<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/NCT02211820</url>
  </required_header>
  <id_info>
    <org_study_id>140164</org_study_id>
    <secondary_id>14-M-0164</secondary_id>
    <nct_id>NCT02211820</nct_id>
  </id_info>
  <brief_title>PET Imaging in Chronic Traumatic Encephalopathy</brief_title>
  <official_title>PET Imaging in Chronic Traumatic Encephalopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Chronic traumatic encephalopathy (CTE) is a brain disease caused in part by head injury.&#xD;
      The brain changes from CTE can only be seen at autopsy. Researchers want to test a new brain&#xD;
      scan to help diagnose CTE in living patients.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      - To determine if a new type of brain scan can detect changes that occur in chronic traumatic&#xD;
      encephalopathy.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Adults age 18 60 with previous head injury or participation in certain sports.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with:&#xD;
&#xD;
        -  Physical exam&#xD;
&#xD;
        -  Blood and urine tests&#xD;
&#xD;
        -  Tests of thinking, mood, and memory&#xD;
&#xD;
        -  30-minute magnetic resonance imaging (MRI) brain scan. A magnetic field and radio waves&#xD;
           take pictures of the brain. Participants will lie on a table that slides into a metal&#xD;
           cylinder. They will get earplugs for the loud knocking sounds.&#xD;
&#xD;
        -  Visit 1: Participants will have a 70-minute PET scan of the brain with a small amount of&#xD;
           a radioactive chemical. That will be injected through an intravenous tube (catheter) in&#xD;
           each arm. A catheter will also be put into an artery at the wrist or elbow.&#xD;
&#xD;
        -  Participants will lie on a bed that slides in and out of a donut-shaped scanner. A&#xD;
           plastic mask may be molded to their face and head. Vital signs and heart activity will&#xD;
           be checked before and during the scan.&#xD;
&#xD;
        -  Blood and urine will be taken before and after the scan.&#xD;
&#xD;
        -  Participants will be checked on by phone the next day.&#xD;
&#xD;
        -  Visit 2: Participants will repeat Visit 1 with a different chemical and no artery&#xD;
           catheter.&#xD;
&#xD;
        -  Visit 3: Participants may have a spinal tap. Some fluid will be removed by needle&#xD;
           between the bones in the back.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective: To determine if the PET radioligand [11C]PBB3 can detect aggregates of tau protein&#xD;
      in the brains of patients with history of traumatic brain injury (TBI) and suspected chronic&#xD;
      traumatic encephalopathy (CTE).&#xD;
&#xD;
      Study population: The proposed study will include 40 subjects. Twenty will be patients with&#xD;
      history of TBI and suspected CTE and 20 will be healthy cognitively normal volunteers without&#xD;
      history of TBI.&#xD;
&#xD;
      Design: Subjects will undergo medical screening and have brain MRI and neuropsychological&#xD;
      testing performed. Subjects will undergo one brain PET scan with [11C]PBB3 to detect&#xD;
      aggregates of tau protein. Subjects will also have one brain PET scan with [11C]Pittsburgh&#xD;
      compound B (PIB) to detect amyloid plaques. Subjects will be asked to have a lumbar puncture&#xD;
      to measure CSF tau concentrations.&#xD;
&#xD;
      Outcome measures: The primary outcome measure will be the amount of [11C]PBB3 binding in the&#xD;
      brain. We will quantify the radioligand s brain uptake, washout, plasma clearance, and&#xD;
      distribution volume using compartmental modeling. Distribution volume of [11C]PBB3 is&#xD;
      proportional to the density of insoluble paired helical filaments of tau and is equal to the&#xD;
      ratio at equilibrium of uptake in brain to the concentration of parent radiotracer in plasma.&#xD;
      As an exploratory measure, we will determine if there is a relationship between [11C]PBB3&#xD;
      binding in brain and gray matter loss on MRI. We will also measure the amount of [11C]PIB&#xD;
      binding in the brain using the Logan reference tissue method with cerebellum as reference.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 1, 2014</start_date>
  <completion_date type="Actual">October 12, 2016</completion_date>
  <primary_completion_date type="Actual">June 20, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Amount of 11C-PBB3 binding in brain as measured with PET</measure>
    <time_frame>1 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Amount of brain atrophy as measured with MRI.Amount of 11C-PIB binding in brain as measured with PET</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">6</enrollment>
  <condition>Brain Disease</condition>
  <condition>Brain Mapping</condition>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&lt;TAB&gt;&#xD;
&#xD;
        &lt;TAB&gt;&#xD;
&#xD;
          -  For patients:&#xD;
&#xD;
               -  History of head injury resulting from past or current participation in one or&#xD;
                  more contact sports (hockey, football, or boxing). Patients may have history of&#xD;
                  structural brain injury (i.e., injury accompanying abnormality on MRI or CT&#xD;
                  scan), concussion without structural injury (mild TBI), or repetitive&#xD;
                  sub-concussive injury.&#xD;
&#xD;
               -  Meets DMS-V criteria for Major Neurocognitive Disorder or Mild Neurocognitive&#xD;
                  Disorder&#xD;
&#xD;
               -  Age 18 to 60 years.&#xD;
&#xD;
               -  Ambulatory.&#xD;
&#xD;
               -  Patients unable to provide informed consent must have a surrogate decision maker.&#xD;
&#xD;
          -  For healthy controls:&#xD;
&#xD;
               -  Healthy without past or present history of brain disease.&#xD;
&#xD;
               -  Age 18 to 60 years.&#xD;
&#xD;
               -  Able to provide informed consent.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Past or present history of a brain disorder other than TBI.&#xD;
&#xD;
          -  For patients: Subjects with abnormal brain imaging findings that suggest a diagnosis&#xD;
             other than TBI or a second lesion such as brain tumor in addition to the changes&#xD;
             consistent with TBI.&#xD;
&#xD;
          -  For controls: past or present history of either a single concussion or more severe&#xD;
             TBI, or of repetitive sub-concussive injury due to contact sport participation.&#xD;
&#xD;
          -  Serious medical conditions, which make study procedures of the current study unsafe.&#xD;
             Such serious medical conditions include uncontrolled epilepsy and multiple serious&#xD;
             injuries. The Principal Investigator of this protocol will determine whether the&#xD;
             subject needs to be excluded.&#xD;
&#xD;
          -  The DSM-V criteria for Major Neurocognitive Disorder are as follows:&#xD;
&#xD;
             --Evidence of significant cognitive decline from a previous level of performance in&#xD;
             one or more cognitive domains (complex attention, executive function, learning and&#xD;
             memory, perceptual-motor, or social cognition) based on:&#xD;
&#xD;
               -  Concern of the individual, a knowledgeable informant, of the clinician that there&#xD;
                  has been a significant decline in cognitive function.&#xD;
&#xD;
               -  A substantial impairment in cognitive performance, preferably documented by&#xD;
                  standardized neuropsychological testing, or, in its absence, another qualified&#xD;
                  clinical assessment.&#xD;
&#xD;
          -  The cognitive deficits interfere with independence in everyday activities (i.e. at a&#xD;
             minimum, requiring assistance with complex instrumental activities of daily living&#xD;
             such as paying bills or managing medications)&#xD;
&#xD;
          -  The cognitive deficits do not occur exclusively in the context of delirium.&#xD;
&#xD;
          -  The cognitive disorder is not better explained by another mental disorder (e.g. major&#xD;
             depressive disorder, schizophrenia).&#xD;
&#xD;
          -  Criteria for Mild Neurocognitive Disorder are as follows:&#xD;
&#xD;
               -  There is evidence of modest cognitive decline from a previous level of&#xD;
                  performance in one or more of the domains outlined above based on:&#xD;
&#xD;
                    -  Concern of the individual, a knowledgeable informant, or the clinician.&#xD;
&#xD;
                    -  Decline in neurocognitive performance, preferably documented by standardized&#xD;
                       neuropsychological testing, or, in its absence, another qualified clinical&#xD;
                       assessment.&#xD;
&#xD;
               -  The cognitive deficits are insufficient to interfere with independence (eg,&#xD;
                  instrumental activities of daily living, like more complex tasks such as paying&#xD;
                  bills or managing medications,&#xD;
&#xD;
        are preserved), but greater effort, compensatory strategies, or accommodation may be&#xD;
        required to maintain independence.&#xD;
&#xD;
          -  The cognitive deficits do not occur exclusively in the context of a delirium.&#xD;
&#xD;
          -  The cognitive deficits are not primarily attributable to another mental disorder (eg,&#xD;
             major depressive disorder, schizophrenia).&#xD;
&#xD;
        There are no restrictions on medications. Since disease modifying therapy for tauopathies&#xD;
        (including CTE and Alzheimer s disease) do not currently exist, no currently available&#xD;
        medications, either prescribed or over-the-counter, are expected to confound the results of&#xD;
        this study. Anti-inflammatory medications, including NSAIDs, are not expected to&#xD;
        significantly reduce tau aggregation in CTE patients, based on the failure of these&#xD;
        medications to prevent disease progression in Alzheimer s disease.&#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_official>
    <last_name>Robert B Innis, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Mental Health (NIMH)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center, 9000 Rockville Pike</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Baugh CM, Stamm JM, Riley DO, Gavett BE, Shenton ME, Lin A, Nowinski CJ, Cantu RC, McKee AC, Stern RA. Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav. 2012 Jun;6(2):244-54. doi: 10.1007/s11682-012-9164-5.</citation>
    <PMID>22552850</PMID>
  </reference>
  <reference>
    <citation>Braskie MN, Klunder AD, Hayashi KM, Protas H, Kepe V, Miller KJ, Huang SC, Barrio JR, Ercoli LM, Siddarth P, Satyamurthy N, Liu J, Toga AW, Bookheimer SY, Small GW, Thompson PM. Plaque and tangle imaging and cognition in normal aging and Alzheimer's disease. Neurobiol Aging. 2010 Oct;31(10):1669-78. doi: 10.1016/j.neurobiolaging.2008.09.012. Epub 2008 Nov 11.</citation>
    <PMID>19004525</PMID>
  </reference>
  <reference>
    <citation>Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34(2):457-68. doi: 10.3233/JAD-122059.</citation>
    <PMID>23234879</PMID>
  </reference>
  <verification_date>October 12, 2016</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>July 3, 2018</last_update_submitted>
  <last_update_submitted_qc>July 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Encephalopathy</keyword>
  <keyword>Imaging Studies</keyword>
  <keyword>Dementia</keyword>
  <keyword>Cerebellar Cortical Atrophy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Chronic Traumatic Encephalopathy</mesh_term>
  </condition_browse>
  <!-- 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/NCT02211820
org study id: 140164
secondary id: 14-M-0164
nct id: NCT02211820
lead sponsor: 
Background:

      - Chronic traumatic encephalopathy (CTE) is a brain disease caused in part by head injury.
      The brain changes from CTE can only be seen at autopsy. Researchers want to test a new brain
      scan to help diagnose CTE in living patients.

      Objective:

      - To determine if a new type of brain scan can detect changes that occur in chronic traumatic
      encephalopathy.

      Eligibility:

      - Adults age 18 60 with previous head injury or participation in certain sports.

      Design:

        -  Participants will be screened with:

        -  Physical exam

        -  Blood and urine tests

        -  Tests of thinking, mood, and memory

        -  30-minute magnetic resonance imaging (MRI) brain scan. A magnetic field and radio waves
           take pictures of the brain. Participants will lie on a table that slides into a metal
           cylinder. They will get earplugs for the loud knocking sounds.

        -  Visit 1: Participants will have a 70-minute PET scan of the brain with a small amount of
           a radioactive chemical. That will be injected through an intravenous tube (catheter) in
           each arm. A catheter will also be put into an artery at the wrist or elbow.

        -  Participants will lie on a bed that slides in and out of a donut-shaped scanner. A
           plastic mask may be molded to their face and head. Vital signs and heart activity will
           be checked before and during the scan.

        -  Blood and urine will be taken before and after the scan.

        -  Participants will be checked on by phone the next day.

        -  Visit 2: Participants will repeat Visit 1 with a different chemical and no artery
           catheter.

        -  Visit 3: Participants may have a spinal tap. Some fluid will be removed by needle
           between the bones in the back.
Objective: To determine if the PET radioligand [11C]PBB3 can detect aggregates of tau protein
      in the brains of patients with history of traumatic brain injury (TBI) and suspected chronic
      traumatic encephalopathy (CTE).

      Study population: The proposed study will include 40 subjects. Twenty will be patients with
      history of TBI and suspected CTE and 20 will be healthy cognitively normal volunteers without
      history of TBI.

      Design: Subjects will undergo medical screening and have brain MRI and neuropsychological
      testing performed. Subjects will undergo one brain PET scan with [11C]PBB3 to detect
      aggregates of tau protein. Subjects will also have one brain PET scan with [11C]Pittsburgh
      compound B (PIB) to detect amyloid plaques. Subjects will be asked to have a lumbar puncture
      to measure CSF tau concentrations.

      Outcome measures: The primary outcome measure will be the amount of [11C]PBB3 binding in the
      brain. We will quantify the radioligand s brain uptake, washout, plasma clearance, and
      distribution volume using compartmental modeling. Distribution volume of [11C]PBB3 is
      proportional to the density of insoluble paired helical filaments of tau and is equal to the
      ratio at equilibrium of uptake in brain to the concentration of parent radiotracer in plasma.
      As an exploratory measure, we will determine if there is a relationship between [11C]PBB3
      binding in brain and gray matter loss on MRI. We will also measure the amount of [11C]PIB
      binding in the brain using the Logan reference tissue method with cerebellum as reference.
observational model: Cohort
time perspective: Prospective
measure: Amount of 11C-PBB3 binding in brain as measured with PET
time frame: 1 year
measure: Amount of brain atrophy as measured with MRI.Amount of 11C-PIB binding in brain as measured with PET
time frame: 1 year
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Robert B Innis, M.D.
role: Principal Investigator
affiliation: National Institute of Mental Health (NIMH)
facility: 
country: United States
citation: Baugh CM, Stamm JM, Riley DO, Gavett BE, Shenton ME, Lin A, Nowinski CJ, Cantu RC, McKee AC, Stern RA. Chronic traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav. 2012 Jun;6(2):244-54. doi: 10.1007/s11682-012-9164-5.
PMID: 22552850
citation: Braskie MN, Klunder AD, Hayashi KM, Protas H, Kepe V, Miller KJ, Huang SC, Barrio JR, Ercoli LM, Siddarth P, Satyamurthy N, Liu J, Toga AW, Bookheimer SY, Small GW, Thompson PM. Plaque and tangle imaging and cognition in normal aging and Alzheimer's disease. Neurobiol Aging. 2010 Oct;31(10):1669-78. doi: 10.1016/j.neurobiolaging.2008.09.012. Epub 2008 Nov 11.
PMID: 19004525
citation: Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34(2):457-68. doi: 10.3233/JAD-122059.
PMID: 23234879
responsible party type: Sponsor
mesh term: Brain Diseases
mesh term: Brain Injuries, Traumatic
mesh term: Chronic Traumatic Encephalopathy