<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/NCT03826563</url>
  </required_header>
  <id_info>
    <org_study_id>18-014932</org_study_id>
    <nct_id>NCT03826563</nct_id>
  </id_info>
  <brief_title>Melatonin Effects on Sleep and Circadian Rhythm in Youth and Young Adults With At-risk Symptoms</brief_title>
  <official_title>Melatonin Effects on Sleep and Circadian Rhythm in Youth and Young Adults With At-risk Symptoms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Brain and Behavior Research Foundation (NARSAD Young Investigator Award, Grant Number 26742)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Hospital of Philadelphia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Randomized control trial assessing supplemental melatonin for youth with at-risk or psychotic&#xD;
      symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Context: Sleep disturbances and circadian dysrhythmias have been associated with psychotic&#xD;
      symptom severity in Psychosis Spectrum (PS) youths. Supplemental melatonin is a safe&#xD;
      over-the-counter dietary supplement, and several studies have found that melatonin improves&#xD;
      sleep across several childhood neuropsychiatric disorders.&#xD;
&#xD;
      Objectives: Investigators seeks to determine whether supplemental melatonin improves sleep&#xD;
      and circadian alignment in PS youth. Investigators will also investigate whether supplemental&#xD;
      melatonin affects psychotic symptoms, neurocognition, and peripheral inflammatory and&#xD;
      oxidative stress markers.&#xD;
&#xD;
      Study Design: Parallel group, double-blind, randomized, placebo-controlled trial&#xD;
      Setting/Participants: 40 PS youths ages 11-30 years old (throughout the protocol we use&#xD;
      &quot;youth&quot; to describe this age group) with sleep disturbances will be recruited from an extant&#xD;
      cohort of PS youths followed by our lab in the Philadelphia Neurodevelopmental Cohort (PNC),&#xD;
      Children's Hospital of Philadelphia (CHOP), University of Pennsylvania (UPenn), and the&#xD;
      surrounding community. The study will be conducted at CHOP and UPenn.&#xD;
&#xD;
      Study Interventions and Measures: Youths will be randomized to receive pill placebo or oral&#xD;
      melatonin. Participants will take melatonin (or placebo) at the same time every evening for 2&#xD;
      weeks (final dose range 2.5-10 mg nightly). Outcomes will be assessed at 1 week, 2 weeks, and&#xD;
      6-months. Primary outcomes will be changes in self-reported sleep and actigraph-measured&#xD;
      sleep and circadian rhythm. Secondary outcomes will be psychotic symptoms, neurocognition,&#xD;
      and peripheral blood markers of inflammation and oxidative stress.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 18, 2019</start_date>
  <completion_date type="Actual">April 7, 2023</completion_date>
  <primary_completion_date type="Actual">April 7, 2023</primary_completion_date>
  <phase>N/A</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>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Only the pharmacy will know the randomization arms.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Actigraph-measured sleep (increased total sleep time)</measure>
    <time_frame>Change in total sleep time from melatonin randomization day (Day 0) to Day 14</time_frame>
    <description>Actigraph-measured total sleep time will be used to assess actigraph-measured sleep efficacy, Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improved self-reported sleep</measure>
    <time_frame>Change in total PSQI from melatonin randomization day (Day 0) to Day 14</time_frame>
    <description>Pittsburgh Sleep Quality Index (PSQI); range is 0-21, with higher scores indicating poorer sleep</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Decreased actigraph-measured sleep latency</measure>
    <time_frame>Change in actigraph-measured sleep onset latency from melatonin randomization day (Day 0) to Day 14</time_frame>
    <description>How long it takes a participant to fall asleep; Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software. Sleep latency is an Actilife software outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Increased actigraph-measured sleep efficiency</measure>
    <time_frame>Change from Randomization day (Day 0) to Day 14.</time_frame>
    <description>Amount of time participant spends sleeping divided by the amount of time the patient spends in bed. Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software. Sleep efficiency is an Actilife software outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Lower autocorrelation function</measure>
    <time_frame>Change in actigraph-measured autocorrelation from melatonin randomization day (Day 0) to Day 14</time_frame>
    <description>Ac is the slope of the time correlation line (log-trans- formed); indicative of rhythm fragmentation; lower values represent less fragmented rhythms. Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software. Autocorrelation function is an Actilife software outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Increased activity (M10)</measure>
    <time_frame>Change in actigraph-measured M10 from melatonin randomization day (Day 0) to Day 14</time_frame>
    <description>mean activity level during the most active 10 h of the day; higher values are indicative of a more active lifestyle. M10 is an Actilife software output.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Psychosis</condition>
  <condition>Sleep</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will receive pill placebo nightly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Melatonin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive oral melatonin tablets 2.5-10mg nightly for 2 weeks. All will receive melatonin 5mg for one week, then at the 1 week visit, the dose can be continued at 5mg or adjusted to 2.5mg or 10mg nightly based on clinical assessment of patient response and side effects.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>oral melatonin tablets (NatureMade brand)</intervention_name>
    <description>melatonin tablets</description>
    <arm_group_label>Melatonin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>pill placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males or females age 11-30 years old and patient at the Children's Hospital of&#xD;
             Philadelphia (CHOP), University of Pennsylvania (UPenn), or member of the surrounding&#xD;
             community&#xD;
&#xD;
          -  Subthreshold psychosis-risk positive symptoms (e.g. hallucinations or unusual beliefs)&#xD;
             on the Structured Interview of Psychosis-Risk Syndromes (SIPS)&#xD;
&#xD;
          -  At least mild sleep disturbances on the SIPS (&gt;=1 on the SIPS sleep item (G1)) with&#xD;
             difficulties with&#xD;
&#xD;
          -  Must have difficulties with sleep onset, sleep awakenings, or maintaining a regular&#xD;
             sleep schedule.&#xD;
&#xD;
          -  Willingness to report all changes in medications and therapy during the study&#xD;
&#xD;
          -  Intelligence Quotient (IQ) &gt; 70&#xD;
&#xD;
          -  If female, not breastfeeding and not pregnant and willing to use effective birth&#xD;
             control for the duration of the study (e.g. abstinence or oral contraception).&#xD;
&#xD;
          -  Medically healthy&#xD;
&#xD;
          -  Fluent in English&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Psychiatric symptoms with imminent safety concern (e.g. intractable and escalating&#xD;
             suicidal ideation)&#xD;
&#xD;
          -  Currently taking melatonin, having taken melatonin daily within the 2 weeks prior to&#xD;
             Visit 1, or having a history of an intolerance or allergy to melatonin.&#xD;
&#xD;
          -  Medication or treatment changes in the 4 weeks prior to Visit 1 .&#xD;
&#xD;
          -  Anticipated medication or other treatment (e.g. type of psychotherapy) changes in the&#xD;
             three weeks after study enrollment.&#xD;
&#xD;
          -  IQ &lt;70&#xD;
&#xD;
          -  Taking any medication whose potential interactions with melatonin present a&#xD;
             significant risk or limit the effect of melatonin in the judgment of the&#xD;
             investigators.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>11 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raquel Gur, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Philadelphia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>May 5, 2023</last_update_submitted>
  <last_update_submitted_qc>May 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psychotic Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melatonin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>We will share data within the CHOP research group.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03826563
org study id: 18-014932
nct id: NCT03826563
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Randomized control trial assessing supplemental melatonin for youth with at-risk or psychotic
      symptoms.
Context: Sleep disturbances and circadian dysrhythmias have been associated with psychotic
      symptom severity in Psychosis Spectrum (PS) youths. Supplemental melatonin is a safe
      over-the-counter dietary supplement, and several studies have found that melatonin improves
      sleep across several childhood neuropsychiatric disorders.

      Objectives: Investigators seeks to determine whether supplemental melatonin improves sleep
      and circadian alignment in PS youth. Investigators will also investigate whether supplemental
      melatonin affects psychotic symptoms, neurocognition, and peripheral inflammatory and
      oxidative stress markers.

      Study Design: Parallel group, double-blind, randomized, placebo-controlled trial
      Setting/Participants: 40 PS youths ages 11-30 years old (throughout the protocol we use
      "youth" to describe this age group) with sleep disturbances will be recruited from an extant
      cohort of PS youths followed by our lab in the Philadelphia Neurodevelopmental Cohort (PNC),
      Children's Hospital of Philadelphia (CHOP), University of Pennsylvania (UPenn), and the
      surrounding community. The study will be conducted at CHOP and UPenn.

      Study Interventions and Measures: Youths will be randomized to receive pill placebo or oral
      melatonin. Participants will take melatonin (or placebo) at the same time every evening for 2
      weeks (final dose range 2.5-10 mg nightly). Outcomes will be assessed at 1 week, 2 weeks, and
      6-months. Primary outcomes will be changes in self-reported sleep and actigraph-measured
      sleep and circadian rhythm. Secondary outcomes will be psychotic symptoms, neurocognition,
      and peripheral blood markers of inflammation and oxidative stress.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Only the pharmacy will know the randomization arms.
measure: Actigraph-measured sleep (increased total sleep time)
time frame: Change in total sleep time from melatonin randomization day (Day 0) to Day 14
description: Actigraph-measured total sleep time will be used to assess actigraph-measured sleep efficacy, Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software.
measure: Improved self-reported sleep
time frame: Change in total PSQI from melatonin randomization day (Day 0) to Day 14
description: Pittsburgh Sleep Quality Index (PSQI); range is 0-21, with higher scores indicating poorer sleep
measure: Decreased actigraph-measured sleep latency
time frame: Change in actigraph-measured sleep onset latency from melatonin randomization day (Day 0) to Day 14
description: How long it takes a participant to fall asleep; Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software. Sleep latency is an Actilife software outcome.
measure: Increased actigraph-measured sleep efficiency
time frame: Change from Randomization day (Day 0) to Day 14.
description: Amount of time participant spends sleeping divided by the amount of time the patient spends in bed. Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software. Sleep efficiency is an Actilife software outcome.
measure: Lower autocorrelation function
time frame: Change in actigraph-measured autocorrelation from melatonin randomization day (Day 0) to Day 14
description: Ac is the slope of the time correlation line (log-trans- formed); indicative of rhythm fragmentation; lower values represent less fragmented rhythms. Actigraphs from the Actigraph Company will be used to analyze the data using Actilife software. Autocorrelation function is an Actilife software outcome.
measure: Increased activity (M10)
time frame: Change in actigraph-measured M10 from melatonin randomization day (Day 0) to Day 14
description: mean activity level during the most active 10 h of the day; higher values are indicative of a more active lifestyle. M10 is an Actilife software output.
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects will receive pill placebo nightly
arm group label: Melatonin
arm group type: Experimental
description: Subjects will receive oral melatonin tablets 2.5-10mg nightly for 2 weeks. All will receive melatonin 5mg for one week, then at the 1 week visit, the dose can be continued at 5mg or adjusted to 2.5mg or 10mg nightly based on clinical assessment of patient response and side effects.
intervention type: Drug
intervention name: oral melatonin tablets (NatureMade brand)
description: melatonin tablets
arm group label: Melatonin
intervention type: Other
intervention name: Placebo
description: pill placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 11 Years
maximum age: 30 Years
healthy volunteers: No
last name: Raquel Gur, MD
role: Principal Investigator
affiliation: Children's Hospital of Philadelphia
facility: 
country: United States
responsible party type: Sponsor
mesh term: Psychotic Disorders
mesh term: Melatonin
sharing ipd: No
ipd description: We will share data within the CHOP research group.