<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/NCT01700959</url>
  </required_header>
  <id_info>
    <org_study_id>MIND</org_study_id>
    <secondary_id>P30CA021765</secondary_id>
    <secondary_id>NCI-2012-02053</secondary_id>
    <nct_id>NCT01700959</nct_id>
  </id_info>
  <brief_title>Melatonin Intervention For Neurocognitive Deficits in the St. Jude Lifetime Cohort</brief_title>
  <official_title>Melatonin Intervention For Neurocognitive Deficits in the St. Jude Lifetime Cohort</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Jude Children's Research Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Jude Children's Research Hospital</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>
      Primary objective:&#xD;
&#xD;
        1. To examine the efficacy of melatonin treatment on neurocognitive functioning in adult&#xD;
           survivors of childhood cancer.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
        1. To evaluate the efficacy of melatonin treatment on delayed sleep onset latency in&#xD;
           long-term childhood cancer survivors.&#xD;
&#xD;
        2. To investigate whether improvement in sleep onset latency due to melatonin treatment is&#xD;
           associated with neurocognitive improvement in long-term childhood cancer survivors.&#xD;
&#xD;
      This study is a randomized double-blind placebo controlled trial of time release melatonin&#xD;
      for adult survivors of childhood cancer who demonstrate impaired neurocognitive functioning&#xD;
      and/or difficulty falling asleep.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All participants undergo a general neurocognitive evaluation at baseline and 6-month&#xD;
      follow-up, focused on assessment of intelligence, academic skills, attention, processing&#xD;
      speed, memory and executive functions.&#xD;
&#xD;
      Sleep parameters using self-report and actigraphy will be assessed at three time points&#xD;
      during the study: Baseline, 3-months, and 6-months.&#xD;
&#xD;
      Participants will be divided into 3 mutually exclusive groups:&#xD;
&#xD;
        -  Cohort 1: Participant has neurocognitive impairment defined as performance on at least&#xD;
           one measure of attention, memory, and/or executive functioning at or below the 10th&#xD;
           percentile, AND is absent of delayed sleep onset latency defined as an inability to fall&#xD;
           asleep within 30 minutes less than once a week during the past month.&#xD;
&#xD;
        -  Cohort 2: Participant has neurocognitive impairment defined as performance on at least&#xD;
           one measure of attention, memory, and/or executive functioning at or below the 10th&#xD;
           percentile, AND has delayed sleep onset latency defined as self-report of an inability&#xD;
           to fall asleep within 30 minutes at least once a week during the past month.&#xD;
&#xD;
        -  Cohort 3: Participant is absent of neurocognitive impairment defined as performance&#xD;
           &gt;10th percentile on all six measures of attention, memory, and executive functioning,&#xD;
           AND has delayed sleep onset latency defined as self-report of an inability to fall&#xD;
           asleep within 30 minutes &gt; once a week during the past month.&#xD;
&#xD;
      Within each group, participants will be randomly assigned to take either 3 mgs of time&#xD;
      release melatonin or placebo 1-2 hours before bedtime each night for 6 months.&#xD;
&#xD;
      Psychosocial measures of health-related quality of life and psychological distress will be&#xD;
      completed at baseline and following 6 months of melatonin/placebo treatment.&#xD;
&#xD;
      Biological samples for serum melatonin levels will be collected at baseline and at the 6&#xD;
      month follow-up evaluation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 6, 2013</start_date>
  <completion_date type="Actual">April 19, 2017</completion_date>
  <primary_completion_date type="Actual">April 19, 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function.</measure>
    <time_frame>Baseline and 6 months after start of therapy</time_frame>
    <description>Efficacy of melatonin treatment on neurocognitive functioning in adult survivors of childhood cancer (Cohorts 1 and 2 only). The measures were analyzed to compare change in neurocognitive performance from baseline to 6 months between active treatment and placebo groups. The unit of measure is a standardized z-score with a mean of 0 and standard deviation of 1. A higher z-score represents a better outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sleep Onset Latency as Measured by Actigraphy and Self-report.</measure>
    <time_frame>Baseline and six months after start of therapy</time_frame>
    <description>Efficacy of melatonin on delayed sleep onset latency in long-term childhood cancer survivors (Cohorts 2 and 3 only). The measures were analyzed to compare change in sleep onset latency from baseline to 6 months between active treatment and placebo groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function, and Sleep Onset Latency as Measured by Actigraphy and Self-report.</measure>
    <time_frame>Baseline and six months after start of therapy</time_frame>
    <description>Investigate whether improvement in sleep onset latency due to melatonin treatment is associated with neurocognitive improvement in long-term childhood cancer survivors (Cohort 2). The change in neurocognitive performance from baseline to 6 months will be examined in relation to change in sleep onset latency. The unit of measure is a standardized z-score with a mean of 0 and standard deviation of 1. The unit of measurement is a correlation coefficient (Pearson's R2). The range is from -1.0 to 1.0. A zero indicates no correlation while values closer to -1.0 or 1.0 reflect a stronger association. A negative correlation suggests that as sleep latency decreased, neurocognitive functioning improved.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">911</enrollment>
  <condition>Cancer Malignancies</condition>
  <arm_group>
    <arm_group_label>Melatonin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>melatonin</intervention_name>
    <description>Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
    <arm_group_label>Melatonin</arm_group_label>
    <other_name>N-Acetyl-5-Methoxytryptamine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Placebo tablets to match the melatonin will be comprised of inert substances.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A St. Jude Life participant who was previously treated at St. Jude Children's Research&#xD;
             Hospital&#xD;
&#xD;
          -  10 or more years from diagnosis&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
          -  Able to speak and understand the English language&#xD;
&#xD;
          -  Participant has a full scale intelligence quotient (FSIQ) score &gt;79.&#xD;
&#xD;
          -  Cohort 1 participant:&#xD;
&#xD;
               -  Has neurocognitive impairment defined as performance on at least one measure of&#xD;
                  attention, memory, and/or executive functioning ≤10th percentile.&#xD;
&#xD;
               -  Is absent of delayed sleep onset latency defined as an inability to fall asleep&#xD;
                  within 30 minutes &lt; once a week during the past month.&#xD;
&#xD;
          -  Cohort 2 participant:&#xD;
&#xD;
               -  Has neurocognitive impairment defined as performance on at least one measure of&#xD;
                  attention, memory, and/or executive functioning ≤10th percentile.&#xD;
&#xD;
               -  Has delayed sleep onset latency defined as self-report of an inability to fall&#xD;
                  asleep within 30 minutes ≥ once a week during the past month.&#xD;
&#xD;
          -  Cohort 3 participant:&#xD;
&#xD;
               -  Is absent of neurocognitive impairment defined as performance &gt;10th percentile on&#xD;
                  all six measures of attention, memory, and executive functioning.&#xD;
&#xD;
               -  Has delayed sleep onset latency defined as self-report of an inability to fall&#xD;
                  asleep within 30 minutes ≥ once a week during the past month.&#xD;
&#xD;
          -  Female participant of childbearing age must not be pregnant or lactating&#xD;
&#xD;
          -  Female research participant of childbearing age and male research participant of child&#xD;
             fathering potential agrees to use safe contraceptive methods&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergy to melatonin or any ingredients of the study product or placebo&#xD;
&#xD;
          -  Participant currently is taking melatonin&#xD;
&#xD;
          -  Known sleep apnea or medically treated sleep disorder (e.g. restless leg syndrome)&#xD;
&#xD;
          -  Known diabetes mellitus - insulin treated&#xD;
&#xD;
          -  Participant has uncontrolled seizure disorder in past 12 months&#xD;
&#xD;
          -  Reported current illicit drug or alcohol abuse or dependence&#xD;
&#xD;
          -  Reported current major psychiatric illness (i.e. schizophrenia, bipolar disorder)&#xD;
&#xD;
          -  Current treatment with: (1) benzodiazepines or other central nervous system&#xD;
             depressants, (2) fluvoxamine, (3) anticoagulants (e.g. coumadin), (4)&#xD;
             immunosuppressant or corticosteroids, OR (5) nifedipine (Procardia XL(R))&#xD;
&#xD;
          -  Employed in a position that requires night work (i.e. 10pm to 6am)&#xD;
&#xD;
          -  Females who are pregnant or lactating/nursing&#xD;
&#xD;
          -  History of neurologic event (i.e. traumatic brain injury) unrelated to cancer or its&#xD;
             treatment&#xD;
&#xD;
          -  Sensory impairment (vision, hearing) that prohibits completion of neurocognitive&#xD;
             examination&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tara Brinkman, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Jude Children's Research Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Jude Children's Research Hospital</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.stjude.org</url>
    <description>St. Jude Children's Research Hospital</description>
  </link>
  <link>
    <url>http://www.stjude.org/protocols</url>
    <description>Clinical Trials Open at St. Jude</description>
  </link>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>September 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <results_first_submitted>March 29, 2018</results_first_submitted>
  <results_first_submitted_qc>June 26, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">June 28, 2018</results_first_posted>
  <last_update_submitted>June 26, 2018</last_update_submitted>
  <last_update_submitted_qc>June 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Melatonin</keyword>
  <keyword>Neurocognitive impairment</keyword>
  <keyword>Sleep disturbance</keyword>
  <keyword>Childhood cancer survivors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <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>October 11, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT01700959/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>911 participants were enrolled and screened between February 2013 and June 2017. Of the 911, 298 were ineligible and 33 withdrew prior to randomization. 580 were randomized.</recruitment_details>
      <pre_assignment_details>The remaining 580 participants were categorized into three mutually exclusive groups: (1) neurocognitive impairment (NI) without delayed sleep onset latency (DSOL), (2) NI with DSOL, and (3) No NI with DSOL. Participants were then randomized to take melatonin or placebo.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Melatonin: NI Without DSOL</title>
          <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
        </group>
        <group group_id="P2">
          <title>Placebo: NI Without DSOL</title>
          <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
        </group>
        <group group_id="P3">
          <title>Melatonin: NI With DSOL</title>
          <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
        </group>
        <group group_id="P4">
          <title>Placebo: NI With DSOL</title>
          <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
        </group>
        <group group_id="P5">
          <title>Melatonin: No NI With DSOL</title>
          <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
        </group>
        <group group_id="P6">
          <title>Placebo: No NI With DSOL</title>
          <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="89"/>
                <participants group_id="P2" count="88"/>
                <participants group_id="P3" count="105"/>
                <participants group_id="P4" count="105"/>
                <participants group_id="P5" count="96"/>
                <participants group_id="P6" count="97"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="62"/>
                <participants group_id="P2" count="64"/>
                <participants group_id="P3" count="65"/>
                <participants group_id="P4" count="70"/>
                <participants group_id="P5" count="69"/>
                <participants group_id="P6" count="72"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="24"/>
                <participants group_id="P3" count="40"/>
                <participants group_id="P4" count="35"/>
                <participants group_id="P5" count="27"/>
                <participants group_id="P6" count="25"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="11"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ineligible</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Noncompliant</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="17"/>
                <participants group_id="P4" count="18"/>
                <participants group_id="P5" count="15"/>
                <participants group_id="P6" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Side effects</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="4"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Analysis based on intent to treat. Include participants who were randomized and completed the 6-month assessment.</population>
      <group_list>
        <group group_id="B1">
          <title>Melatonin: NI Without DSOL</title>
          <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
        </group>
        <group group_id="B2">
          <title>Placebo: NI Without DSOL</title>
          <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
        </group>
        <group group_id="B3">
          <title>Melatonin: NI With DSOL</title>
          <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
        </group>
        <group group_id="B4">
          <title>Placebo: NI With DSOL</title>
          <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
        </group>
        <group group_id="B5">
          <title>Melatonin: No NI With DSOL</title>
          <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
        </group>
        <group group_id="B6">
          <title>Placebo: No NI With DSOL</title>
          <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
        </group>
        <group group_id="B7">
          <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="58"/>
            <count group_id="B2" value="58"/>
            <count group_id="B3" value="62"/>
            <count group_id="B4" value="68"/>
            <count group_id="B5" value="66"/>
            <count group_id="B6" value="68"/>
            <count group_id="B7" value="380"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.8" spread="9.1"/>
                    <measurement group_id="B2" value="36.4" spread="8.1"/>
                    <measurement group_id="B3" value="32.8" spread="7.8"/>
                    <measurement group_id="B4" value="32.4" spread="9.3"/>
                    <measurement group_id="B5" value="35.8" spread="9.0"/>
                    <measurement group_id="B6" value="36.5" spread="8.2"/>
                    <measurement group_id="B7" value="34.46" spread="8.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="37"/>
                    <measurement group_id="B4" value="39"/>
                    <measurement group_id="B5" value="35"/>
                    <measurement group_id="B6" value="46"/>
                    <measurement group_id="B7" value="207"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="29"/>
                    <measurement group_id="B5" value="31"/>
                    <measurement group_id="B6" value="22"/>
                    <measurement group_id="B7" value="173"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="59"/>
                    <measurement group_id="B4" value="61"/>
                    <measurement group_id="B5" value="59"/>
                    <measurement group_id="B6" value="61"/>
                    <measurement group_id="B7" value="347"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="7"/>
                    <measurement group_id="B7" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="7"/>
                    <measurement group_id="B7" value="36"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="53"/>
                    <measurement group_id="B4" value="59"/>
                    <measurement group_id="B5" value="62"/>
                    <measurement group_id="B6" value="59"/>
                    <measurement group_id="B7" value="338"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function.</title>
        <description>Efficacy of melatonin treatment on neurocognitive functioning in adult survivors of childhood cancer (Cohorts 1 and 2 only). The measures were analyzed to compare change in neurocognitive performance from baseline to 6 months between active treatment and placebo groups. The unit of measure is a standardized z-score with a mean of 0 and standard deviation of 1. A higher z-score represents a better outcome.</description>
        <time_frame>Baseline and 6 months after start of therapy</time_frame>
        <population>Analysis based on intent to treat. Include participants who were randomized and completed the 6-month assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Melatonin: NI Without DSOL</title>
            <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
          </group>
          <group group_id="O2">
            <title>Placebo: NI Without DSOL</title>
            <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
          </group>
          <group group_id="O3">
            <title>Melatonin: NI With DSOL</title>
            <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
          </group>
          <group group_id="O4">
            <title>Placebo: NI With DSOL</title>
            <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
          </group>
          <group group_id="O5">
            <title>Melatonin: No NI With DSOL</title>
            <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
          </group>
          <group group_id="O6">
            <title>Placebo: No NI With DSOL</title>
            <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
          </group>
        </group_list>
        <measure>
          <title>Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function.</title>
          <description>Efficacy of melatonin treatment on neurocognitive functioning in adult survivors of childhood cancer (Cohorts 1 and 2 only). The measures were analyzed to compare change in neurocognitive performance from baseline to 6 months between active treatment and placebo groups. The unit of measure is a standardized z-score with a mean of 0 and standard deviation of 1. A higher z-score represents a better outcome.</description>
          <population>Analysis based on intent to treat. Include participants who were randomized and completed the 6-month assessment.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="58"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="68"/>
                <count group_id="O5" value="0"/>
                <count group_id="O6" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Auditory Attention Difference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.35" spread="1.02"/>
                    <measurement group_id="O2" value="0.18" spread="0.87"/>
                    <measurement group_id="O3" value="0.06" spread="1.11"/>
                    <measurement group_id="O4" value="0.37" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sustained Attention Difference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" spread="1.11"/>
                    <measurement group_id="O2" value="0.16" spread="1.30"/>
                    <measurement group_id="O3" value="0.24" spread="1.16"/>
                    <measurement group_id="O4" value="0.08" spread="1.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Working Memory Difference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.17" spread="0.67"/>
                    <measurement group_id="O2" value="0.07" spread="0.82"/>
                    <measurement group_id="O3" value="0.03" spread="0.75"/>
                    <measurement group_id="O4" value="0.004" spread="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Long-term Verbal Memory Difference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.02" spread="1.16"/>
                    <measurement group_id="O2" value="-0.03" spread="1.04"/>
                    <measurement group_id="O3" value="-0.13" spread="0.98"/>
                    <measurement group_id="O4" value="-0.15" spread="1.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cognitive Flexibility</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.31" spread="1.22"/>
                    <measurement group_id="O2" value="0.31" spread="1.060"/>
                    <measurement group_id="O3" value="0.31" spread="1.37"/>
                    <measurement group_id="O4" value="0.18" spread="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cognitive Fluency Difference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.14" spread="0.68"/>
                    <measurement group_id="O2" value="0.21" spread="0.74"/>
                    <measurement group_id="O3" value="0.16" spread="0.64"/>
                    <measurement group_id="O4" value="0.18" spread="0.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sleep Onset Latency as Measured by Actigraphy and Self-report.</title>
        <description>Efficacy of melatonin on delayed sleep onset latency in long-term childhood cancer survivors (Cohorts 2 and 3 only). The measures were analyzed to compare change in sleep onset latency from baseline to 6 months between active treatment and placebo groups.</description>
        <time_frame>Baseline and six months after start of therapy</time_frame>
        <population>Analysis based on intent to treat. Includes participants who were randomized and completed the 6-month assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Melatonin: NI Without DSOL</title>
            <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
          </group>
          <group group_id="O2">
            <title>Placebo: NI Without DSOL</title>
            <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
          </group>
          <group group_id="O3">
            <title>Melatonin: NI With DSOL</title>
            <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
          </group>
          <group group_id="O4">
            <title>Placebo: NI With DSOL</title>
            <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
          </group>
          <group group_id="O5">
            <title>Melatonin: No NI With DSOL</title>
            <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
          </group>
          <group group_id="O6">
            <title>Placebo: No NI With DSOL</title>
            <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
          </group>
        </group_list>
        <measure>
          <title>Sleep Onset Latency as Measured by Actigraphy and Self-report.</title>
          <description>Efficacy of melatonin on delayed sleep onset latency in long-term childhood cancer survivors (Cohorts 2 and 3 only). The measures were analyzed to compare change in sleep onset latency from baseline to 6 months between active treatment and placebo groups.</description>
          <population>Analysis based on intent to treat. Includes participants who were randomized and completed the 6-month assessment.</population>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="68"/>
                <count group_id="O5" value="66"/>
                <count group_id="O6" value="68"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Sleep onset latency - actigraphy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="5.66" spread="29.70"/>
                    <measurement group_id="O4" value="-10.96" spread="30.21"/>
                    <measurement group_id="O5" value="-8.47" spread="23.95"/>
                    <measurement group_id="O6" value="1.95" spread="39.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleet onset latency - self-report</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O3" value="-20.59" spread="23.73"/>
                    <measurement group_id="O4" value="17.79" spread="37.19"/>
                    <measurement group_id="O5" value="-18.14" spread="27.06"/>
                    <measurement group_id="O6" value="-29.03" spread="64.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function, and Sleep Onset Latency as Measured by Actigraphy and Self-report.</title>
        <description>Investigate whether improvement in sleep onset latency due to melatonin treatment is associated with neurocognitive improvement in long-term childhood cancer survivors (Cohort 2). The change in neurocognitive performance from baseline to 6 months will be examined in relation to change in sleep onset latency. The unit of measure is a standardized z-score with a mean of 0 and standard deviation of 1. The unit of measurement is a correlation coefficient (Pearson's R2). The range is from -1.0 to 1.0. A zero indicates no correlation while values closer to -1.0 or 1.0 reflect a stronger association. A negative correlation suggests that as sleep latency decreased, neurocognitive functioning improved.</description>
        <time_frame>Baseline and six months after start of therapy</time_frame>
        <population>Analysis based on intent to treat includes Cohort 2 participants randomized to melatonin who completed the 6-month assessment. Cohorts 1 and 3 were not assessed. 2 assessments of the primary outcome collected in Cohort 2 included self-report and actigraphy. 50 is the total number with actigraphy data. Data were missing for 12 participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Melatonin: NI With DSOL (Actigraphy)</title>
            <description>Data by participant actigraphy. Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
          </group>
          <group group_id="O2">
            <title>Melatonin: NI With DSOL (Self-report)</title>
            <description>Data by participant self-report. Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
          </group>
        </group_list>
        <measure>
          <title>Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function, and Sleep Onset Latency as Measured by Actigraphy and Self-report.</title>
          <description>Investigate whether improvement in sleep onset latency due to melatonin treatment is associated with neurocognitive improvement in long-term childhood cancer survivors (Cohort 2). The change in neurocognitive performance from baseline to 6 months will be examined in relation to change in sleep onset latency. The unit of measure is a standardized z-score with a mean of 0 and standard deviation of 1. The unit of measurement is a correlation coefficient (Pearson's R2). The range is from -1.0 to 1.0. A zero indicates no correlation while values closer to -1.0 or 1.0 reflect a stronger association. A negative correlation suggests that as sleep latency decreased, neurocognitive functioning improved.</description>
          <population>Analysis based on intent to treat includes Cohort 2 participants randomized to melatonin who completed the 6-month assessment. Cohorts 1 and 3 were not assessed. 2 assessments of the primary outcome collected in Cohort 2 included self-report and actigraphy. 50 is the total number with actigraphy data. Data were missing for 12 participants.</population>
          <units>Z-score</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Auditory Attention Difference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.22"/>
                    <measurement group_id="O2" value="-0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sustained Attention Difference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.10"/>
                    <measurement group_id="O2" value="-0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Working Memory Difference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04"/>
                    <measurement group_id="O2" value="-0.001"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Long-term Verbal Memory Difference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.07"/>
                    <measurement group_id="O2" value="-0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cognitive Flexibility</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.30"/>
                    <measurement group_id="O2" value="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cognitive Fluency Difference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.22"/>
                    <measurement group_id="O2" value="0.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Participants were contacted at the end of the first week on study drug then biweekly for the duration of the study, up to 7 months later. Adverse event information was collected by participant reporting and direct questioning.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Melatonin: NI Without DSOL</title>
          <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
        </group>
        <group group_id="E2">
          <title>Placebo: NI Without DSOL</title>
          <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
        </group>
        <group group_id="E3">
          <title>Melatonin: NI With DSOL</title>
          <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
        </group>
        <group group_id="E4">
          <title>Placebo: NI With DSOL</title>
          <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
        </group>
        <group group_id="E5">
          <title>Melatonin: No NI With DSOL</title>
          <description>Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime for 6 months.&#xD;
melatonin: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.</description>
        </group>
        <group group_id="E6">
          <title>Placebo: No NI With DSOL</title>
          <description>Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime for 6 months.&#xD;
placebo: Placebo tablets to match the melatonin will be comprised of inert substances.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="62"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="68"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E6" subjects_affected="10" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Esophageal perforation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Gallstones</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Thyroid cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Cervical cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Trabecular cancer in lungs</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Parotid tumor</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="2" subjects_affected="2" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Unintended pregnancy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="68"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E6" events="4" subjects_affected="3" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Concentration impairment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Kidney infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Bladder perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Flu-like symptoms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Maculo-papular rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Esophageal dilation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <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="37" subjects_at_risk="58"/>
                <counts group_id="E2" subjects_affected="37" subjects_at_risk="58"/>
                <counts group_id="E3" subjects_affected="52" subjects_at_risk="62"/>
                <counts group_id="E4" subjects_affected="60" subjects_at_risk="68"/>
                <counts group_id="E5" subjects_affected="57" subjects_at_risk="66"/>
                <counts group_id="E6" subjects_affected="58" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="68"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E6" events="10" subjects_affected="6" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="10" subjects_affected="8" subjects_at_risk="68"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="66"/>
                <counts group_id="E6" events="10" subjects_affected="10" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="62"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="68"/>
                <counts group_id="E5" events="4" subjects_affected="4" subjects_at_risk="66"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="68"/>
                <counts group_id="E5" events="4" subjects_affected="3" subjects_at_risk="66"/>
                <counts group_id="E6" events="5" subjects_affected="5" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="68"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="66"/>
                <counts group_id="E6" events="9" subjects_affected="8" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E3" events="12" subjects_affected="10" subjects_at_risk="62"/>
                <counts group_id="E4" events="9" subjects_affected="9" subjects_at_risk="68"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="66"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E3" events="14" subjects_affected="10" subjects_at_risk="62"/>
                <counts group_id="E4" events="13" subjects_affected="11" subjects_at_risk="68"/>
                <counts group_id="E5" events="25" subjects_affected="14" subjects_at_risk="66"/>
                <counts group_id="E6" events="20" subjects_affected="17" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="58"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E4" events="7" subjects_affected="7" subjects_at_risk="68"/>
                <counts group_id="E5" events="8" subjects_affected="7" subjects_at_risk="66"/>
                <counts group_id="E6" events="15" subjects_affected="13" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="7" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="62"/>
                <counts group_id="E4" events="12" subjects_affected="10" subjects_at_risk="68"/>
                <counts group_id="E5" events="11" subjects_affected="9" subjects_at_risk="66"/>
                <counts group_id="E6" events="12" subjects_affected="11" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="11" subjects_affected="10" subjects_at_risk="58"/>
                <counts group_id="E2" events="20" subjects_affected="13" subjects_at_risk="58"/>
                <counts group_id="E3" events="26" subjects_affected="21" subjects_at_risk="62"/>
                <counts group_id="E4" events="27" subjects_affected="25" subjects_at_risk="68"/>
                <counts group_id="E5" events="23" subjects_affected="21" subjects_at_risk="66"/>
                <counts group_id="E6" events="37" subjects_affected="29" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="62"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="68"/>
                <counts group_id="E5" events="4" subjects_affected="3" subjects_at_risk="66"/>
                <counts group_id="E6" events="7" subjects_affected="7" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E3" events="20" subjects_affected="16" subjects_at_risk="62"/>
                <counts group_id="E4" events="12" subjects_affected="10" subjects_at_risk="68"/>
                <counts group_id="E5" events="12" subjects_affected="12" subjects_at_risk="66"/>
                <counts group_id="E6" events="14" subjects_affected="12" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="20" subjects_affected="15" subjects_at_risk="58"/>
                <counts group_id="E2" events="27" subjects_affected="18" subjects_at_risk="58"/>
                <counts group_id="E3" events="32" subjects_affected="23" subjects_at_risk="62"/>
                <counts group_id="E4" events="32" subjects_affected="27" subjects_at_risk="68"/>
                <counts group_id="E5" events="37" subjects_affected="26" subjects_at_risk="66"/>
                <counts group_id="E6" events="35" subjects_affected="27" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Hypersomnia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E3" events="12" subjects_affected="12" subjects_at_risk="62"/>
                <counts group_id="E4" events="14" subjects_affected="12" subjects_at_risk="68"/>
                <counts group_id="E5" events="9" subjects_affected="8" subjects_at_risk="66"/>
                <counts group_id="E6" events="9" subjects_affected="8" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Nightmares</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="62"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="68"/>
                <counts group_id="E5" events="6" subjects_affected="6" subjects_at_risk="66"/>
                <counts group_id="E6" events="11" subjects_affected="8" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="68"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E6" events="3" subjects_affected="3" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="21" subjects_affected="19" subjects_at_risk="58"/>
                <counts group_id="E2" events="18" subjects_affected="15" subjects_at_risk="58"/>
                <counts group_id="E3" events="24" subjects_affected="23" subjects_at_risk="62"/>
                <counts group_id="E4" events="25" subjects_affected="21" subjects_at_risk="68"/>
                <counts group_id="E5" events="34" subjects_affected="25" subjects_at_risk="66"/>
                <counts group_id="E6" events="36" subjects_affected="29" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E3" events="12" subjects_affected="10" subjects_at_risk="62"/>
                <counts group_id="E4" events="17" subjects_affected="11" subjects_at_risk="68"/>
                <counts group_id="E5" events="11" subjects_affected="10" subjects_at_risk="66"/>
                <counts group_id="E6" events="21" subjects_affected="20" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Delayed orgasm</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="68"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="66"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Incomnia</sub_title>
                <counts group_id="E1" events="16" subjects_affected="11" subjects_at_risk="58"/>
                <counts group_id="E2" events="14" subjects_affected="11" subjects_at_risk="58"/>
                <counts group_id="E3" events="15" subjects_affected="14" subjects_at_risk="62"/>
                <counts group_id="E4" events="21" subjects_affected="20" subjects_at_risk="68"/>
                <counts group_id="E5" events="38" subjects_affected="26" subjects_at_risk="66"/>
                <counts group_id="E6" events="35" subjects_affected="24" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Libido decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="58"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="68"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="66"/>
                <counts group_id="E6" events="9" subjects_affected="9" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="62"/>
                <counts group_id="E4" events="11" subjects_affected="11" subjects_at_risk="68"/>
                <counts group_id="E5" events="10" subjects_affected="9" subjects_at_risk="66"/>
                <counts group_id="E6" events="13" subjects_affected="12" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Concentration impairment</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E2" events="6" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="62"/>
                <counts group_id="E4" events="17" subjects_affected="14" subjects_at_risk="68"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="66"/>
                <counts group_id="E6" events="13" subjects_affected="13" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary frequency</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="62"/>
                <counts group_id="E4" events="9" subjects_affected="9" subjects_at_risk="68"/>
                <counts group_id="E5" events="7" subjects_affected="7" subjects_at_risk="66"/>
                <counts group_id="E6" events="6" subjects_affected="6" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Erectile dysfunction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="68"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="66"/>
                <counts group_id="E6" events="1" subjects_affected="1" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Irregular menstruation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="62"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="68"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="66"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="4" subjects_affected="4" subjects_at_risk="68"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="66"/>
                <counts group_id="E6" events="0" subjects_affected="0" subjects_at_risk="68"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="58"/>
                <counts group_id="E2" events="11" subjects_affected="8" subjects_at_risk="58"/>
                <counts group_id="E3" events="13" subjects_affected="12" subjects_at_risk="62"/>
                <counts group_id="E4" events="10" subjects_affected="10" subjects_at_risk="68"/>
                <counts group_id="E5" events="8" subjects_affected="8" subjects_at_risk="66"/>
                <counts group_id="E6" events="11" subjects_affected="11" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="58"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E4" events="6" subjects_affected="6" subjects_at_risk="68"/>
                <counts group_id="E5" events="3" subjects_affected="3" subjects_at_risk="66"/>
                <counts group_id="E6" events="6" subjects_affected="5" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="58"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="58"/>
                <counts group_id="E3" events="7" subjects_affected="6" subjects_at_risk="62"/>
                <counts group_id="E4" events="10" subjects_affected="10" subjects_at_risk="68"/>
                <counts group_id="E5" events="11" subjects_affected="10" subjects_at_risk="66"/>
                <counts group_id="E6" events="11" subjects_affected="9" subjects_at_risk="68"/>
              </event>
              <event>
                <sub_title>Maculo=papular rash</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="62"/>
                <counts group_id="E4" events="9" subjects_affected="8" subjects_at_risk="68"/>
                <counts group_id="E5" events="7" subjects_affected="6" subjects_at_risk="66"/>
                <counts group_id="E6" events="4" subjects_affected="4" subjects_at_risk="68"/>
              </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>Tara M. Brinkman, PhD</name_or_title>
      <organization>St. Jude Children's Research Hospital</organization>
      <phone>(901) 595-5683</phone>
      <email>tara.brinkman@stjude.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01700959
org study id: MIND
secondary id: P30CA021765
secondary id: NCI-2012-02053
nct id: NCT01700959
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Primary objective:

        1. To examine the efficacy of melatonin treatment on neurocognitive functioning in adult
           survivors of childhood cancer.

      Secondary objectives:

        1. To evaluate the efficacy of melatonin treatment on delayed sleep onset latency in
           long-term childhood cancer survivors.

        2. To investigate whether improvement in sleep onset latency due to melatonin treatment is
           associated with neurocognitive improvement in long-term childhood cancer survivors.

      This study is a randomized double-blind placebo controlled trial of time release melatonin
      for adult survivors of childhood cancer who demonstrate impaired neurocognitive functioning
      and/or difficulty falling asleep.
All participants undergo a general neurocognitive evaluation at baseline and 6-month
      follow-up, focused on assessment of intelligence, academic skills, attention, processing
      speed, memory and executive functions.

      Sleep parameters using self-report and actigraphy will be assessed at three time points
      during the study: Baseline, 3-months, and 6-months.

      Participants will be divided into 3 mutually exclusive groups:

        -  Cohort 1: Participant has neurocognitive impairment defined as performance on at least
           one measure of attention, memory, and/or executive functioning at or below the 10th
           percentile, AND is absent of delayed sleep onset latency defined as an inability to fall
           asleep within 30 minutes less than once a week during the past month.

        -  Cohort 2: Participant has neurocognitive impairment defined as performance on at least
           one measure of attention, memory, and/or executive functioning at or below the 10th
           percentile, AND has delayed sleep onset latency defined as self-report of an inability
           to fall asleep within 30 minutes at least once a week during the past month.

        -  Cohort 3: Participant is absent of neurocognitive impairment defined as performance
           >10th percentile on all six measures of attention, memory, and executive functioning,
           AND has delayed sleep onset latency defined as self-report of an inability to fall
           asleep within 30 minutes > once a week during the past month.

      Within each group, participants will be randomly assigned to take either 3 mgs of time
      release melatonin or placebo 1-2 hours before bedtime each night for 6 months.

      Psychosocial measures of health-related quality of life and psychological distress will be
      completed at baseline and following 6 months of melatonin/placebo treatment.

      Biological samples for serum melatonin levels will be collected at baseline and at the 6
      month follow-up evaluation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function.
time frame: Baseline and 6 months after start of therapy
description: Efficacy of melatonin treatment on neurocognitive functioning in adult survivors of childhood cancer (Cohorts 1 and 2 only). The measures were analyzed to compare change in neurocognitive performance from baseline to 6 months between active treatment and placebo groups. The unit of measure is a standardized z-score with a mean of 0 and standard deviation of 1. A higher z-score represents a better outcome.
measure: Sleep Onset Latency as Measured by Actigraphy and Self-report.
time frame: Baseline and six months after start of therapy
description: Efficacy of melatonin on delayed sleep onset latency in long-term childhood cancer survivors (Cohorts 2 and 3 only). The measures were analyzed to compare change in sleep onset latency from baseline to 6 months between active treatment and placebo groups.
measure: Neurocognitive Function as Measured by Performance on Standardized Tests of Attention, Memory, and Executive Function, and Sleep Onset Latency as Measured by Actigraphy and Self-report.
time frame: Baseline and six months after start of therapy
description: Investigate whether improvement in sleep onset latency due to melatonin treatment is associated with neurocognitive improvement in long-term childhood cancer survivors (Cohort 2). The change in neurocognitive performance from baseline to 6 months will be examined in relation to change in sleep onset latency. The unit of measure is a standardized z-score with a mean of 0 and standard deviation of 1. The unit of measurement is a correlation coefficient (Pearson's R2). The range is from -1.0 to 1.0. A zero indicates no correlation while values closer to -1.0 or 1.0 reflect a stronger association. A negative correlation suggests that as sleep latency decreased, neurocognitive functioning improved.
arm group label: Melatonin
arm group type: Active Comparator
description: Participants receive 3 mgs of time-release melatonin 1-2 hours prior to bedtime.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants receive a placebo identical to the time-release melatonin and are instructed to take it 1-2 hours prior to bedtime.
intervention type: Drug
intervention name: melatonin
description: Melatonin 3mg time release will be given. Participants will be instructed to take one 3mg time released tablet by mouth approximately 1-2 hours before initiating sleep onset, preferably at the same time each night.
arm group label: Melatonin
other name: N-Acetyl-5-Methoxytryptamine
intervention type: Drug
intervention name: placebo
description: Placebo tablets to match the melatonin will be comprised of inert substances.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tara Brinkman, PhD
role: Principal Investigator
affiliation: St. Jude Children's Research Hospital
facility: 
country: United States
url: http://www.stjude.org
description: St. Jude Children's Research Hospital
url: http://www.stjude.org/protocols
description: Clinical Trials Open at St. Jude
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Melatonin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 