<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/NCT03806296</url>
  </required_header>
  <id_info>
    <org_study_id>PRO18010292</org_study_id>
    <secondary_id>R01DA044143</secondary_id>
    <nct_id>NCT03806296</nct_id>
  </id_info>
  <brief_title>Delayed Sleep Timing in Teens Study</brief_title>
  <official_title>Delayed Sleep Phase and Risk for Adolescent Substance Use</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This study will (1) comprehensively characterize the substance use disorder (SUD) risk&#xD;
      profile associated with adolescent Delayed Sleep Phase (DSP), and (2) probe whether SUD risk&#xD;
      is diminished by altering sleep/circadian timing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Mounting evidence indicates that delayed sleep phase (DSP) may confer risk for adolescent&#xD;
      substance use (SU) and SUDs. However, the exact nature of this link and the mechanisms&#xD;
      underlying it remain unclear. Circadian misalignment, a mismatch between late sleep hours and&#xD;
      early school start times, is a compelling potential contributor to elevated SU in adolescent&#xD;
      DSP with plausible neurobehavioral mechanisms. The investigators hypothesize that&#xD;
      DSP-associated circadian misalignment decreases impulse control and increases reward&#xD;
      sensitivity, thereby increasing SUD risk.&#xD;
&#xD;
      This study will, for the first time, (1) comprehensively characterize the SUD risk profile&#xD;
      associated with adolescent DSP, and (2) probe whether SUD risk is diminished by altering&#xD;
      sleep/circadian timing. The study will assess both established markers of SUD risk and&#xD;
      putative neurobehavioral mechanisms (impulsivity and reward sensitivity). Specifically, the&#xD;
      investigators will employ a comprehensive, multi-method approach to examining DSP's role in&#xD;
      SUD risk, combining laboratory, experimental, and longitudinal studies. The investigators&#xD;
      will recruit a sample of 150 eleventh and twelfth graders (16-19 y/o), divided between 100&#xD;
      DSP and 50 normal phase teens. The investigators will focus on cannabis and alcohol use given&#xD;
      their prevalent use in adolescents and evident links to DSP.&#xD;
&#xD;
      In the experimental study, the investigators will probe whether stabilizing circadian phase&#xD;
      in the DSP group (n=100) by using sleep scheduling and chronotherapeutic approaches (i.e.,&#xD;
      dim light in the evening and bright light in the morning) improves sleep and neurobehavioral&#xD;
      function relevant to SUD risk.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 3, 2018</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 30, 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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Circadian alignment</measure>
    <time_frame>Post-manipulation (comparing assessment after ~2-week sleep manipulation to the assessment at baseline)</time_frame>
    <description>Interval between dim light melatonin onset and midsleep</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Behavioral inhibition</measure>
    <time_frame>Post-manipulation (comparing assessment after ~2-week sleep manipulation to the assessment at baseline)</time_frame>
    <description>Accuracy on Cued Go/No-Go Task, specifically correct response (withholding response) on go trials with no/go target</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Reward motivation (behavioral)</measure>
    <time_frame>Post-manipulation (comparing assessment after ~2-week sleep manipulation to the assessment at baseline)</time_frame>
    <description>Adjusted average pumps on Balloon Analogue Risk Task, a computerized measure of risk taking behavior in participants are presented with a series of balloons and offered the chance to earn money by pumping each balloon up by clicking a button.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neural correlates of impulse control</measure>
    <time_frame>Post-manipulation (comparing assessment after ~2-week sleep manipulation to the assessment at baseline)</time_frame>
    <description>Activation within the Executive Control Network during the Stop Signal Task. Specifically, activation is defined as bold signal in regions of the Executive Control Network (particularly the inferior frontal gyrus) on correct Stop trials versus correct Go trials.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neural correlates of reward anticipation</measure>
    <time_frame>Post-manipulation (comparing assessment after ~2-week sleep manipulation to the assessment at baseline)</time_frame>
    <description>Activation within the reward network during the Monetary Incentive Delay task. Specifically, activation is defined as bold signals in regions of the reward network (particularly the ventral striatum) on reward anticipation trials versus no money trials.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cannabis use</measure>
    <time_frame>During follow-ups after the manipulation through study completion, up to 5 years</time_frame>
    <description>Cannabis use on Time Line Follow Back interview. Specifically, the frequency (# of days) of cannabis use (yes/no) in the past 2 months.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Delayed Sleep Phase</condition>
  <arm_group>
    <arm_group_label>Manipulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For ~2 weeks, participants will be asked to adhere to the following:&#xD;
Sleep scheduling--advance bedtime by 1.5 hours ( + sleep duration)&#xD;
Decrease evening blue light exposure via blue blocker goggles (2 h before bed)&#xD;
Increase morning bright light exposure via bright light goggles (30 m after rise)&#xD;
Monitor sleep, mood, and substance use via smartphone-based platform and wrist actigraph</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>For ~2 weeks, participants will asked to adhere to the following:&#xD;
- Monitor sleep, mood, and substance use via smartphone-based platform and wrist actigraph</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Increase morning bright light</intervention_name>
    <description>Participants will wear Re-Timer bright glasses for 30 minutes each morning</description>
    <arm_group_label>Manipulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Decrease evening blue light</intervention_name>
    <description>Participants will wear tinted glasses that block blue wavelength light for 2 hours before bed</description>
    <arm_group_label>Manipulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Sleep scheduling</intervention_name>
    <description>Participants will advance their weekday bedtime and maintain their weekday risetime on weekends</description>
    <arm_group_label>Manipulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Monitor sleep, mood, and substance use</intervention_name>
    <description>Participants will monitor sleep, mood, and substance use via smartphone-based platform and wrist actigraphy</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Manipulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 16-19 years&#xD;
&#xD;
          -  Currently in 11th or 12th grade and enrolled in a traditional high-school; or cyber&#xD;
             school with synchronous classes (not home-schooled)&#xD;
&#xD;
          -  Physically and psychiatrically healthy, as determined by instruments described below&#xD;
&#xD;
          -  Provision of written informed consent and assent&#xD;
&#xD;
        Additional inclusion criterion for Experimental protocol&#xD;
&#xD;
          -  Meets operational definition of delayed sleep phase (DSP; weekend bedtime ≥1 AM)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant or unstable acute or chronic medical conditions&#xD;
&#xD;
          -  Past or current bipolar disorder or psychotic disorder&#xD;
&#xD;
          -  Past or current substance use disorder other than alcohol use disorder or cannabis use&#xD;
             disorder&#xD;
&#xD;
          -  Past month recreational drug use other than alcohol, cannabis, and nicotine&#xD;
&#xD;
          -  Current syndromal sleep disorders other than insomnia and delayed sleep phase disorder&#xD;
&#xD;
          -  Medications that interfere with sleep and/or reward function (antidepressants, and&#xD;
             stimulants prescribed for ADHD are permitted)&#xD;
&#xD;
          -  Conditions that would interfere with the MRI procedures (e.g., non-removal&#xD;
             ferromagnetic devices)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>19 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Brant P Hasler, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kathryn Guo</last_name>
    <phone>412-246-6422</phone>
    <email>guok@upmc.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Western Psychiatric Institute and Clinic</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kathryn Guo</last_name>
      <phone>412-246-6422</phone>
      <email>guok@upmc.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>July 5, 2023</last_update_submitted>
  <last_update_submitted_qc>July 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Brant Hasler</investigator_full_name>
    <investigator_title>Assistant Professor of Psychiatry, Psychology, and Clinical and Translational Science</investigator_title>
  </responsible_party>
  <keyword>sleep</keyword>
  <keyword>circadian</keyword>
  <keyword>adolescence</keyword>
  <keyword>substance use</keyword>
  <keyword>reward</keyword>
  <keyword>impulse control</keyword>
  <!-- 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/NCT03806296
org study id: PRO18010292
secondary id: R01DA044143
nct id: NCT03806296
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study will (1) comprehensively characterize the substance use disorder (SUD) risk
      profile associated with adolescent Delayed Sleep Phase (DSP), and (2) probe whether SUD risk
      is diminished by altering sleep/circadian timing.
Mounting evidence indicates that delayed sleep phase (DSP) may confer risk for adolescent
      substance use (SU) and SUDs. However, the exact nature of this link and the mechanisms
      underlying it remain unclear. Circadian misalignment, a mismatch between late sleep hours and
      early school start times, is a compelling potential contributor to elevated SU in adolescent
      DSP with plausible neurobehavioral mechanisms. The investigators hypothesize that
      DSP-associated circadian misalignment decreases impulse control and increases reward
      sensitivity, thereby increasing SUD risk.

      This study will, for the first time, (1) comprehensively characterize the SUD risk profile
      associated with adolescent DSP, and (2) probe whether SUD risk is diminished by altering
      sleep/circadian timing. The study will assess both established markers of SUD risk and
      putative neurobehavioral mechanisms (impulsivity and reward sensitivity). Specifically, the
      investigators will employ a comprehensive, multi-method approach to examining DSP's role in
      SUD risk, combining laboratory, experimental, and longitudinal studies. The investigators
      will recruit a sample of 150 eleventh and twelfth graders (16-19 y/o), divided between 100
      DSP and 50 normal phase teens. The investigators will focus on cannabis and alcohol use given
      their prevalent use in adolescents and evident links to DSP.

      In the experimental study, the investigators will probe whether stabilizing circadian phase
      in the DSP group (n=100) by using sleep scheduling and chronotherapeutic approaches (i.e.,
      dim light in the evening and bright light in the morning) improves sleep and neurobehavioral
      function relevant to SUD risk.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Circadian alignment
time frame: Post-manipulation (comparing assessment after ~2-week sleep manipulation to the assessment at baseline)
description: Interval between dim light melatonin onset and midsleep
measure: Behavioral inhibition
time frame: Post-manipulation (comparing assessment after ~2-week sleep manipulation to the assessment at baseline)
description: Accuracy on Cued Go/No-Go Task, specifically correct response (withholding response) on go trials with no/go target
measure: Reward motivation (behavioral)
time frame: Post-manipulation (comparing assessment after ~2-week sleep manipulation to the assessment at baseline)
description: Adjusted average pumps on Balloon Analogue Risk Task, a computerized measure of risk taking behavior in participants are presented with a series of balloons and offered the chance to earn money by pumping each balloon up by clicking a button.
measure: Neural correlates of impulse control
time frame: Post-manipulation (comparing assessment after ~2-week sleep manipulation to the assessment at baseline)
description: Activation within the Executive Control Network during the Stop Signal Task. Specifically, activation is defined as bold signal in regions of the Executive Control Network (particularly the inferior frontal gyrus) on correct Stop trials versus correct Go trials.
measure: Neural correlates of reward anticipation
time frame: Post-manipulation (comparing assessment after ~2-week sleep manipulation to the assessment at baseline)
description: Activation within the reward network during the Monetary Incentive Delay task. Specifically, activation is defined as bold signals in regions of the reward network (particularly the ventral striatum) on reward anticipation trials versus no money trials.
measure: Cannabis use
time frame: During follow-ups after the manipulation through study completion, up to 5 years
description: Cannabis use on Time Line Follow Back interview. Specifically, the frequency (# of days) of cannabis use (yes/no) in the past 2 months.
arm group label: Manipulation
arm group type: Experimental
description: For ~2 weeks, participants will be asked to adhere to the following:
Sleep scheduling--advance bedtime by 1.5 hours ( + sleep duration)
Decrease evening blue light exposure via blue blocker goggles (2 h before bed)
Increase morning bright light exposure via bright light goggles (30 m after rise)
Monitor sleep, mood, and substance use via smartphone-based platform and wrist actigraph
arm group label: Control
arm group type: Active Comparator
description: For ~2 weeks, participants will asked to adhere to the following:
- Monitor sleep, mood, and substance use via smartphone-based platform and wrist actigraph
intervention type: Other
intervention name: Increase morning bright light
description: Participants will wear Re-Timer bright glasses for 30 minutes each morning
arm group label: Manipulation
intervention type: Other
intervention name: Decrease evening blue light
description: Participants will wear tinted glasses that block blue wavelength light for 2 hours before bed
arm group label: Manipulation
intervention type: Behavioral
intervention name: Sleep scheduling
description: Participants will advance their weekday bedtime and maintain their weekday risetime on weekends
arm group label: Manipulation
intervention type: Behavioral
intervention name: Monitor sleep, mood, and substance use
description: Participants will monitor sleep, mood, and substance use via smartphone-based platform and wrist actigraphy
arm group label: Control
arm group label: Manipulation
criteria: 
gender: All
minimum age: 16 Years
maximum age: 19 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Brant P Hasler, PhD
role: Principal Investigator
affiliation: University of Pittsburgh
last name: Kathryn Guo
phone: 412-246-6422
email: guok@upmc.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Brant Hasler
investigator title: Assistant Professor of Psychiatry, Psychology, and Clinical and Translational Science