<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/NCT01683565</url>
  </required_header>
  <id_info>
    <org_study_id>752311</org_study_id>
    <nct_id>NCT01683565</nct_id>
  </id_info>
  <brief_title>Preemie Tots: A Pilot Study to Understand the Effects of Prematurity in Toddlerhood</brief_title>
  <official_title>Preemie Tots: A Pilot Study to Understand the Effects of Prematurity in Toddlerhood</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sarah Keim</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cures Within Reach</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Marci and Bill Ingram Fund for Autism Spectrum Disorders Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Nationwide Children's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to examine whether supplementation with certain polyunsaturated&#xD;
      fatty acids can help development and behavior of children born preterm.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2012</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Child Behavior - Pervasive Developmental Disorders Screening Test-II Stage 2</measure>
    <time_frame>Baseline to 90 days post randomization</time_frame>
    <description>The Pervasive Developmental Disorders Screening Test-II stage 2 (PDDST-II) is a 14-item measure designed to discriminate Autism Spectrum Disorders from a related non-autistic developmental disorder in children ages 12 to 48 months old. The min score is 0 and the max score is 14. Scores equal to or greater than five yield a positive screen for autism. PDDST-II scores were measured at baseline and then again at study completion (90 days post randomization). The scores were calculated as the PDDST-II value at 90 days minus the PDDST-II value at baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA)</measure>
    <time_frame>Baseline to 90 days post randomization</time_frame>
    <description>Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a 42 item tool that is useful for identifying social-emotional problems and/or deficits in children. BITSEA includes the following subscales: Competence (11 Items, min score:0, max score:22), problem behaviors--dysregulation (8 items, min score:0, max score:16) , externalizing (6 items, min score:0, max score:12), internalizing (8 items, min score:0, max score:16), Autism Spectrum Disorder (17 Items, min score:0, max score:34), and Red Flags (14 items, min score:0, max score:28).The questions overlap and the problem subscale is a combination of dysregulation, externalizing, and internalizing. Higher problem scores indicate greater levels of social-emotional/behavioral problems. Lower Competence scores indicate possible delay/deficit. Scores were measured at baseline and then again at study completion (90 days post randomization). The change in BITSEA scores were calculated as the value at 90 days - the value at baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fatty Acid</measure>
    <time_frame>Baseline to 90 days post randomization</time_frame>
    <description>The secondary outcome measures in this trial involve an examination of change in fatty acids from the first study visit to the final study visit.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Feasibility: Future Full-scale Multi-site Study</measure>
    <time_frame>Pre-baseline to 90 days post randomization</time_frame>
    <description>Feasibility of a future full-scale multi-site study is assessed by examining the number of children screened, the proportion of these children who screen positive for ASD, the number of children who agree to participate in the trial, the number of children who return for the second and third study visits, baseline differences in individual fatty acids between the intervention and comparison groups, and adherence to the assigned treatment.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Preterm Birth</condition>
  <condition>Child Development</condition>
  <condition>Child Behavior</condition>
  <arm_group>
    <arm_group_label>LCPUFA Oil Supplement</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EPA + DHA + GLA + OA oil supplement</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Canola Oil Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LCPUFA oil supplement</intervention_name>
    <description>2.5mL per day for 90 days&#xD;
Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)</description>
    <arm_group_label>LCPUFA Oil Supplement</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Canola Oil Placebo</intervention_name>
    <description>2.5mL per day for 90 days</description>
    <arm_group_label>Canola Oil Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Child born at less than or equal to 29 completed weeks' gestation;&#xD;
&#xD;
          2. Child between 18 months, 0 days and 38 months, 30 days old chronological age;&#xD;
&#xD;
          3. Child admitted to NICU and/or had a Neonatology Clinic follow up visit scheduled.&#xD;
&#xD;
          4. Child showing some autistic symptoms;&#xD;
&#xD;
          5. Child between the 5th and 95th percentiles (per WHO growth chart) for weight at&#xD;
             his/her most recent hospital visit;&#xD;
&#xD;
          6. English spoken in the home, demonstrate ability to communicate in English well-enough&#xD;
             to understand study, informed consent, and study questionnaires; and&#xD;
&#xD;
          7. Have informed consent on file.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Consume LCPUFA supplement drops, chews, powders, Pediasure, or fatty fish more than 2x&#xD;
             per week;&#xD;
&#xD;
          2. Unable to tolerate venipuncture;&#xD;
&#xD;
          3. Any major malformation that would preclude participation;&#xD;
&#xD;
          4. Cerebral Palsy (quadriparesis only);&#xD;
&#xD;
          5. Deafness;&#xD;
&#xD;
          6. Blindness;&#xD;
&#xD;
          7. Bleeding disorder;&#xD;
&#xD;
          8. Type I diabetes;&#xD;
&#xD;
          9. Fragile X Syndrome, Rett Syndrome, Angelman Syndrome, Tuberous Sclerosis;&#xD;
&#xD;
         10. Non febrile seizure in the last month without a clear and resolved etiology;&#xD;
&#xD;
         11. Feeding problem that may inhibit full participation;&#xD;
&#xD;
         12. Known fish allergy;&#xD;
&#xD;
         13. Known canola/rapeseed allergy or sensitivity; or&#xD;
&#xD;
         14. Recorded score of &lt;70 on Bayley Cognitive Section within the past year.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Months</minimum_age>
    <maximum_age>39 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sarah Keim, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nationwide Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2012</study_first_posted>
  <results_first_submitted>July 25, 2018</results_first_submitted>
  <results_first_submitted_qc>December 11, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">January 3, 2019</results_first_posted>
  <last_update_submitted>December 11, 2018</last_update_submitted>
  <last_update_submitted_qc>December 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Nationwide Children's Hospital</investigator_affiliation>
    <investigator_full_name>Sarah Keim</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Premature Birth</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement</title>
          <description>Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA)&#xD;
+ Gamma-Linolenic acid (GLA) + Oleic Acid (OA)&#xD;
LCPUFA oil supplement: 2.5mL per day for 90 days&#xD;
Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg</description>
        </group>
        <group group_id="P2">
          <title>Canola Oil Placebo</title>
          <description>Canola Oil Placebo: 2.5mL per day for 90 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Discontinued Intervention</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement</title>
          <description>Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA)&#xD;
+ Gamma-Linolenic acid (GLA) + Oleic Acid (OA)&#xD;
LCPUFA oil supplement: 2.5mL per day for 90 days&#xD;
Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg</description>
        </group>
        <group group_id="B2">
          <title>Canola Oil Placebo</title>
          <description>Canola Oil Placebo: 2.5mL per day for 90 days</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="15"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="31"/>
          </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="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</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>&gt;=65 years</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>Age</title>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30" lower_limit="25" upper_limit="36"/>
                    <measurement group_id="B2" value="25" lower_limit="23" upper_limit="25"/>
                    <measurement group_id="B3" value="27" lower_limit="23" upper_limit="36"/>
                  </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="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="21"/>
                  </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="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Child Behavior - Pervasive Developmental Disorders Screening Test-II Stage 2</title>
        <description>The Pervasive Developmental Disorders Screening Test-II stage 2 (PDDST-II) is a 14-item measure designed to discriminate Autism Spectrum Disorders from a related non-autistic developmental disorder in children ages 12 to 48 months old. The min score is 0 and the max score is 14. Scores equal to or greater than five yield a positive screen for autism. PDDST-II scores were measured at baseline and then again at study completion (90 days post randomization). The scores were calculated as the PDDST-II value at 90 days minus the PDDST-II value at baseline.</description>
        <time_frame>Baseline to 90 days post randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Long Chain Polyunsaturated Fatty Acid (LCPUFA) Oil Supplement</title>
            <description>Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA)&#xD;
+ Gamma-Linolenic acid (GLA) + Oleic Acid (OA)&#xD;
LCPUFA oil supplement: 2.5mL per day for 90 days&#xD;
Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg</description>
          </group>
          <group group_id="O2">
            <title>Canola Oil Placebo</title>
            <description>Canola Oil Placebo: 2.5mL per day for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Child Behavior - Pervasive Developmental Disorders Screening Test-II Stage 2</title>
          <description>The Pervasive Developmental Disorders Screening Test-II stage 2 (PDDST-II) is a 14-item measure designed to discriminate Autism Spectrum Disorders from a related non-autistic developmental disorder in children ages 12 to 48 months old. The min score is 0 and the max score is 14. Scores equal to or greater than five yield a positive screen for autism. PDDST-II scores were measured at baseline and then again at study completion (90 days post randomization). The scores were calculated as the PDDST-II value at 90 days minus the PDDST-II value at baseline.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" spread="2.6"/>
                    <measurement group_id="O2" value="-0.2" spread="1.9"/>
                  </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>The sample size was determined based on the goal of confirming trial feasibility and estimating effect sizes for a full-scale trial, not for a definitive test of efficacy. The enrollment goal was 40, which would have provided an indication of an expected effect size for a larger full-scale trial (e.g., 53% power to detect a 2-point decrease (approximately 0.7-SD based on a prior study) in Pervasive Developmental Disorders Screening Test-II score). Funding limitations capped enrollment at 31.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Analyses compared the change in Pervasive Developmental Disorders Screening Test-II scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect. Group mean differences divided by the standard deviation were also calculated as effect sizes.</non_inferiority_desc>
            <p_value>0.67</p_value>
            <p_value_desc>Threshold for statistical significance (&lt;0.05)</p_value_desc>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA)</title>
        <description>Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a 42 item tool that is useful for identifying social-emotional problems and/or deficits in children. BITSEA includes the following subscales: Competence (11 Items, min score:0, max score:22), problem behaviors--dysregulation (8 items, min score:0, max score:16) , externalizing (6 items, min score:0, max score:12), internalizing (8 items, min score:0, max score:16), Autism Spectrum Disorder (17 Items, min score:0, max score:34), and Red Flags (14 items, min score:0, max score:28).The questions overlap and the problem subscale is a combination of dysregulation, externalizing, and internalizing. Higher problem scores indicate greater levels of social-emotional/behavioral problems. Lower Competence scores indicate possible delay/deficit. Scores were measured at baseline and then again at study completion (90 days post randomization). The change in BITSEA scores were calculated as the value at 90 days - the value at baseline.</description>
        <time_frame>Baseline to 90 days post randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Long Chain Polyunsaturated Fatty Acids (LCPUFA) Supplement</title>
            <description>Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA)&#xD;
+ Gamma-Linolenic acid (GLA) + Oleic Acid (OA)&#xD;
LCPUFA oil supplement: 2.5mL per day for 90 days&#xD;
Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)</description>
          </group>
          <group group_id="O2">
            <title>Canola Oil Placebo</title>
            <description>Canola Oil Placebo: 2.5mL per day for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA)</title>
          <description>Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a 42 item tool that is useful for identifying social-emotional problems and/or deficits in children. BITSEA includes the following subscales: Competence (11 Items, min score:0, max score:22), problem behaviors--dysregulation (8 items, min score:0, max score:16) , externalizing (6 items, min score:0, max score:12), internalizing (8 items, min score:0, max score:16), Autism Spectrum Disorder (17 Items, min score:0, max score:34), and Red Flags (14 items, min score:0, max score:28).The questions overlap and the problem subscale is a combination of dysregulation, externalizing, and internalizing. Higher problem scores indicate greater levels of social-emotional/behavioral problems. Lower Competence scores indicate possible delay/deficit. Scores were measured at baseline and then again at study completion (90 days post randomization). The change in BITSEA scores were calculated as the value at 90 days - the value at baseline.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Competence</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="3.2"/>
                    <measurement group_id="O2" value="0.9" spread="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Problems</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.2" spread="6.1"/>
                    <measurement group_id="O2" value="-3.2" spread="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dysregulation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="2.3"/>
                    <measurement group_id="O2" value="-0.8" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Externalizing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.3" spread="1.3"/>
                    <measurement group_id="O2" value="-0.7" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Internalizing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="2.3"/>
                    <measurement group_id="O2" value="-0.5" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Austism Spectrum Disorder</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" spread="2.6"/>
                    <measurement group_id="O2" value="0.8" spread="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Red Flag</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.5" spread="3.8"/>
                    <measurement group_id="O2" value="-1.0" spread="2.8"/>
                  </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>The reported p-value is for the comparison of the change in Competence scores between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.</non_inferiority_desc>
            <p_value>0.22</p_value>
            <p_value_desc>Threshold for statistical significance (&lt;0.05).</p_value_desc>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in Problem scores between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Analyses compared the change in the BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes</non_inferiority_desc>
            <p_value>0.92</p_value>
            <p_value_desc>Threshold for statistical significance (&lt;0.05).</p_value_desc>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in Dysregulation scores between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.</non_inferiority_desc>
            <p_value>0.88</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in Externalizing scores between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.</non_inferiority_desc>
            <p_value>0.23</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in Internalizing scores between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.</non_inferiority_desc>
            <p_value>0.91</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in Austism Spectrum Disorder scores between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.</non_inferiority_desc>
            <p_value>0.03</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in Red Flag scores between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Analyses compared the change in BITSEA outcome scores between groups, controlling for baseline scores, using mixed effects regression. This method leverages maximum likelihood to account for missing data. Treatment-by-time interaction terms were included as fixed effects and served as estimates of treatment effect; no participant characteristics were included as covariates in the models. Group mean differences divided by the standard deviation were also calculated as effect sizes.</non_inferiority_desc>
            <p_value>0.07</p_value>
            <method>Mixed Models Analysis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fatty Acid</title>
        <description>The secondary outcome measures in this trial involve an examination of change in fatty acids from the first study visit to the final study visit.</description>
        <time_frame>Baseline to 90 days post randomization</time_frame>
        <population>Rows titles are fatty acids with different C:D ratio where, &quot;C&quot; stands for Carbohydrate; &quot;D&quot; stands for Double bond; &quot;C:D&quot; is the ratio of the total amount of Carbon atoms of the fatty acid in relation to the number of double (unsaturated) bonds in it.</population>
        <group_list>
          <group group_id="O1">
            <title>LCPUFA Oil Supplement</title>
            <description>EPA + DHA + GLA + OA oil supplement&#xD;
LCPUFA oil supplement: 2.5mL per day for 90 days&#xD;
Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)</description>
          </group>
          <group group_id="O2">
            <title>Canola Oil Placebo</title>
            <description>Canola Oil Placebo: 2.5mL per day for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Fatty Acid</title>
          <description>The secondary outcome measures in this trial involve an examination of change in fatty acids from the first study visit to the final study visit.</description>
          <population>Rows titles are fatty acids with different C:D ratio where, &quot;C&quot; stands for Carbohydrate; &quot;D&quot; stands for Double bond; &quot;C:D&quot; is the ratio of the total amount of Carbon atoms of the fatty acid in relation to the number of double (unsaturated) bonds in it.</population>
          <units>nmol/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>10:0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.15" spread="3.23"/>
                    <measurement group_id="O2" value="-4.91" spread="7.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12:0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.56" spread="2.90"/>
                    <measurement group_id="O2" value="-2.43" spread="6.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>14:0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.07" spread="4.62"/>
                    <measurement group_id="O2" value="-8.42" spread="6.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>16:0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="177" spread="99.60"/>
                    <measurement group_id="O2" value="-28.0" spread="116.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>16:1n-7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.83" spread="9.90"/>
                    <measurement group_id="O2" value="27.0" spread="17.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18:0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="138" spread="69.25"/>
                    <measurement group_id="O2" value="-40.3" spread="99.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18:1n-9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.5" spread="46.66"/>
                    <measurement group_id="O2" value="-21.6" spread="50.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18:1n-7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0" spread="4.98"/>
                    <measurement group_id="O2" value="-2.13" spread="6.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18:2n-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.7" spread="69.83"/>
                    <measurement group_id="O2" value="-8.72" spread="56.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18:3n-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.69" spread="2.54"/>
                    <measurement group_id="O2" value="-4.29" spread="5.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18:3n-3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.44" spread="2.19"/>
                    <measurement group_id="O2" value="-3.81" spread="5.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>18:4n-3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.15" spread="1.19"/>
                    <measurement group_id="O2" value="-3.44" spread="3.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20:3n-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.24" spread="9.05"/>
                    <measurement group_id="O2" value="-17.1" spread="15.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20:4n-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.3" spread="57.74"/>
                    <measurement group_id="O2" value="-7.72" spread="70.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>20:5n-3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.7" spread="8.21"/>
                    <measurement group_id="O2" value="-2.73" spread="12.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>22:5n-3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.27" spread="4.88"/>
                    <measurement group_id="O2" value="-2.84" spread="4.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>22:6n-3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109" spread="26.50"/>
                    <measurement group_id="O2" value="-1.44" spread="26.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>total omega-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.9" spread="122.71"/>
                    <measurement group_id="O2" value="-37.9" spread="138.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>total omega-3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="146" spread="34.13"/>
                    <measurement group_id="O2" value="-14.3" spread="43.64"/>
                  </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>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (10:0 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.31</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (12:0 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.47</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (14:0 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.38</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (16:0 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.02</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (16:1n-7 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.16</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:0 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.02</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:1n-9 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.02</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:2n-6 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.21</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:3n-6 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.34</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:3n-3 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.24</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (18:4n-3 nmol/mL ) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.50</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (20:3n-6 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.07</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (20:4n-6 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.10</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (20:5n-3 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.001</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (22:5n-3 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.71</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (22:6n-3 nmol/mL) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.001</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (Total Omega-6) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.10</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The reported p-value is for the comparison of the change in erythrocyte fatty acid composition (total omega-3) between groups (LCPUFA vs. Placebo).</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Differences in mean changes in erythrocyte fatty acid composition were examined using t-tests.</non_inferiority_desc>
            <p_value>0.10</p_value>
            <p_value_desc>P-values &lt;0.05 were considered statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Feasibility: Future Full-scale Multi-site Study</title>
        <description>Feasibility of a future full-scale multi-site study is assessed by examining the number of children screened, the proportion of these children who screen positive for ASD, the number of children who agree to participate in the trial, the number of children who return for the second and third study visits, baseline differences in individual fatty acids between the intervention and comparison groups, and adherence to the assigned treatment.</description>
        <time_frame>Pre-baseline to 90 days post randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>LCPUFA Oil Supplement</title>
            <description>EPA + DHA + GLA + OA oil supplement&#xD;
LCPUFA oil supplement: 2.5mL per day for 90 days&#xD;
Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)</description>
          </group>
          <group group_id="O2">
            <title>Canola Oil Placebo</title>
            <description>Canola Oil Placebo: 2.5mL per day for 90 days</description>
          </group>
        </group_list>
        <measure>
          <title>Feasibility: Future Full-scale Multi-site Study</title>
          <description>Feasibility of a future full-scale multi-site study is assessed by examining the number of children screened, the proportion of these children who screen positive for ASD, the number of children who agree to participate in the trial, the number of children who return for the second and third study visits, baseline differences in individual fatty acids between the intervention and comparison groups, and adherence to the assigned treatment.</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="15"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline to 90 days post randomization</time_frame>
      <desc>Information to be collected includes event description, time of onset, Study Doctor's assessment of severity, relationship to study product,and time of resolution/stabilization of the event. All AEs occurring during study participation must be documented appropriately regardless of relationship.</desc>
      <group_list>
        <group group_id="E1">
          <title>LCPUFA Oil Supplement</title>
          <description>EPA + DHA + GLA + OA oil supplement&#xD;
LCPUFA oil supplement: 2.5mL per day for 90 days&#xD;
Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)</description>
        </group>
        <group group_id="E2">
          <title>Canola Oil Placebo</title>
          <description>Canola Oil Placebo: 2.5mL per day for 90 days</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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="15" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear Nose Throat Symptoms</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal Symptoms</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cold/Fever</sub_title>
                <description>Multi-symptom illnesses reported by caregivers which typically included more than 1 body system and/or fever</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Behavioral Symptoms</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory symptoms</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and Limb Symptoms</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </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. Sarah Keim</name_or_title>
      <organization>Nationwide Children's Hospital</organization>
      <phone>614-722-3177</phone>
      <email>Sarah.Keim@nationwidechildrens.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/NCT01683565
org study id: 752311
nct id: NCT01683565
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The purpose of this study is to examine whether supplementation with certain polyunsaturated
      fatty acids can help development and behavior of children born preterm.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Child Behavior - Pervasive Developmental Disorders Screening Test-II Stage 2
time frame: Baseline to 90 days post randomization
description: The Pervasive Developmental Disorders Screening Test-II stage 2 (PDDST-II) is a 14-item measure designed to discriminate Autism Spectrum Disorders from a related non-autistic developmental disorder in children ages 12 to 48 months old. The min score is 0 and the max score is 14. Scores equal to or greater than five yield a positive screen for autism. PDDST-II scores were measured at baseline and then again at study completion (90 days post randomization). The scores were calculated as the PDDST-II value at 90 days minus the PDDST-II value at baseline.
measure: Child Behavior-Brief Infant-Toddler Social and Emotional Assessment (BITSEA)
time frame: Baseline to 90 days post randomization
description: Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is a 42 item tool that is useful for identifying social-emotional problems and/or deficits in children. BITSEA includes the following subscales: Competence (11 Items, min score:0, max score:22), problem behaviors--dysregulation (8 items, min score:0, max score:16) , externalizing (6 items, min score:0, max score:12), internalizing (8 items, min score:0, max score:16), Autism Spectrum Disorder (17 Items, min score:0, max score:34), and Red Flags (14 items, min score:0, max score:28).The questions overlap and the problem subscale is a combination of dysregulation, externalizing, and internalizing. Higher problem scores indicate greater levels of social-emotional/behavioral problems. Lower Competence scores indicate possible delay/deficit. Scores were measured at baseline and then again at study completion (90 days post randomization). The change in BITSEA scores were calculated as the value at 90 days - the value at baseline.
measure: Fatty Acid
time frame: Baseline to 90 days post randomization
description: The secondary outcome measures in this trial involve an examination of change in fatty acids from the first study visit to the final study visit.
measure: Feasibility: Future Full-scale Multi-site Study
time frame: Pre-baseline to 90 days post randomization
description: Feasibility of a future full-scale multi-site study is assessed by examining the number of children screened, the proportion of these children who screen positive for ASD, the number of children who agree to participate in the trial, the number of children who return for the second and third study visits, baseline differences in individual fatty acids between the intervention and comparison groups, and adherence to the assigned treatment.
arm group label: LCPUFA Oil Supplement
arm group type: Experimental
description: EPA + DHA + GLA + OA oil supplement
arm group label: Canola Oil Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: LCPUFA oil supplement
description: 2.5mL per day for 90 days
Daily Dose: EPA (338mg) + DHA (225mg) + GLA (83mg) + OA (200mg)
arm group label: LCPUFA Oil Supplement
intervention type: Other
intervention name: Canola Oil Placebo
description: 2.5mL per day for 90 days
arm group label: Canola Oil Placebo
criteria: 
gender: All
minimum age: 18 Months
maximum age: 39 Months
healthy volunteers: No
last name: Sarah Keim, PhD
role: Principal Investigator
affiliation: Nationwide Children's Hospital
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Nationwide Children's Hospital
investigator full name: Sarah Keim
investigator title: Principal Investigator
mesh term: Premature Birth
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 