<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/NCT03252522</url>
  </required_header>
  <id_info>
    <org_study_id>16870</org_study_id>
    <nct_id>NCT03252522</nct_id>
  </id_info>
  <brief_title>Micronutrients for Attention-Deficit Hyperactivity Disorder in Youth (MADDY) Study</brief_title>
  <acronym>MADDY</acronym>
  <official_title>Evaluating the Efficacy of Supplementation With Micronutrients for ADHD in Youth (MADDY) Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Lethbridge</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National University of Natural Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Foundation for Excellence in Mental Health Care</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Waterloo Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Oregon Health and Science University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This proposed research will use randomized control trial (RCT) methodology and compare&#xD;
      micronutrients with placebo in 135 children with ADHD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study examines a broad spectrum micronutrient treatment for children with ADHD. The goal&#xD;
      is to broaden the scope of evidence-based treatments, and to address the public desire for&#xD;
      non-pharmacological treatment options. This study will use a randomized controlled trial&#xD;
      design, comparing micronutrients with placebo in 135 children, ages 6-12, with ADHD plus&#xD;
      irritability or anger based on parent-report of symptoms. The study will also collect&#xD;
      biological samples (saliva, stool, urine, hair, and blood) from the children to examine&#xD;
      physiological mechanisms of micronutrient effects. If the micronutrient treatment&#xD;
      successfully diminishes symptoms, the clinical implication is to offer this as a legitimate&#xD;
      non-pharmacological alternative to stimulant medication.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 23, 2018</start_date>
  <completion_date type="Actual">May 31, 2021</completion_date>
  <primary_completion_date type="Actual">July 10, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <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>
    <masking_description>Placebo-controlled; randomization created by statistician, all involved in the study and assessment are blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>CASI-5 Parent-rated Composite Score</measure>
    <time_frame>Baseline and week 8</time_frame>
    <description>Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5). The CASI-5 is based on the DSM-5 symptom criteria. The subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict that will be combined into a total composite score; range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical Global Impression (CGI) - Number of Participants Considered a Treatment Responder (Score of 1 or 2)</measure>
    <time_frame>Week 8</time_frame>
    <description>Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AST, ALT, Alkaline in U/L</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RBC Count in Cells/mcL</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Cell Volume in fL</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Iron in ug/dL</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL</measure>
    <time_frame>Baseline and Week 8</time_frame>
    <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression (CGI)</measure>
    <time_frame>16 weeks</time_frame>
    <description>Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CASI-5 Parent Report</measure>
    <time_frame>Week 16</time_frame>
    <description>Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5) subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict. The CASI-5 is based on the DSM-5 symptom criteria. Item range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome. The subscales for ADHD, ODD, and DMD will be composite scores.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">135</enrollment>
  <condition>Attention Deficit Hyperactivity Disorder</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Capsules of inactive placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open Label</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants have the option to participate in an 8-week, naturalistic, open label follow-up in which the child will take the active micronutrient treatment; capsules of broad spectrum micronutrients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants</intervention_name>
    <description>60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_label>Open Label</arm_group_label>
    <other_name>Daily Essential Nutrients (DEN)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age inclusive of and between 6 and 12 years at the time of enrollment.&#xD;
&#xD;
          -  Verbally willing to swallowing a maximum of 9-12 capsules/day with food, attend all&#xD;
             study appointments and complete questionnaires.&#xD;
&#xD;
          -  Meet criteria for ADHD as assessed by the clinical cut-off (6+ questions scored as 2's&#xD;
             or 3's, &quot;often,&quot; or &quot;very often&quot;) on the Category A: ADHD questions from on the Child&#xD;
             &amp; Adolescent Symptom Inventory-5 (CASI-5) with at least several symptoms present in&#xD;
             more than one setting, based on the Diagnostic and Statistical Manual (DSM) 5 symptom&#xD;
             criteria, including significant impairment in functioning socially and/or&#xD;
             academically.&#xD;
&#xD;
          -  Demonstrate at least one symptom of irritability or anger as assessed by a score of 2&#xD;
             or 3 on one question from Category B or Rz from the CASI-5.&#xD;
&#xD;
          -  Be medication-free, or washout with medical supervision to be provided by the child's&#xD;
             pediatrician or primary care physician, reliant on the parent/guardian to work with&#xD;
             that physician, for at least two weeks prior to in-person study assessment. Washout&#xD;
             will be recorded as occurring on the date reported by the parent/guardian, with a&#xD;
             faxed copy of the progress note, visit summary or signed letter from participant's&#xD;
             doctor.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Neurological disorder involving brain or other central function (e.g., history of or&#xD;
             suspected intellectual disability, autism spectrum disorder, epilepsy, multiple&#xD;
             sclerosis, narcolepsy) or other major psychiatric condition requiring hospitalization&#xD;
             (e.g. significant mood disorder, active suicidal ideation, or psychosis), based on&#xD;
             parent/guardian self-report of child's condition and responses to category M on the&#xD;
             CASI-5 subscale.&#xD;
&#xD;
          -  Any serious medical condition, including inflammatory bowel disease, history of&#xD;
             cancer, kidney or liver disease, hyperthyroidism, diabetes Type I or II.&#xD;
&#xD;
          -  Known allergy to any ingredients of the intervention.&#xD;
&#xD;
          -  Any known abnormality of mineral metabolism (e.g., Wilson's disease, hemochromatosis).&#xD;
&#xD;
          -  Taking any other medication with primarily central nervous system activity, including&#xD;
             stimulants, within the last two weeks prior to in-person assessment; participants must&#xD;
             be off these medications for a minimum of two weeks prior to the screening.&#xD;
&#xD;
          -  Severe separation anxiety that would preclude separating from parent/guardian to&#xD;
             answer study questionnaires.&#xD;
&#xD;
          -  Any disability that would interfere with participant answering questions verbally.&#xD;
&#xD;
          -  Non-English speaking.&#xD;
&#xD;
          -  Pregnancy or sexually active at baseline. Exclusion criteria 1-6 and 9, will be based&#xD;
             on parent/guardian self-report of child's condition. If the parent/guardian reports&#xD;
             medical exclusion criteria, or concerns about eligibility, data provided by&#xD;
             parent/guardian will be confirmed by review of medical records with release of&#xD;
             information signed by parent/guardian. Potential participant may be reviewed in-person&#xD;
             by a study physician in the case of any concerns about participation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeanette Johnstone</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oregon Health and Science University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Lethbridge</name>
      <address>
        <city>Lethbridge</city>
        <state>Alberta</state>
        <zip>AB T1K 6T5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <results_first_submitted>December 1, 2021</results_first_submitted>
  <results_first_submitted_qc>January 13, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">February 9, 2022</results_first_posted>
  <disposition_first_submitted>July 1, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>January 13, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">February 9, 2022</disposition_first_posted>
  <last_update_submitted>January 11, 2023</last_update_submitted>
  <last_update_submitted_qc>January 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oregon Health and Science University</investigator_affiliation>
    <investigator_full_name>Jeanette Johnstone</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>ADHD</keyword>
  <keyword>ODD</keyword>
  <keyword>DMDD</keyword>
  <keyword>Inattention</keyword>
  <keyword>Impulsivity</keyword>
  <keyword>Irritability</keyword>
  <keyword>Anger</keyword>
  <keyword>Micronutrients</keyword>
  <keyword>Emotional Dysregulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperkinesis</mesh_term>
    <mesh_term>Attention Deficit Disorder with Hyperactivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Micronutrients</mesh_term>
    <mesh_term>Trace Elements</mesh_term>
    <mesh_term>Antioxidants</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>February 23, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/22/NCT03252522/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Intervention</title>
          <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
        </group>
        <group group_id="P3">
          <title>Open Label</title>
          <description>All participants have the option to participate in an 8-week, naturalistic, open label follow-up in which the child will take the active micronutrient treatment; capsules of broad spectrum micronutrients.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Phase 1: Intervention &amp; Placebo</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="78"/>
                <participants group_id="P2" count="57"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="69"/>
                <participants group_id="P2" count="54"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unable to swallow pills</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Commenced stimulant medication</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Phase 2: Open Label</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="123"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="99"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="24"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Commenced stimulant medication</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intervention</title>
          <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</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="78"/>
            <count group_id="B2" value="57"/>
            <count group_id="B3" value="135"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="78"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="135"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="78"/>
                    <measurement group_id="B2" value="57"/>
                    <measurement group_id="B3" value="135"/>
                  </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>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="78"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="135"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="57"/>
                    <measurement group_id="B2" value="35"/>
                    <measurement group_id="B3" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>&quot;Other&quot; ethnicity includes Jewish, Japanese, European, Metis, Canadian, or other/not specified</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ethnicity</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="78"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="135"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="85"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown/Did Not Report</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <description>&quot;Other&quot; includes American Indian/Native American or Alaska Native, Metis, Native Hawaiian/Pacific Islander, or not specified.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="78"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="135"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>African American/Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="60"/>
                    <measurement group_id="B2" value="45"/>
                    <measurement group_id="B3" value="105"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown/Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <population>Participants included in the ITT analysis.</population>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="71"/>
                    <count group_id="B2" value="55"/>
                    <count group_id="B3" value="126"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="71"/>
                    <count group_id="B2" value="55"/>
                    <count group_id="B3" value="126"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>CASI-5 Parent-rated Composite Score</title>
        <description>Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5). The CASI-5 is based on the DSM-5 symptom criteria. The subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict that will be combined into a total composite score; range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome.</description>
        <time_frame>Baseline and week 8</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>CASI-5 Parent-rated Composite Score</title>
          <description>Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5). The CASI-5 is based on the DSM-5 symptom criteria. The subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict that will be combined into a total composite score; range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.49" spread="0.08"/>
                    <measurement group_id="O2" value="1.52" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.18" spread="0.08"/>
                    <measurement group_id="O2" value="1.23" spread="0.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Clinical Global Impression (CGI) - Number of Participants Considered a Treatment Responder (Score of 1 or 2)</title>
        <description>Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline.</description>
        <time_frame>Week 8</time_frame>
        <population>Participants considered in the ITT analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impression (CGI) - Number of Participants Considered a Treatment Responder (Score of 1 or 2)</title>
          <description>Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline.</description>
          <population>Participants considered in the ITT analysis</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="55"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L</title>
        <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention (Baseline)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Intervention (Week 8)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Baseline)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo (Week 8)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L</title>
          <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
          <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="38"/>
                <count group_id="O4" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Sodium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="139.13" spread="0.34"/>
                    <measurement group_id="O2" value="139.16" spread="0.34"/>
                    <measurement group_id="O3" value="139.28" spread="0.36"/>
                    <measurement group_id="O4" value="139.42" spread="0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" spread="0.10"/>
                    <measurement group_id="O2" value="4.06" spread="0.10"/>
                    <measurement group_id="O3" value="4.09" spread="0.10"/>
                    <measurement group_id="O4" value="4.0" spread="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chloride</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="105.07" spread="0.96"/>
                    <measurement group_id="O2" value="104.81" spread="0.97"/>
                    <measurement group_id="O3" value="104.88" spread="0.97"/>
                    <measurement group_id="O4" value="105.28" spread="0.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Carbon dioxide</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.62" spread="0.21"/>
                    <measurement group_id="O2" value="25.64" spread="0.22"/>
                    <measurement group_id="O3" value="25.97" spread="0.24"/>
                    <measurement group_id="O4" value="25.86" spread="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anion gap</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.30" spread="2.83"/>
                    <measurement group_id="O2" value="10.64" spread="2.83"/>
                    <measurement group_id="O3" value="10.31" spread="2.83"/>
                    <measurement group_id="O4" value="10.15" spread="2.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL</title>
        <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention (Baseline)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Intervention (Week 8)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Baseline)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo (Week 8)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL</title>
          <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
          <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="38"/>
                <count group_id="O4" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Calcium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.47" spread="0.20"/>
                    <measurement group_id="O2" value="9.49" spread="0.20"/>
                    <measurement group_id="O3" value="9.47" spread="0.20"/>
                    <measurement group_id="O4" value="9.40" spread="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood urea nitrogen (BUN)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.48" spread="0.41"/>
                    <measurement group_id="O2" value="13.17" spread="0.42"/>
                    <measurement group_id="O3" value="12.56" spread="0.46"/>
                    <measurement group_id="O4" value="12.13" spread="0.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.46" spread="0.01"/>
                    <measurement group_id="O2" value="0.49" spread="0.01"/>
                    <measurement group_id="O3" value="0.46" spread="0.01"/>
                    <measurement group_id="O4" value="0.46" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.15" spread="2.36"/>
                    <measurement group_id="O2" value="83.03" spread="2.39"/>
                    <measurement group_id="O3" value="79.45" spread="2.44"/>
                    <measurement group_id="O4" value="80.0" spread="2.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin total</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.47" spread="0.03"/>
                    <measurement group_id="O2" value="0.45" spread="0.03"/>
                    <measurement group_id="O3" value="0.49" spread="0.03"/>
                    <measurement group_id="O4" value="0.46" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL</title>
        <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention (Baseline)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Intervention (Week 8)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Baseline)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo (Week 8)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL</title>
          <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
          <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
          <units>g/dL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="38"/>
                <count group_id="O4" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Albumin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.34" spread="0.17"/>
                    <measurement group_id="O2" value="4.34" spread="0.17"/>
                    <measurement group_id="O3" value="4.29" spread="0.17"/>
                    <measurement group_id="O4" value="4.28" spread="0.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total protein</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.15" spread="0.63"/>
                    <measurement group_id="O2" value="8.45" spread="0.65"/>
                    <measurement group_id="O3" value="7.07" spread="0.73"/>
                    <measurement group_id="O4" value="7.06" spread="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.99" spread="0.17"/>
                    <measurement group_id="O2" value="12.96" spread="0.17"/>
                    <measurement group_id="O3" value="12.99" spread="0.18"/>
                    <measurement group_id="O4" value="12.91" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean cell Hgb concentration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.82" spread="0.13"/>
                    <measurement group_id="O2" value="33.59" spread="0.13"/>
                    <measurement group_id="O3" value="33.75" spread="0.15"/>
                    <measurement group_id="O4" value="33.47" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AST, ALT, Alkaline in U/L</title>
        <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention (Baseline)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Intervention (Week 8)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Baseline)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo (Week 8)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>AST, ALT, Alkaline in U/L</title>
          <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
          <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
          <units>U/L</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="38"/>
                <count group_id="O4" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AST</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.58" spread="1.26"/>
                    <measurement group_id="O2" value="27.28" spread="1.28"/>
                    <measurement group_id="O3" value="25.72" spread="1.42"/>
                    <measurement group_id="O4" value="22.79" spread="1.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.67" spread="3.25"/>
                    <measurement group_id="O2" value="26.00" spread="3.27"/>
                    <measurement group_id="O3" value="20.40" spread="3.37"/>
                    <measurement group_id="O4" value="18.09" spread="3.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline phosphatase</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="255" spread="8.10"/>
                    <measurement group_id="O2" value="241.33" spread="8.15"/>
                    <measurement group_id="O3" value="252.21" spread="9.29"/>
                    <measurement group_id="O4" value="257.93" spread="9.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>RBC Count in Cells/mcL</title>
        <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention (Baseline)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Intervention (Week 8)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Baseline)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo (Week 8)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>RBC Count in Cells/mcL</title>
          <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
          <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
          <units>cells/mcL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="38"/>
                <count group_id="O4" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4,650,000" spread="0.08"/>
                    <measurement group_id="O2" value="4,650,000" spread="0.08"/>
                    <measurement group_id="O3" value="4,600,000" spread="0.08"/>
                    <measurement group_id="O4" value="4,600,000" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent</title>
        <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention (Baseline)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Intervention (Week 8)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Baseline)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo (Week 8)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent</title>
          <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
          <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
          <units>percent</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="38"/>
                <count group_id="O4" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hematocrit</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.40" spread="0.52"/>
                    <measurement group_id="O2" value="38.60" spread="0.52"/>
                    <measurement group_id="O3" value="38.50" spread="0.55"/>
                    <measurement group_id="O4" value="38.60" spread="0.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RBC distribution</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.03" spread="8.76"/>
                    <measurement group_id="O2" value="25.17" spread="8.76"/>
                    <measurement group_id="O3" value="25.29" spread="8.76"/>
                    <measurement group_id="O4" value="25.02" spread="8.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Immature grans</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.20" spread="0.02"/>
                    <measurement group_id="O2" value="0.18" spread="0.02"/>
                    <measurement group_id="O3" value="0.24" spread="0.02"/>
                    <measurement group_id="O4" value="0.19" spread="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.63" spread="1.65"/>
                    <measurement group_id="O2" value="43.53" spread="1.66"/>
                    <measurement group_id="O3" value="40.25" spread="1.80"/>
                    <measurement group_id="O4" value="40.65" spread="1.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monocyte</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.03" spread="0.34"/>
                    <measurement group_id="O2" value="8.29" spread="0.34"/>
                    <measurement group_id="O3" value="7.78" spread="0.38"/>
                    <measurement group_id="O4" value="8.35" spread="0.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eosinophil</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.82" spread="0.63"/>
                    <measurement group_id="O2" value="4.03" spread="0.64"/>
                    <measurement group_id="O3" value="6.49" spread="0.73"/>
                    <measurement group_id="O4" value="5.71" spread="0.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Cell Volume in fL</title>
        <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention (Baseline)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Intervention (Week 8)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Baseline)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo (Week 8)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Cell Volume in fL</title>
          <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
          <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
          <units>fL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="38"/>
                <count group_id="O4" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82.70" spread="0.44"/>
                    <measurement group_id="O2" value="83.00" spread="0.45"/>
                    <measurement group_id="O3" value="83.74" spread="0.49"/>
                    <measurement group_id="O4" value="83.85" spread="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Iron in ug/dL</title>
        <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention (Baseline)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Intervention (Week 8)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Baseline)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo (Week 8)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Iron in ug/dL</title>
          <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
          <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
          <units>ug/dL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="38"/>
                <count group_id="O4" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.1" spread="4.65"/>
                    <measurement group_id="O2" value="90.7" spread="4.69"/>
                    <measurement group_id="O3" value="100.5" spread="5.35"/>
                    <measurement group_id="O4" value="95.5" spread="5.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL</title>
        <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
        <time_frame>Baseline and Week 8</time_frame>
        <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Intervention (Baseline)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Intervention (Week 8)</title>
            <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Baseline)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
          <group group_id="O4">
            <title>Placebo (Week 8)</title>
            <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL</title>
          <description>Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.</description>
          <population>Only participants in the US sites provided blood and urine samples. Canadian participants were not required by Health Canada to collect safety blood or urine samples, hence the lower number of participants.</population>
          <units>cells/mcL</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="38"/>
                <count group_id="O4" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>WBC count</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5,710" spread="0.22"/>
                    <measurement group_id="O2" value="5,730" spread="0.23"/>
                    <measurement group_id="O3" value="6,080" spread="0.25"/>
                    <measurement group_id="O4" value="5,990" spread="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute monocyte</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="460" spread="0.02"/>
                    <measurement group_id="O2" value="470" spread="0.02"/>
                    <measurement group_id="O3" value="460" spread="0.02"/>
                    <measurement group_id="O4" value="480" spread="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Absolute eosinophil</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="210" spread="0.04"/>
                    <measurement group_id="O2" value="230" spread="0.04"/>
                    <measurement group_id="O3" value="390" spread="0.04"/>
                    <measurement group_id="O4" value="340" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="289,970" spread="7.54"/>
                    <measurement group_id="O2" value="289,320" spread="7.57"/>
                    <measurement group_id="O3" value="290,160" spread="8.62"/>
                    <measurement group_id="O4" value="295,900" spread="8.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Global Impression (CGI)</title>
        <description>Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline.</description>
        <time_frame>16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Open Label (Week 8 to Week 16)</title>
            <description>All children knowingly received the active intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impression (CGI)</title>
          <description>Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline.</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="103"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CASI-5 Parent Report</title>
        <description>Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5) subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict. The CASI-5 is based on the DSM-5 symptom criteria. Item range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome. The subscales for ADHD, ODD, and DMD will be composite scores.</description>
        <time_frame>Week 16</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Open Label (Week 8 to Week 16)</title>
            <description>All children knowingly received the active intervention</description>
          </group>
        </group_list>
        <measure>
          <title>CASI-5 Parent Report</title>
          <description>Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5) subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict. The CASI-5 is based on the DSM-5 symptom criteria. Item range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome. The subscales for ADHD, ODD, and DMD will be composite scores.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="103"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.14" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.99" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline, week 1, week 4, week 8 and week 16</time_frame>
      <desc>Used the Pediatric Adverse Events Rating Scale (PAERS) to assess treatment emergent adverse events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Intervention</title>
          <description>Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Capsules of inactive placebo.&#xD;
Placebo: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.</description>
        </group>
        <group group_id="E3">
          <title>Open Label</title>
          <description>All participants have the option to participate in an 8-week, naturalistic, open label follow-up in which the child will take the active micronutrient treatment; capsules of broad spectrum micronutrients.&#xD;
Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 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="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </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="22" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="26" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Heart racing or skipping beats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>GI symptoms</sub_title>
                <description>GI symptoms are a combination of discrete participants experiencing stomach ache or cramps, nausea/sick to stomach, throwing up/vomiting, and diarrhea.</description>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Tired/fatigued</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Trouble falling asleep</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Other</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Dizzy or light-headed</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Less hungry</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Lost weight</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Gained weight</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle shaking, stiffness, or cramps</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Tics</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Angry or hostile</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Sad or low mood</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Lack of interest</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Mood swings</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Anxious, tense, or uptight</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Lack of self-control/ impulsive</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Trouble paying attention or concentrating</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Racing thoughts</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Can't sit or stand still</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Tried to hurt himself/ herself</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Hurt someone or something</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Unusually good mood or super happy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin rash or irritation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="69"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Jeanette Johnstone, PhD</name_or_title>
      <organization>Oregon Health &amp; Science University</organization>
      <phone>5034943700</phone>
      <email>jojeanet@ohsu.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/NCT03252522
org study id: 16870
nct id: NCT03252522
lead sponsor: 
collaborator: 
collaborator: 
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has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This proposed research will use randomized control trial (RCT) methodology and compare
      micronutrients with placebo in 135 children with ADHD.
This study examines a broad spectrum micronutrient treatment for children with ADHD. The goal
      is to broaden the scope of evidence-based treatments, and to address the public desire for
      non-pharmacological treatment options. This study will use a randomized controlled trial
      design, comparing micronutrients with placebo in 135 children, ages 6-12, with ADHD plus
      irritability or anger based on parent-report of symptoms. The study will also collect
      biological samples (saliva, stool, urine, hair, and blood) from the children to examine
      physiological mechanisms of micronutrient effects. If the micronutrient treatment
      successfully diminishes symptoms, the clinical implication is to offer this as a legitimate
      non-pharmacological alternative to stimulant medication.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Placebo-controlled; randomization created by statistician, all involved in the study and assessment are blinded
measure: CASI-5 Parent-rated Composite Score
time frame: Baseline and week 8
description: Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5). The CASI-5 is based on the DSM-5 symptom criteria. The subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict that will be combined into a total composite score; range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome.
measure: Clinical Global Impression (CGI) - Number of Participants Considered a Treatment Responder (Score of 1 or 2)
time frame: Week 8
description: Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline.
measure: Sodium, Potassium, Chloride, Carbon Dioxide, and Anion Gap in mmol/L
time frame: Baseline and Week 8
description: Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
measure: Calcium, Blood Urea Nitrogen, Creatinine, Glucose, Bilirubin Total in mg/dL
time frame: Baseline and Week 8
description: Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
measure: Albumin, Total Protein, Hemoglobin, Mean Cell Hgb in g/dL
time frame: Baseline and Week 8
description: Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
measure: AST, ALT, Alkaline in U/L
time frame: Baseline and Week 8
description: Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
measure: RBC Count in Cells/mcL
time frame: Baseline and Week 8
description: Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
measure: Hematocrit, RBC Distribution, Immature Grans, Lymphocyte, Monocyte, Eosinophil in Percent
time frame: Baseline and Week 8
description: Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
measure: Mean Cell Volume in fL
time frame: Baseline and Week 8
description: Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
measure: Iron in ug/dL
time frame: Baseline and Week 8
description: Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
measure: WBC Count, Absolute Monocyte, Absolute Eosinophil, Platelet Count in Cells/mcL
time frame: Baseline and Week 8
description: Collect blood and urine samples at two time points. The samples are being collected per a request from the FDA for safety screening.
measure: Clinical Global Impression (CGI)
time frame: 16 weeks
description: Second primary measure is the blinded clinician-rated CGI-Improvement (CGI-I) is a subscale of the CGI that rates overall improvement of symptoms based on all relevant data. Item range is 1-7 (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse); lower score is better. A treatment responder is defined as a participant who is rated a 1 or 2 on the CGI-I. The CGI-Severity (CGI-S) subscale will also be scored at baseline and week 8, with scores compared at the two time points. Item range is 1-7 (normal, borderline ill, mildly ill, moderately ill, markedly ill, severely ill, among the most extremely ill patients); lower score is better; most participants will be a 4 or 5 at baseline.
measure: CASI-5 Parent Report
time frame: Week 16
description: Primary outcome measure, defined a priori, reflecting the often-comorbid ADHD symptoms of emotional dysregulation irritable mood, anger or aggression), are the parent-rated Child and Adolescent Symptom Inventory (CASI-5) subscales of ADHD, Oppositional Defiant Disorder (ODD), Disruptive Mood Dysregulation Disorder (DMDD) and peer conflict. The CASI-5 is based on the DSM-5 symptom criteria. Item range is 0-3 (never, sometimes, often, very often). Higher scores represent a worse outcome. The subscales for ADHD, ODD, and DMD will be composite scores.
arm group label: Intervention
arm group type: Experimental
description: Capsules of broad spectrum micronutrients: a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants.
arm group label: Placebo
arm group type: Placebo Comparator
description: Capsules of inactive placebo.
arm group label: Open Label
arm group type: Experimental
description: All participants have the option to participate in an 8-week, naturalistic, open label follow-up in which the child will take the active micronutrient treatment; capsules of broad spectrum micronutrients.
intervention type: Combination Product
intervention name: Broad Spectrum Micronutrients; a 36-ingredient blend of vitamins, minerals, amino acids, and antioxidants
description: 60% of participants will take 3-4 capsules of broad spectrum micronutrients three times per day for eight weeks. Following the initial 8 weeks (of the RCT), all participants will have the option to participate in an open label extension, during which time the child would take the active micronutrient treatment for 8 weeks
arm group label: Intervention
arm group label: Open Label
other name: Daily Essential Nutrients (DEN)
intervention type: Dietary Supplement
intervention name: Placebo
description: 40% of participants will take 3-4 capsules of inactive placebo three times per day for eight weeks.
arm group label: Placebo
criteria: 
gender: All
minimum age: 6 Years
maximum age: 12 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jeanette Johnstone
role: Principal Investigator
affiliation: Oregon Health and Science University
facility: 
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country: Canada
country: United States
responsible party type: Principal Investigator
investigator affiliation: Oregon Health and Science University
investigator full name: Jeanette Johnstone
investigator title: Principal Investigator
mesh term: Hyperkinesis
mesh term: Attention Deficit Disorder with Hyperactivity
mesh term: Micronutrients
mesh term: Trace Elements
mesh term: Antioxidants
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 