 2000 Centers for Disease Control and Prevention growth charts for U.S. children. The reference population in these growth charts is children surveyed by the National Center for Health Statistics from 1963-65 to 1988-94. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the mean while a positive Z-score indicates values higher than the mean.
measure: Change in Fecal Calprotectin
time frame: Baseline to 24 weeks
description: Difference between the oral glutathione and placebo groups in the 24-week change from baseline in fecal calprotectin.
measure: Change in High-sensitivity C-reactive Protein (Hs-CRP)
time frame: Baseline to 24 weeks
description: Difference between the oral glutathione and placebo groups in the 24-week change from baseline in hs-CRP.
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Baseline to 24 weeks
description: The number and percentage of participants with at least one event over the 24 week follow-up period.
measure: Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Baseline to 24 weeks
description: Rate is defined as the number of events per participant follow-up month.
arm group label: Oral Glutathione
arm group type: Experimental
description: Oral Glutathione oral powder at 65mg/kg/day
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo oral powder at 65mg/kg/day
intervention type: Drug
intervention name: Oral Glutathione
description: Oral Glutathione oral powder
arm group label: Oral Glutathione
other name: GSH
intervention type: Drug
intervention name: Placebo
description: Placebo oral powder
arm group label: Placebo
other name: Inactive powder
criteria: 
gender: All
minimum age: 2 Years
maximum age: 11 Years
healthy volunteers: No
last name: Sarah J Schwarzenberg, MD
role: Principal Investigator
affiliation: University of Minnesota
last name: Molly Bozic, MD
role: Principal Investigator
affiliation: Indiana University School of Medicine Riley Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 