<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/NCT02260570</url>
  </required_header>
  <id_info>
    <org_study_id>D0825-I</org_study_id>
    <secondary_id>1I01RX000825-01</secondary_id>
    <nct_id>NCT02260570</nct_id>
  </id_info>
  <brief_title>Remediation of Impaired Self-Regulation in Patients With Mild TBI</brief_title>
  <official_title>Remediation of Impaired Self-Regulation in Patients With Mild TBI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, Berkeley</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>VA Office of Research and Development</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The ability to regulate impulses enables us to plan for the future, to maintain focus in the&#xD;
      face of distractions (i.e. to encode memories), and to manage emotions. This self regulation&#xD;
      can be compromised in individuals who have a history of mild traumatic brain injury and&#xD;
      co-occurring disorders. In this study the investigators are using functional MRI scanning to&#xD;
      understand how memory and self regulation are expressed in the brains of people with a&#xD;
      history of mild traumatic brain injury. The investigators are also testing whether the&#xD;
      medication tolcapone may improve memory and self regulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this randomized, double-blind, placebo-controlled, crossover cognitive neuroscience study,&#xD;
      the investigators are evaluating whether the COMT inhibitor tolcapone impacts memory and self&#xD;
      regulation, as measured both behaviorally (via cognitive testing) and neurophysiologically&#xD;
      (via functional MRI). A new study arm that does not include use of tolcapone, nominally&#xD;
      equivalent to the placebo arm only, is now also included to address performance on cognitive&#xD;
      testing alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2015</start_date>
  <completion_date type="Actual">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">June 30, 2021</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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Blood Oxygen Level Dependent (BOLD) brain signal measured using functional MRI</measure>
    <time_frame>Approximately 60-240 minutes following tolcapone/placebo administration</time_frame>
    <description>BOLD signal provides an indirect measure of brain activity during cognitive testing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Performance on Cognitive Testing</measure>
    <time_frame>Approximately 60-240 minutes following tolcapone/placebo administration</time_frame>
    <description>Tasks to assess cognition will be performed while subjects are in the MRI scanner</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Mild Traumatic Brain Injury</condition>
  <arm_group>
    <arm_group_label>Functional MRI Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This cognitive science study consists of a single &quot;arm&quot; in which all subjects receive both tolcapone and placebo in randomized, double-blind, counterbalanced, crossover fashion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tolcapone</intervention_name>
    <description>COMT Inhibitor</description>
    <arm_group_label>Functional MRI Arm</arm_group_label>
    <other_name>Tasmar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A pill that contains no active ingredient</description>
    <arm_group_label>Functional MRI Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Veteran ages 18-50 and in general good health;&#xD;
&#xD;
          -  Able to read English at a 6th grade level;&#xD;
&#xD;
          -  Able to provide written informed consent;&#xD;
&#xD;
          -  Normal or corrected to normal visual acuity;&#xD;
&#xD;
          -  Stable doses of all medications (2 weeks or greater);&#xD;
&#xD;
          -  History of mild traumatic brain injury greater than 6 months prior to participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications to MRI scanning;&#xD;
&#xD;
          -  Inability to complete basic fMRI requirements;&#xD;
&#xD;
          -  History of brain surgery or penetrating brain injury;&#xD;
&#xD;
          -  Uncontrolled blood pressure (low or high);&#xD;
&#xD;
          -  Contraindications to tolcapone use (not required for subjects who participate only in&#xD;
             the study arm that does not include study medication);&#xD;
&#xD;
          -  Use of medications or drugs with dopamine-related actions within 30 days;&#xD;
&#xD;
          -  Active substance abuse or dependence;&#xD;
&#xD;
          -  Clinically severe medical illness requiring treatment;&#xD;
&#xD;
          -  History of psychiatric hospitalization (past 1 year) or suicide attempt (past 5&#xD;
             years);&#xD;
&#xD;
          -  Seizures greater than 4 weeks after TBI event or seizures requiring active treatment;&#xD;
&#xD;
          -  History of brain tumor, stroke, Alzheimer's disease, aneurysm rupture, or multiple&#xD;
             sclerosis;&#xD;
&#xD;
          -  History of schizophrenia, ADHD or psychiatric diagnosis EXCEPT depression or PTSD&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew S Kayser, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA Northern California Health Care System, Mather, CA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VA Northern California Health Care System, Mather, CA</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Westphal AJ, Ballard ME, Rodriguez N, Vega TA, D'Esposito M, Kayser AS. Working memory, cortical dopamine tone, and frontoparietal brain recruitment in post-traumatic stress disorder: a randomized controlled trial. Transl Psychiatry. 2021 Jul 12;11(1):389. doi: 10.1038/s41398-021-01512-6.</citation>
    <PMID>34253715</PMID>
  </results_reference>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>October 6, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <last_update_submitted>February 23, 2022</last_update_submitted>
  <last_update_submitted_qc>February 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>concussion</keyword>
  <keyword>traumatic brain injury</keyword>
  <keyword>MRI</keyword>
  <keyword>memory</keyword>
  <keyword>tolcapone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Brain Concussion</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tolcapone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>June 24, 2022</submitted>
    <returned>April 28, 2023</returned>
    <submitted>May 10, 2023</submitted>
  </pending_results>
  <!-- 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/NCT02260570
org study id: D0825-I
secondary id: 1I01RX000825-01
nct id: NCT02260570
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The ability to regulate impulses enables us to plan for the future, to maintain focus in the
      face of distractions (i.e. to encode memories), and to manage emotions. This self regulation
      can be compromised in individuals who have a history of mild traumatic brain injury and
      co-occurring disorders. In this study the investigators are using functional MRI scanning to
      understand how memory and self regulation are expressed in the brains of people with a
      history of mild traumatic brain injury. The investigators are also testing whether the
      medication tolcapone may improve memory and self regulation.
In this randomized, double-blind, placebo-controlled, crossover cognitive neuroscience study,
      the investigators are evaluating whether the COMT inhibitor tolcapone impacts memory and self
      regulation, as measured both behaviorally (via cognitive testing) and neurophysiologically
      (via functional MRI). A new study arm that does not include use of tolcapone, nominally
      equivalent to the placebo arm only, is now also included to address performance on cognitive
      testing alone.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Blood Oxygen Level Dependent (BOLD) brain signal measured using functional MRI
time frame: Approximately 60-240 minutes following tolcapone/placebo administration
description: BOLD signal provides an indirect measure of brain activity during cognitive testing
measure: Performance on Cognitive Testing
time frame: Approximately 60-240 minutes following tolcapone/placebo administration
description: Tasks to assess cognition will be performed while subjects are in the MRI scanner
arm group label: Functional MRI Arm
arm group type: Experimental
description: This cognitive science study consists of a single "arm" in which all subjects receive both tolcapone and placebo in randomized, double-blind, counterbalanced, crossover fashion
intervention type: Drug
intervention name: Tolcapone
description: COMT Inhibitor
arm group label: Functional MRI Arm
other name: Tasmar
intervention type: Drug
intervention name: Placebo
description: A pill that contains no active ingredient
arm group label: Functional MRI Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Andrew S Kayser, MD PhD
role: Principal Investigator
affiliation: VA Northern California Health Care System, Mather, CA
facility: 
country: United States
citation: Westphal AJ, Ballard ME, Rodriguez N, Vega TA, D'Esposito M, Kayser AS. Working memory, cortical dopamine tone, and frontoparietal brain recruitment in post-traumatic stress disorder: a randomized controlled trial. Transl Psychiatry. 2021 Jul 12;11(1):389. doi: 10.1038/s41398-021-01512-6.
PMID: 34253715
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Brain Concussion
mesh term: Tolcapone
sharing ipd: No
submitted: June 24, 2022
returned: April 28, 2023
submitted: May 10, 2023