<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/NCT03771560</url>
  </required_header>
  <id_info>
    <org_study_id>Folinic acid</org_study_id>
    <nct_id>NCT03771560</nct_id>
  </id_info>
  <brief_title>Folinic Acid in Autism</brief_title>
  <official_title>An Examination of Changes in Urinary Metabolites With Use of Folinic Acid in Children With Autism Spectrum Disorder (ASD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>No</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>
      An examination of changes in urinary metabolites with use of folinic acid in children with&#xD;
      autism spectrum disorder (ASD). Investigators will also measure behavioral measures and&#xD;
      academic measures monthly at school with teachers and parents report.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Children enrolled in Oak Hill School will enroll in this study and take folinic acid&#xD;
      supplement twice a day for 12 weeks period. Behavioral measures and urinary metabolites will&#xD;
      be collected pre and post treatment. Behavioral measures will be taken again at 16 weeks,&#xD;
      after 4 weeks of not dosing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 15, 2018</start_date>
  <completion_date type="Actual">June 30, 2018</completion_date>
  <primary_completion_date type="Actual">June 30, 2018</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Aberrant Behavior Checklist (ABC) - Parent Reported Change</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>The Aberrant Behavior Checklist - parent reported version measures aberrant behavior in children and young adults. There are 58 questions.The scoring of one question can range from 0 (not a problem) to 3 (severe) points on a Likert scale. The total possible score range for the ABC is 0 - 174. Analysis will be performed for mean of total score change over time.&#xD;
Scoring from 0-3&#xD;
Not a problem = 0, Slightly = 1, Moderately Serious =2, Severe =3&#xD;
Lower score indicates better performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Aberrant Behavior Checklist (ABC) - Teacher Reported Change</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>The Aberrant Behavior Checklist - teacher reported version measures aberrant behavior in children and young adults. There are 58 questions. The scoring of ABC questions can range from 0 (not a problem) to 3 (severe) points on a likert scale. The total possible score range for the ABC is 0 - 174. Analysis will be performed for mean of total score change over time.&#xD;
Scoring from 0-3&#xD;
Not a problem = 0, Slightly = 1, Moderately Serious =2, Severe =3&#xD;
Lower score indicates better performance.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Social Responsiveness Scale (SRS) - Parent Reported Change</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>The Social Responsiveness Scale - parent reported version measures social ability in children and young adults. There are 65 questions. The questions on the scale with anchors 1 (Not True) - 4 (Almost Always True). The scoring of SRS questions can range from 0-3 (with possible reverse scoring) based on scoring instructions for data analysis. The total possible score range for the SRS is 0 - 195. Analysis will be performed for mean of total score change over time.&#xD;
Anchors Not True = 1 Sometimes True = 2 Often True = 3 Almost Always True = 4&#xD;
Lower score indicates better performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Social Responsiveness Scale (SRS) - Teacher Reported Change</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>The Social Responsiveness Scale - teacher reported version measures social ability in children and young adults. There are 65 questions. The questions on the scale with anchors 1 (Not True) - 4 (Almost Always True). The scoring of SRS questions can range from 0-3 (with possible reverse scoring) based on scoring instructions for data analysis. The total possible score range for the SRS is 0 - 195. Analysis will be performed for mean of total score change over time.&#xD;
Anchors Not True = 1 Sometimes True = 2 Often True = 3 Almost Always True = 4&#xD;
Lower score indicates better performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pediatric Quality of Life (PedsQL) - Parent Reported Change</measure>
    <time_frame>Baseline to Week 12</time_frame>
    <description>Pediatric Quality of Life is reported by parent only and it assesses improvement of the child's overall quality of life through questions about physical, emotional, social and school functioning. There are 23 questions. The scoring of PedsQL questions can range from 0 (Never) to 4 (Almost Always) points on a Likert scale. Questions are reversed scored and linearly transformed to a 0 - 100 scale for data analysis as follows: 0=100, 1=75, 2=50, 3=23, 4=0. The total score = sum of all the questions over the number of items answered on. The total possible score range for the PedsQL is 0 - 100. Analysis will be performed for mean of total score change over time.&#xD;
Scoring from 0 to 4&#xD;
Never = 0, Almost Never = 1, Sometimes = 2, Often = 3, Almost Always =4&#xD;
Higher score indicates better performance.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Autism Spectrum Disorder</condition>
  <arm_group>
    <arm_group_label>Open-label</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this open-label trial, all subjects will receive the twice daily dose of folinic acid. Folinic acid will be delivered in pill form at a weight-based dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>folinic acid</intervention_name>
    <description>subject will take folinic acid daily for 12 weeks</description>
    <arm_group_label>Open-label</arm_group_label>
    <other_name>leucovorin calcium</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Between ages 5 and 25&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not currently taking folinic acid&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert Hendren, DO</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>February 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 8, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <results_first_submitted>September 5, 2019</results_first_submitted>
  <results_first_submitted_qc>November 12, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">December 3, 2019</results_first_posted>
  <last_update_submitted>November 12, 2019</last_update_submitted>
  <last_update_submitted_qc>November 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Robert Hendren</investigator_full_name>
    <investigator_title>Professor of Psychiatry</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leucovorin</mesh_term>
    <mesh_term>Folic Acid</mesh_term>
    <mesh_term>Levoleucovorin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 21, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03771560/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Folinic Acid Open-label</title>
          <description>In this open-label trial, all subjects will receive the twice daily dose of folinic acid. Folinic acid will be delivered in pill form at a weight-based dose.&#xD;
folinic acid: subject will take folinic acid daily for 12 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Children with ASD enrolled in Oak Hill school and completed the entire study.</population>
      <group_list>
        <group group_id="B1">
          <title>Folinic Acid Open-label</title>
          <description>In this open-label trial, all subjects will receive the twice daily dose of folinic acid. Folinic acid will be delivered in pill form at a weight-based dose.&#xD;
folinic acid: subject will take folinic acid daily for 12 weeks</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16" lower_limit="13" upper_limit="18"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Aberrant Behavior Checklist (ABC) - Parent Reported Change</title>
        <description>The Aberrant Behavior Checklist - parent reported version measures aberrant behavior in children and young adults. There are 58 questions.The scoring of one question can range from 0 (not a problem) to 3 (severe) points on a Likert scale. The total possible score range for the ABC is 0 - 174. Analysis will be performed for mean of total score change over time.&#xD;
Scoring from 0-3&#xD;
Not a problem = 0, Slightly = 1, Moderately Serious =2, Severe =3&#xD;
Lower score indicates better performance.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Folinic Acid Open-label</title>
            <description>In this open-label trial, all subjects will receive the twice daily dose of folinic acid. Folinic acid will be delivered in pill form at a weight-based dose.&#xD;
folinic acid: subject will take folinic acid daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Aberrant Behavior Checklist (ABC) - Parent Reported Change</title>
          <description>The Aberrant Behavior Checklist - parent reported version measures aberrant behavior in children and young adults. There are 58 questions.The scoring of one question can range from 0 (not a problem) to 3 (severe) points on a Likert scale. The total possible score range for the ABC is 0 - 174. Analysis will be performed for mean of total score change over time.&#xD;
Scoring from 0-3&#xD;
Not a problem = 0, Slightly = 1, Moderately Serious =2, Severe =3&#xD;
Lower score indicates better performance.</description>
          <units>score on a scale</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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" lower_limit="-11.3" upper_limit="6.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The parent-reported change in mean ABC total score from baseline to week 12.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.56</p_value>
            <method>Paired Sample t-test</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-2.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-11.3</ci_lower_limit>
            <ci_upper_limit>6.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Aberrant Behavior Checklist (ABC) - Teacher Reported Change</title>
        <description>The Aberrant Behavior Checklist - teacher reported version measures aberrant behavior in children and young adults. There are 58 questions. The scoring of ABC questions can range from 0 (not a problem) to 3 (severe) points on a likert scale. The total possible score range for the ABC is 0 - 174. Analysis will be performed for mean of total score change over time.&#xD;
Scoring from 0-3&#xD;
Not a problem = 0, Slightly = 1, Moderately Serious =2, Severe =3&#xD;
Lower score indicates better performance.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>Deleted one outlier for data analysis; deleted one subject because of missing survey time point from teacher.</population>
        <group_list>
          <group group_id="O1">
            <title>Folinic Acid Open-label</title>
            <description>In this open-label trial, all subjects will receive the twice daily dose of folinic acid. Folinic acid will be delivered in pill form at a weight-based dose.&#xD;
folinic acid: subject will take folinic acid daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Aberrant Behavior Checklist (ABC) - Teacher Reported Change</title>
          <description>The Aberrant Behavior Checklist - teacher reported version measures aberrant behavior in children and young adults. There are 58 questions. The scoring of ABC questions can range from 0 (not a problem) to 3 (severe) points on a likert scale. The total possible score range for the ABC is 0 - 174. Analysis will be performed for mean of total score change over time.&#xD;
Scoring from 0-3&#xD;
Not a problem = 0, Slightly = 1, Moderately Serious =2, Severe =3&#xD;
Lower score indicates better performance.</description>
          <population>Deleted one outlier for data analysis; deleted one subject because of missing survey time point from teacher.</population>
          <units>score on a scale</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="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" lower_limit="-5.2" upper_limit="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The teacher-reported change in mean ABC total score from baseline to week 12.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.68</p_value>
            <method>Paired Sample t-test</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>1.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.2</ci_lower_limit>
            <ci_upper_limit>7.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Social Responsiveness Scale (SRS) - Parent Reported Change</title>
        <description>The Social Responsiveness Scale - parent reported version measures social ability in children and young adults. There are 65 questions. The questions on the scale with anchors 1 (Not True) - 4 (Almost Always True). The scoring of SRS questions can range from 0-3 (with possible reverse scoring) based on scoring instructions for data analysis. The total possible score range for the SRS is 0 - 195. Analysis will be performed for mean of total score change over time.&#xD;
Anchors Not True = 1 Sometimes True = 2 Often True = 3 Almost Always True = 4&#xD;
Lower score indicates better performance.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Folinic Acid Open-label</title>
            <description>In this open-label trial, all subjects will receive the twice daily dose of folinic acid. Folinic acid will be delivered in pill form at a weight-based dose.&#xD;
folinic acid: subject will take folinic acid daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Social Responsiveness Scale (SRS) - Parent Reported Change</title>
          <description>The Social Responsiveness Scale - parent reported version measures social ability in children and young adults. There are 65 questions. The questions on the scale with anchors 1 (Not True) - 4 (Almost Always True). The scoring of SRS questions can range from 0-3 (with possible reverse scoring) based on scoring instructions for data analysis. The total possible score range for the SRS is 0 - 195. Analysis will be performed for mean of total score change over time.&#xD;
Anchors Not True = 1 Sometimes True = 2 Often True = 3 Almost Always True = 4&#xD;
Lower score indicates better performance.</description>
          <units>score on a scale</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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.8" lower_limit="-17.3" upper_limit="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The parent-reported change in mean SRS total score from baseline to week 12.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.095</p_value>
            <method>Paired Sample t-test</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-7.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-17.3</ci_lower_limit>
            <ci_upper_limit>1.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Social Responsiveness Scale (SRS) - Teacher Reported Change</title>
        <description>The Social Responsiveness Scale - teacher reported version measures social ability in children and young adults. There are 65 questions. The questions on the scale with anchors 1 (Not True) - 4 (Almost Always True). The scoring of SRS questions can range from 0-3 (with possible reverse scoring) based on scoring instructions for data analysis. The total possible score range for the SRS is 0 - 195. Analysis will be performed for mean of total score change over time.&#xD;
Anchors Not True = 1 Sometimes True = 2 Often True = 3 Almost Always True = 4&#xD;
Lower score indicates better performance.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <population>Deleted one outlier for data analysis; deleted one subject because of missing survey time point from teacher.</population>
        <group_list>
          <group group_id="O1">
            <title>Folinic Acid Open-label</title>
            <description>In this open-label trial, all subjects will receive the twice daily dose of folinic acid. Folinic acid will be delivered in pill form at a weight-based dose.&#xD;
folinic acid: subject will take folinic acid daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Social Responsiveness Scale (SRS) - Teacher Reported Change</title>
          <description>The Social Responsiveness Scale - teacher reported version measures social ability in children and young adults. There are 65 questions. The questions on the scale with anchors 1 (Not True) - 4 (Almost Always True). The scoring of SRS questions can range from 0-3 (with possible reverse scoring) based on scoring instructions for data analysis. The total possible score range for the SRS is 0 - 195. Analysis will be performed for mean of total score change over time.&#xD;
Anchors Not True = 1 Sometimes True = 2 Often True = 3 Almost Always True = 4&#xD;
Lower score indicates better performance.</description>
          <population>Deleted one outlier for data analysis; deleted one subject because of missing survey time point from teacher.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" lower_limit="-7.0" upper_limit="13.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The teacher-reported change in mean SRS total score from baseline to week 12.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.95</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>-0.5</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.0</ci_lower_limit>
            <ci_upper_limit>13.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pediatric Quality of Life (PedsQL) - Parent Reported Change</title>
        <description>Pediatric Quality of Life is reported by parent only and it assesses improvement of the child's overall quality of life through questions about physical, emotional, social and school functioning. There are 23 questions. The scoring of PedsQL questions can range from 0 (Never) to 4 (Almost Always) points on a Likert scale. Questions are reversed scored and linearly transformed to a 0 - 100 scale for data analysis as follows: 0=100, 1=75, 2=50, 3=23, 4=0. The total score = sum of all the questions over the number of items answered on. The total possible score range for the PedsQL is 0 - 100. Analysis will be performed for mean of total score change over time.&#xD;
Scoring from 0 to 4&#xD;
Never = 0, Almost Never = 1, Sometimes = 2, Often = 3, Almost Always =4&#xD;
Higher score indicates better performance.</description>
        <time_frame>Baseline to Week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Folinic Acid Open-label</title>
            <description>In this open-label trial, all subjects will receive the twice daily dose of folinic acid. Folinic acid will be delivered in pill form at a weight-based dose.&#xD;
folinic acid: subject will take folinic acid daily for 12 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Pediatric Quality of Life (PedsQL) - Parent Reported Change</title>
          <description>Pediatric Quality of Life is reported by parent only and it assesses improvement of the child's overall quality of life through questions about physical, emotional, social and school functioning. There are 23 questions. The scoring of PedsQL questions can range from 0 (Never) to 4 (Almost Always) points on a Likert scale. Questions are reversed scored and linearly transformed to a 0 - 100 scale for data analysis as follows: 0=100, 1=75, 2=50, 3=23, 4=0. The total score = sum of all the questions over the number of items answered on. The total possible score range for the PedsQL is 0 - 100. Analysis will be performed for mean of total score change over time.&#xD;
Scoring from 0 to 4&#xD;
Never = 0, Almost Never = 1, Sometimes = 2, Often = 3, Almost Always =4&#xD;
Higher score indicates better performance.</description>
          <units>score on a scale</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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" lower_limit="-5.2" upper_limit="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>The parent-reported change in mean PedsQL total score from baseline to week 12.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.69</p_value>
            <method>Paired Sample t-test</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.8</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.2</ci_lower_limit>
            <ci_upper_limit>3.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Folinic Acid Open-label</title>
          <description>In this open-label trial, all subjects will receive the twice daily dose of folinic acid. Folinic acid will be delivered in pill form at a weight-based dose.&#xD;
folinic acid: subject will take folinic acid daily for 12 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <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="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="5" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upset Stomach</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Blood in Stool</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Increased aggression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cold</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </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>Dr. Robert Hendren</name_or_title>
      <organization>UCSF</organization>
      <phone>415-502-3500</phone>
      <email>STAR@ucsf.edu</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/NCT03771560
org study id: Folinic acid
nct id: NCT03771560
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
An examination of changes in urinary metabolites with use of folinic acid in children with
      autism spectrum disorder (ASD). Investigators will also measure behavioral measures and
      academic measures monthly at school with teachers and parents report.
Children enrolled in Oak Hill School will enroll in this study and take folinic acid
      supplement twice a day for 12 weeks period. Behavioral measures and urinary metabolites will
      be collected pre and post treatment. Behavioral measures will be taken again at 16 weeks,
      after 4 weeks of not dosing.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Aberrant Behavior Checklist (ABC) - Parent Reported Change
time frame: Baseline to Week 12
description: The Aberrant Behavior Checklist - parent reported version measures aberrant behavior in children and young adults. There are 58 questions.The scoring of one question can range from 0 (not a problem) to 3 (severe) points on a Likert scale. The total possible score range for the ABC is 0 - 174. Analysis will be performed for mean of total score change over time.
Scoring from 0-3
Not a problem = 0, Slightly = 1, Moderately Serious =2, Severe =3
Lower score indicates better performance.
measure: Aberrant Behavior Checklist (ABC) - Teacher Reported Change
time frame: Baseline to Week 12
description: The Aberrant Behavior Checklist - teacher reported version measures aberrant behavior in children and young adults. There are 58 questions. The scoring of ABC questions can range from 0 (not a problem) to 3 (severe) points on a likert scale. The total possible score range for the ABC is 0 - 174. Analysis will be performed for mean of total score change over time.
Scoring from 0-3
Not a problem = 0, Slightly = 1, Moderately Serious =2, Severe =3
Lower score indicates better performance.
measure: Social Responsiveness Scale (SRS) - Parent Reported Change
time frame: Baseline to Week 12
description: The Social Responsiveness Scale - parent reported version measures social ability in children and young adults. There are 65 questions. The questions on the scale with anchors 1 (Not True) - 4 (Almost Always True). The scoring of SRS questions can range from 0-3 (with possible reverse scoring) based on scoring instructions for data analysis. The total possible score range for the SRS is 0 - 195. Analysis will be performed for mean of total score change over time.
Anchors Not True = 1 Sometimes True = 2 Often True = 3 Almost Always True = 4
Lower score indicates better performance.
measure: Social Responsiveness Scale (SRS) - Teacher Reported Change
time frame: Baseline to Week 12
description: The Social Responsiveness Scale - teacher reported version measures social ability in children and young adults. There are 65 questions. The questions on the scale with anchors 1 (Not True) - 4 (Almost Always True). The scoring of SRS questions can range from 0-3 (with possible reverse scoring) based on scoring instructions for data analysis. The total possible score range for the SRS is 0 - 195. Analysis will be performed for mean of total score change over time.
Anchors Not True = 1 Sometimes True = 2 Often True = 3 Almost Always True = 4
Lower score indicates better performance.
measure: Pediatric Quality of Life (PedsQL) - Parent Reported Change
time frame: Baseline to Week 12
description: Pediatric Quality of Life is reported by parent only and it assesses improvement of the child's overall quality of life through questions about physical, emotional, social and school functioning. There are 23 questions. The scoring of PedsQL questions can range from 0 (Never) to 4 (Almost Always) points on a Likert scale. Questions are reversed scored and linearly transformed to a 0 - 100 scale for data analysis as follows: 0=100, 1=75, 2=50, 3=23, 4=0. The total score = sum of all the questions over the number of items answered on. The total possible score range for the PedsQL is 0 - 100. Analysis will be performed for mean of total score change over time.
Scoring from 0 to 4
Never = 0, Almost Never = 1, Sometimes = 2, Often = 3, Almost Always =4
Higher score indicates better performance.
arm group label: Open-label
arm group type: Experimental
description: In this open-label trial, all subjects will receive the twice daily dose of folinic acid. Folinic acid will be delivered in pill form at a weight-based dose.
intervention type: Drug
intervention name: folinic acid
description: subject will take folinic acid daily for 12 weeks
arm group label: Open-label
other name: leucovorin calcium
criteria: 
gender: All
minimum age: 5 Years
maximum age: 25 Years
healthy volunteers: No
last name: Robert Hendren, DO
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Robert Hendren
investigator title: Professor of Psychiatry
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Leucovorin
mesh term: Folic Acid
mesh term: Levoleucovorin
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 