xml: <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/NCT06041048</url>
    </required_header>
    <id_info>
      <org_study_id>1939774</org_study_id>
      <nct_id>NCT06041048</nct_id>
    </id_info>
    <brief_title>Investigation of Locus Coeruleus Function in Sustained Attention</brief_title>
    <acronym>LC</acronym>
    <official_title>Investigation of Locus Coeruleus Function in Sustained Attention</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of California, Davis</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of California, Davis</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The norepinephrine-producing locus coeruleus (LC) is thought to be central to a wide array of&#xD;
        cognitive functions, like attention and goal pursuit, and has been implicated in dysfunctions&#xD;
        including attention deficit hyperactivity disorder and schizophrenia. The goal of this&#xD;
        proposal is to develop methods that permit measurement of activity in the human LC. Because&#xD;
        the LC is small and located in the pons, the Investigators will use high resolution magnetic&#xD;
        resonance imaging techniques tailored to the brainstem environment, including&#xD;
        neuromelanin-sensitive images shown to delineate the LC, combined with pharmacological&#xD;
        manipulation to confirm the location of functional activity.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Attention failures negatively impact goal pursuit and have significant consequences on&#xD;
        performance in many environments. Attentional control of perceptual, motor and cognitive&#xD;
        functions are believed to be partly determined by functioning of the locus&#xD;
        coeruleus-norepinephrine (LC-NE) system. The LC, a small brainstem nucleus that is the&#xD;
        primary source for NE in the forebrain, has motivated hypotheses about human cognition,&#xD;
        including mental health disorders with known alterations in attention and cognition (e.g.,&#xD;
        attentiondeficit/ hyperactivity disorder (ADHD), schizophrenia) even though methods for&#xD;
        measuring human LC activity have significant limitations. Existing methods to study LC&#xD;
        function in humans rely on pupillometry and fMRI.&#xD;
  &#xD;
        Because pupil diameter correlates with LC activity, it has been used as a proxy for LC&#xD;
        activity. However, the anatomical pathway linking the LC to pupil dilation has not been&#xD;
        established and pupil diameter also correlates with activity in other brain areas. Thus,&#xD;
        inferring LC activity from pupillometry alone is problematic. fMRI has also been used to&#xD;
        measure activity from the LC, but the imaging methods used to date have relied on resolutions&#xD;
        that are coarse relative to the size and shape of LC. Prior fMRI results have therefore not&#xD;
        been adequate for event-related analyses. The goal of the proposed work is to develop and&#xD;
        validate methods for using fMRI to measure LC activity, specifically event-related responses&#xD;
        that will allow for testing of influential hypotheses of LC function in humans. This goal is&#xD;
        appropriate for the R21 mechanism, which is meant to &quot;encourage exploratory/developmental&#xD;
        research by providing support for the early and conceptual stages of project development&quot; and&#xD;
        to test innovative, high-risk, high reward research. This project has two specific aims,&#xD;
        which are both tested with sustained attention tasks. The first aim uses high-resolution fMRI&#xD;
        to maximize the number of measurements within LC combined with neuromelanin-sensitive imaging&#xD;
        to localize BOLD responses to LC. The Investigators will measure (a) pre-trial activity&#xD;
        (i.e., during inter-trial intervals; this period is thought to reflect tonic LC activity) and&#xD;
        (b) trial response (i.e., phasic LC activity) by estimating the beta weights for each trial.&#xD;
        The second aim uses modafinil administration to modulate LC activity and confirm the location&#xD;
        of BOLD responses measured during the sustained attention tasks to the LC. The Investigators&#xD;
        will administer modafinil and placebo to participants in a double-blind, placebo-controlled&#xD;
        crossover study. Pupillometry data will also be collected for both the modafinil and placebo&#xD;
        conditions, and the Investigators will use the pupillometry data to test for a correlation&#xD;
        with LC BOLD response amplitude. This combination of techniques will demonstrate whether fMRI&#xD;
        can be used to measure LC activity in a targeted fashion. Developing these tools meets Goal 1&#xD;
        (Strategy 1.3D) of the 2020 Strategic Plan of the NIMH by permitting direct measurement of a&#xD;
        brain structure central in attentional control.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">August 2024</completion_date>
    <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Brain activity - BOLD response</measure>
      <time_frame>1 hour</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Attention on Oddball and POP task</measure>
      <time_frame>1 hour</time_frame>
      <description>Response time and accuracy on Oddball and POP task</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Attention - no Condition is Being Assessed - Healthy Adults</condition>
    <arm_group>
      <arm_group_label>Modafinil</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Single oral dose (200 mg) of medication versus placebo given to healthy control subjects</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Oral placebo</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Modafinil</intervention_name>
      <description>Single dose (200 mg) of medication versus placebo given to healthy control subjects</description>
      <arm_group_label>Modafinil</arm_group_label>
      <arm_group_label>Placebo</arm_group_label>
      <other_name>Provigil</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Between the ages of 18 - 60 years of age,&#xD;
  &#xD;
            -  Typically developing, healthy adult&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of schizophrenia, other forms of psychosis,&#xD;
  &#xD;
            -  Specific or focal neurological disorder or severe alcohol or drug use disorder within&#xD;
               the past 5 years&#xD;
  &#xD;
            -  History of left ventricular hypertrophy or in patients with mitral valve prolapse who&#xD;
               have experienced the mitral valve prolapse syndrome when previously receiving CNS&#xD;
               stimulants, or who have had recent history of myocardial infarction or unstable&#xD;
               angina.&#xD;
  &#xD;
            -  Volunteers with known hypersensitivity to modafinil or armodafinil or its inactive&#xD;
               ingredients&#xD;
  &#xD;
            -  Known allergy/sensitivity or any hypersensitivity to components of modafinil or its&#xD;
               formulation&#xD;
  &#xD;
            -  Inability to swallow tablets or tolerate oral medication;&#xD;
  &#xD;
            -  Pregnant or nursing (participants will be required to have a negative pregnancy test)&#xD;
  &#xD;
            -  Contraindication for MRI scanning (metal implants, pacemakers, metal foreign bodies,&#xD;
               or pregnancy)&#xD;
  &#xD;
            -  Use of psychotropic medication within the past week&#xD;
  &#xD;
            -  Claustrophobic and not comfortable being in a small space may also not want to&#xD;
               participate&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Julie Schweitzer</last_name>
      <phone>9164941892</phone>
      <email>jschweitzer@ucdavis.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Prerona Mukhejee</last_name>
      <phone>4155353954</phone>
      <email>pmukherjee@ucdavis.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of California, Davis</name>
        <address>
          <city>Sacramento</city>
          <state>California</state>
          <zip>95817</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Ian Farnsworth</last_name>
        <email>ijfarnsworth@ucdavis.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 17, 2023</study_first_submitted>
    <study_first_submitted_qc>September 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 10, 2023</last_update_submitted>
    <last_update_submitted_qc>September 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of California, Davis</investigator_affiliation>
      <investigator_full_name>Julie Schweitzer, PhD</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Modafinil</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>De-identified data will be uploaded to the NIH NDA, following their procedures.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_time_frame>Within two years after data are analyzed by the investigative team. How long it will be available is determined by the NIH.</ipd_time_frame>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06041048
  org study id: 1939774
  nct id: NCT06041048
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  The norepinephrine-producing locus coeruleus (LC) is thought to be central to a wide array of
        cognitive functions, like attention and goal pursuit, and has been implicated in dysfunctions
        including attention deficit hyperactivity disorder and schizophrenia. The goal of this
        proposal is to develop methods that permit measurement of activity in the human LC. Because
        the LC is small and located in the pons, the Investigators will use high resolution magnetic
        resonance imaging techniques tailored to the brainstem environment, including
        neuromelanin-sensitive images shown to delineate the LC, combined with pharmacological
        manipulation to confirm the location of functional activity.
  Attention failures negatively impact goal pursuit and have significant consequences on
        performance in many environments. Attentional control of perceptual, motor and cognitive
        functions are believed to be partly determined by functioning of the locus
        coeruleus-norepinephrine (LC-NE) system. The LC, a small brainstem nucleus that is the
        primary source for NE in the forebrain, has motivated hypotheses about human cognition,
        including mental health disorders with known alterations in attention and cognition (e.g.,
        attentiondeficit/ hyperactivity disorder (ADHD), schizophrenia) even though methods for
        measuring human LC activity have significant limitations. Existing methods to study LC
        function in humans rely on pupillometry and fMRI.
  
        Because pupil diameter correlates with LC activity, it has been used as a proxy for LC
        activity. However, the anatomical pathway linking the LC to pupil dilation has not been
        established and pupil diameter also correlates with activity in other brain areas. Thus,
        inferring LC activity from pupillometry alone is problematic. fMRI has also been used to
        measure activity from the LC, but the imaging methods used to date have relied on resolutions
        that are coarse relative to the size and shape of LC. Prior fMRI results have therefore not
        been adequate for event-related analyses. The goal of the proposed work is to develop and
        validate methods for using fMRI to measure LC activity, specifically event-related responses
        that will allow for testing of influential hypotheses of LC function in humans. This goal is
        appropriate for the R21 mechanism, which is meant to "encourage exploratory/developmental
        research by providing support for the early and conceptual stages of project development" and
        to test innovative, high-risk, high reward research. This project has two specific aims,
        which are both tested with sustained attention tasks. The first aim uses high-resolution fMRI
        to maximize the number of measurements within LC combined with neuromelanin-sensitive imaging
        to localize BOLD responses to LC. The Investigators will measure (a) pre-trial activity
        (i.e., during inter-trial intervals; this period is thought to reflect tonic LC activity) and
        (b) trial response (i.e., phasic LC activity) by estimating the beta weights for each trial.
        The second aim uses modafinil administration to modulate LC activity and confirm the location
        of BOLD responses measured during the sustained attention tasks to the LC. The Investigators
        will administer modafinil and placebo to participants in a double-blind, placebo-controlled
        crossover study. Pupillometry data will also be collected for both the modafinil and placebo
        conditions, and the Investigators will use the pupillometry data to test for a correlation
        with LC BOLD response amplitude. This combination of techniques will demonstrate whether fMRI
        can be used to measure LC activity in a targeted fashion. Developing these tools meets Goal 1
        (Strategy 1.3D) of the 2020 Strategic Plan of the NIMH by permitting direct measurement of a
        brain structure central in attentional control.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Basic Science
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Brain activity - BOLD response
  time frame: 1 hour
  measure: Attention on Oddball and POP task
  time frame: 1 hour
  description: Response time and accuracy on Oddball and POP task
  arm group label: Modafinil
  arm group type: Active Comparator
  description: Single oral dose (200 mg) of medication versus placebo given to healthy control subjects
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Oral placebo
  intervention type: Drug
  intervention name: Modafinil
  description: Single dose (200 mg) of medication versus placebo given to healthy control subjects
  arm group label: Modafinil
  arm group label: Placebo
  other name: Provigil
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Julie Schweitzer
  phone: 9164941892
  email: jschweitzer@ucdavis.edu
  last name: Prerona Mukhejee
  phone: 4155353954
  email: pmukherjee@ucdavis.edu
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: University of California, Davis
  investigator full name: Julie Schweitzer, PhD
  investigator title: Professor
  mesh term: Modafinil
  sharing ipd: Yes
  ipd description: De-identified data will be uploaded to the NIH NDA, following their procedures.
  ipd info type: Study Protocol
  ipd time frame: Within two years after data are analyzed by the investigative team. How long it will be available is determined by the NIH.