<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/NCT03273062</url>
  </required_header>
  <id_info>
    <org_study_id>1087860-3</org_study_id>
    <nct_id>NCT03273062</nct_id>
  </id_info>
  <brief_title>A Trial Evaluating Effects of COMT Inhibition in Patients With Acquired Brain Injury</brief_title>
  <official_title>A Double-blind, Placebo-controlled Clinical Trial to Evaluate the Effects of Catechol-O-Methyltransferase (COMT) Inhibition on Cognition and Neuropsychiatric Symptoms in Patients With a History of Acquired Brain Injuries</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sheppard Pratt Health System</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lieber Institute for Brain Development</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sheppard Pratt Health System</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a follow-up study for an ongoing open label trial conducted by the Sheppard&#xD;
      Pratt-Lieber Research Institute utilizing the catechol-O-methyl-transferase (COMT) inhibitor&#xD;
      Tolcapone to evaluate its effects on cognition and neuropsychiatric symptoms in patients with&#xD;
      brain injuries (BI).&#xD;
&#xD;
      In this study, investigators will conduct a double-blind, placebo-controlled clinical trial&#xD;
      utilizing a crossover design to study the effects of two weeks of Tolcapone 200mg&#xD;
      administered three times a day (total of 600mg/day) on cognitive performance. Physical,&#xD;
      emotional, cognitive and social functioning will also be evaluated through participant and&#xD;
      proxy report. The investigators are planning to randomize a total of 12 patients with a&#xD;
      history of acquired brain injury (BI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The proposed study is a follow-up study for an ongoing open label trial conducted by the&#xD;
      Sheppard Pratt-Lieber Research Institute utilizing the catechol-O-methyl-transferase (COMT)&#xD;
      inhibitor Tolcapone to evaluate its effects on cognition and neuropsychiatric symptoms in&#xD;
      patients with brain injuries (BI).&#xD;
&#xD;
      The outcome measures utilized in this study were chosen based on the available data from the&#xD;
      currently ongoing open-label clinical trial. The proposed study will utilize the same study&#xD;
      medication at the same dose and frequency. In addition, the length of administration of study&#xD;
      medication (two weeks) is identical. In the proposed study, investigators will conduct a&#xD;
      double-blind, placebo-controlled clinical trial utilizing a crossover design to study the&#xD;
      effects of two weeks of Tolcapone 200mg administered three times a day (total of 600mg/day)&#xD;
      on cognitive performance. Physical, emotional, cognitive and social functioning will be&#xD;
      evaluated through participant and proxy report. The investigators are planning to randomize a&#xD;
      total of 12 patients with BI.&#xD;
&#xD;
      The cross-over design requires two 2-week long study periods during which the participant&#xD;
      receives either Tolcapone two 100mg capsules three times a day (total of 600mg/day) or&#xD;
      placebo. Participants will be randomly assigned to two sequence groups either starting with&#xD;
      Tolcapone treatment (T-P group) or placebo (P-T group). Investigators and participants will&#xD;
      be blind to the study group assignment and hence blind to the treatment (Tolcapone vs.&#xD;
      placebo) that subjects receive at a given time. The study periods are separated by a &quot;washout&#xD;
      period&quot; that is at least two weeks and maximally 4 weeks long to reduce the potential for&#xD;
      carryover effects. Patient reported outcomes will be obtained a total of four times, twice&#xD;
      prior to the start of each respective study period (Pre-Study Period Visits I &amp; II) as well&#xD;
      as at the end of each study period (Outcome Measures Visits I &amp; II). Cognitive outcome&#xD;
      measures will be obtained twice throughout the study, at the end of each respective study&#xD;
      period (Outcome Measures Visits I &amp; II).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Anticipated">July 20, 2018</completion_date>
  <primary_completion_date type="Anticipated">July 20, 2018</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Interventional clinical trial with a double-blind, randomized placebo-controlled crossover design</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The participant, respective care provider, as well as the investigator and research coordinator (&quot;outcomes assessor&quot;) will all be blind to the order of placebo or medication (Tolcapone) administration in this two-arm, crossover study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>NIH Toolbox Fluid Cognitive Battery</measure>
    <time_frame>Administered on the 14th day of Tolcapone or Placebo treatment (i.e. during each Outcome Measures Visit).</time_frame>
    <description>This battery is a measure of cognitive performance derived from a battery of five cognitive assessments.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>TBI Quality-of-Life Measurement System</measure>
    <time_frame>Administered prior to the start of Tolcapone oe Placebo treatment (i.e. during each Pre-Study Visit) and on the 14th day of Tolcapone or Placebo treatment (i.e. during each Outcome Measures Visit).</time_frame>
    <description>A patient reported outcome measure assessing physical, emotional, cognitive and social functioning. Quality of Life Measure is a computer adaptive questionnaire.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frontal Systems Behavior Scale</measure>
    <time_frame>Administered prior to the start of Tolcapone oe Placebo treatment (i.e. during each Pre-Study Visit) and on the 14th day of Tolcapone or Placebo treatment (i.e. during each Outcome Measures Visit).</time_frame>
    <description>A patient reported outcome measure, and proxy reported outcome measure, assessing neuropsychiatric symptoms associated with prefrontal cortical dysfunction</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">16</enrollment>
  <condition>Brain Injuries</condition>
  <condition>Brain Injuries, Traumatic</condition>
  <condition>Brain Injury, Chronic</condition>
  <arm_group>
    <arm_group_label>Study Period 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>15 days of Tolcapone 200mg TID&#xD;
OR&#xD;
Placebo Comparator 15 days of Placebo pill TID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Study Period 2</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>15 days of Placebo pill TID&#xD;
OR&#xD;
Active Comparator 15 days of Tolcapone 200mg TID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tolcapone 200 MG</intervention_name>
    <description>Tolcapone 200 MG TID</description>
    <arm_group_label>Study Period 1</arm_group_label>
    <arm_group_label>Study Period 2</arm_group_label>
    <other_name>Tasmar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo, TID Placebo will be in capsules that are identical in appearance to intervention drug, Tolcapone.</description>
    <arm_group_label>Study Period 1</arm_group_label>
    <arm_group_label>Study Period 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Capacity for written informed consent&#xD;
&#xD;
          -  Ages 18-70 years, inclusive&#xD;
&#xD;
          -  Diagnosis of a BI including mild, moderate, or severe TBI, or other acquired BI and&#xD;
             post-BI development of neuropsychiatric complaints.&#xD;
&#xD;
          -  Index event resulting in Traumatic or Acquired Brain Injury occurred &gt;12 months prior&#xD;
             to trial initiation&#xD;
&#xD;
          -  A current or former patient at the clinics of the Sheppard Pratt Neuropsychiatry&#xD;
             Program or another Sheppard Pratt outpatient clinic with medical documentation of BI&#xD;
&#xD;
          -  Proficient in the English language&#xD;
&#xD;
          -  Available to come to Sheppard Pratt Towson for the baseline evaluation and testing and&#xD;
             for the duration of the protocol&#xD;
&#xD;
          -  Stable neurological and psychiatric symptomatology for two months prior to trial&#xD;
             initiation as determined by the referring Sheppard Pratt physician.&#xD;
&#xD;
          -  Stable medication dose and regimen for two months prior to trial initiation (based on&#xD;
             a review of medical chart)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of, or active, liver disease or abnormal liver function tests-if the patient&#xD;
             currently has elevated Alanine Transaminase (ALT) or Aspartate Transaminase (AST)&#xD;
             levels that exceed 2 times the upper limit of normal [Normal Reference Ranges ALT&#xD;
             (Male: 4-40 IU/L, Female: 4-40 IU/L), AST (Male: 4-31 IU/L, Female: 4-37 IU/L) or the&#xD;
             ratio of AST: ALT has exceeded 2:1&#xD;
&#xD;
          -  Uncontrolled hypo-or hypertension based on Joint National Committee criteria (JNC7)&#xD;
             Hypotension: Systolic &lt;90mmHg or diastolic &lt;60mmHg Hypertension: Systolic &gt;140mmHg or&#xD;
             diastolic &gt;90 mmHg)&#xD;
&#xD;
          -  Active alcohol use disorder, as defined by DSM-5, of any severity mild, moderate, or&#xD;
             severe&#xD;
&#xD;
          -  Active illicit substance use, resulting in a substance use disorder as defined by&#xD;
             DSM-5, of any severity mild, moderate, or severe&#xD;
&#xD;
          -  Patient is currently taking Tolcapone or any of the following medications that can&#xD;
             interact with Tolcapone resulting in an adverse event: another COMT inhibitor,&#xD;
             benserazide, α-methyldopa, Dobutamine, Apomorphine, Isoproterenol, Clozapine, MAO&#xD;
             inhibitor&#xD;
&#xD;
          -  Known allergy or serious adverse reaction to Tolcapone&#xD;
&#xD;
          -  Participated in any investigational drug trial within the past 30 days.&#xD;
&#xD;
          -  Pregnant or planning to become pregnant during the study period&#xD;
&#xD;
          -  Breastfeeding or planning to breastfeed during the study period.&#xD;
&#xD;
          -  Presence of severe pre-morbid/pre-BI cognitive impairment or behavioral dysfunction,&#xD;
             as per informant or medical documentation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert J Schloesser, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sheppard Pratt Health System</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Robert J Schloesser, MD</last_name>
    <phone>410-938-4610</phone>
    <email>rschloesser@sheppardpratt.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Emily A Berich, BS</last_name>
    <phone>410-938-4610</phone>
    <email>eberich@sheppardpratt.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Sheppard Pratt Health System</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Robert J Schloesser, MD</last_name>
      <phone>410-938-4666</phone>
      <email>rscloesser@sheppardpratt.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <last_update_submitted>September 1, 2017</last_update_submitted>
  <last_update_submitted_qc>September 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sheppard Pratt Health System</investigator_affiliation>
    <investigator_full_name>Robert Schloesser, MD</investigator_full_name>
    <investigator_title>Executive Director, Sheppard Pratt-Lieber Research Institute, Inc.</investigator_title>
  </responsible_party>
  <keyword>Brain Injury</keyword>
  <keyword>Traumatic Brain Injury</keyword>
  <keyword>Acquired Brain Injury</keyword>
  <keyword>Cognition</keyword>
  <keyword>Neuropsychiatric Symptopms</keyword>
  <keyword>COMT</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 Injury, Chronic</mesh_term>
    <mesh_term>Wounds and Injuries</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>
  <!-- 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/NCT03273062
org study id: 1087860-3
nct id: NCT03273062
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a follow-up study for an ongoing open label trial conducted by the Sheppard
      Pratt-Lieber Research Institute utilizing the catechol-O-methyl-transferase (COMT) inhibitor
      Tolcapone to evaluate its effects on cognition and neuropsychiatric symptoms in patients with
      brain injuries (BI).

      In this study, investigators will conduct a double-blind, placebo-controlled clinical trial
      utilizing a crossover design to study the effects of two weeks of Tolcapone 200mg
      administered three times a day (total of 600mg/day) on cognitive performance. Physical,
      emotional, cognitive and social functioning will also be evaluated through participant and
      proxy report. The investigators are planning to randomize a total of 12 patients with a
      history of acquired brain injury (BI).
The proposed study is a follow-up study for an ongoing open label trial conducted by the
      Sheppard Pratt-Lieber Research Institute utilizing the catechol-O-methyl-transferase (COMT)
      inhibitor Tolcapone to evaluate its effects on cognition and neuropsychiatric symptoms in
      patients with brain injuries (BI).

      The outcome measures utilized in this study were chosen based on the available data from the
      currently ongoing open-label clinical trial. The proposed study will utilize the same study
      medication at the same dose and frequency. In addition, the length of administration of study
      medication (two weeks) is identical. In the proposed study, investigators will conduct a
      double-blind, placebo-controlled clinical trial utilizing a crossover design to study the
      effects of two weeks of Tolcapone 200mg administered three times a day (total of 600mg/day)
      on cognitive performance. Physical, emotional, cognitive and social functioning will be
      evaluated through participant and proxy report. The investigators are planning to randomize a
      total of 12 patients with BI.

      The cross-over design requires two 2-week long study periods during which the participant
      receives either Tolcapone two 100mg capsules three times a day (total of 600mg/day) or
      placebo. Participants will be randomly assigned to two sequence groups either starting with
      Tolcapone treatment (T-P group) or placebo (P-T group). Investigators and participants will
      be blind to the study group assignment and hence blind to the treatment (Tolcapone vs.
      placebo) that subjects receive at a given time. The study periods are separated by a "washout
      period" that is at least two weeks and maximally 4 weeks long to reduce the potential for
      carryover effects. Patient reported outcomes will be obtained a total of four times, twice
      prior to the start of each respective study period (Pre-Study Period Visits I & II) as well
      as at the end of each study period (Outcome Measures Visits I & II). Cognitive outcome
      measures will be obtained twice throughout the study, at the end of each respective study
      period (Outcome Measures Visits I & II).
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Interventional clinical trial with a double-blind, randomized placebo-controlled crossover design
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The participant, respective care provider, as well as the investigator and research coordinator ("outcomes assessor") will all be blind to the order of placebo or medication (Tolcapone) administration in this two-arm, crossover study.
measure: NIH Toolbox Fluid Cognitive Battery
time frame: Administered on the 14th day of Tolcapone or Placebo treatment (i.e. during each Outcome Measures Visit).
description: This battery is a measure of cognitive performance derived from a battery of five cognitive assessments.
measure: TBI Quality-of-Life Measurement System
time frame: Administered prior to the start of Tolcapone oe Placebo treatment (i.e. during each Pre-Study Visit) and on the 14th day of Tolcapone or Placebo treatment (i.e. during each Outcome Measures Visit).
description: A patient reported outcome measure assessing physical, emotional, cognitive and social functioning. Quality of Life Measure is a computer adaptive questionnaire.
measure: Frontal Systems Behavior Scale
time frame: Administered prior to the start of Tolcapone oe Placebo treatment (i.e. during each Pre-Study Visit) and on the 14th day of Tolcapone or Placebo treatment (i.e. during each Outcome Measures Visit).
description: A patient reported outcome measure, and proxy reported outcome measure, assessing neuropsychiatric symptoms associated with prefrontal cortical dysfunction
arm group label: Study Period 1
arm group type: Active Comparator
description: 15 days of Tolcapone 200mg TID
OR
Placebo Comparator 15 days of Placebo pill TID
arm group label: Study Period 2
arm group type: Placebo Comparator
description: 15 days of Placebo pill TID
OR
Active Comparator 15 days of Tolcapone 200mg TID
intervention type: Drug
intervention name: Tolcapone 200 MG
description: Tolcapone 200 MG TID
arm group label: Study Period 1
arm group label: Study Period 2
other name: Tasmar
intervention type: Other
intervention name: Placebo
description: Placebo, TID Placebo will be in capsules that are identical in appearance to intervention drug, Tolcapone.
arm group label: Study Period 1
arm group label: Study Period 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Robert J Schloesser, MD
role: Principal Investigator
affiliation: Sheppard Pratt Health System
last name: Robert J Schloesser, MD
phone: 410-938-4610
email: rschloesser@sheppardpratt.org
last name: Emily A Berich, BS
phone: 410-938-4610
email: eberich@sheppardpratt.org
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Sheppard Pratt Health System
investigator full name: Robert Schloesser, MD
investigator title: Executive Director, Sheppard Pratt-Lieber Research Institute, Inc.
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Brain Injury, Chronic
mesh term: Wounds and Injuries
mesh term: Tolcapone
sharing ipd: No