<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/NCT02191267</url>
  </required_header>
  <id_info>
    <org_study_id>2014P000035</org_study_id>
    <nct_id>NCT02191267</nct_id>
  </id_info>
  <brief_title>Tau Imaging of Chronic Traumatic Encephalopathy</brief_title>
  <official_title>Tau Imaging of Chronic Traumatic Encephalopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>U.S. Army Medical Research and Development Command</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>Boston University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Chronic traumatic encephalopathy (CTE) is a progressive degenerative brain disease with&#xD;
      symptoms that include memory loss, problems with impulse control, and depression that can&#xD;
      lead to suicide. As the disease progresses, it can lead to dementia. Currently CTE can only&#xD;
      be diagnosed postmortem where an over-accumulation of a protein called tau is observed. There&#xD;
      is now a new experimental measure that makes it possible, for the first time, to measure tau&#xD;
      protein in the living human brain using a novel positron emission tomography (PET) ligand,&#xD;
      [F-18] AV-1451 (aka, [18F]-T807).&#xD;
&#xD;
      The main objective of this study is to use a novel PET approach to measure tau accumulation&#xD;
      in the brain. The presence of CTE at autopsy in deceased National Football League (NFL)&#xD;
      players has been well documented. Accordingly, we will conduct this study in a group of&#xD;
      retired NFL players who have clinical symptoms of CTE and are suspected of having CTE based&#xD;
      on high levels of tau in their spinal fluid and abnormalities seen on research brain scans.&#xD;
      We will compare them with a control group of former elite level athletes who have not&#xD;
      experienced any brain trauma, deny any clinical symptoms, and who have completely normal&#xD;
      spinal fluid tau and amyloid levels, and brain scans. We will also include a group of&#xD;
      subjects with AD. All participants will be recruited from ongoing studies, headed by the&#xD;
      Partnering PI of this proposal, Dr. Robert Stern, at the Boston University Center for the&#xD;
      Study of Traumatic Encephalopathy and the Alzheimer's Disease Center. We will use both a beta&#xD;
      amyloid PET scan ([18F]-florbetapir) and a tau PET scan ([18F]-T807) on consecutive days.&#xD;
      With the beta amyloid scan we expect little or no evidence of amyloid in the NFL players with&#xD;
      presumed CTE, and no evidence of amyloid in the control group of athletes with no history of&#xD;
      repetitive brain trauma. In contrast we expect to see beta amyloid accumulation in the AD&#xD;
      patient brains. With the new tau ligand, we expect that the NFL players with presumed CTE&#xD;
      will show elevated levels of tau protein in the brain, which will not be observed in athletes&#xD;
      without a history of brain trauma, but which will be seen in the AD patients' brains.&#xD;
&#xD;
      Another goal is to use the latest MRI technologies to develop specific tau imaging biomarkers&#xD;
      that correlate with the PET and spinal fluid tau measures but without the radiation of PET or&#xD;
      invasiveness of spinal taps. The development of these surrogate imaging markers of tau, is&#xD;
      critically important to diagnosing CTE. This in turn will lead to studies relevant to&#xD;
      treatment and prevention of this devastating disease. Finally, as an exploratory method of&#xD;
      examining possible genetic risk for CTE, we will also use cutting edge genetic analysis of&#xD;
      blood samples from subjects in this proposal and compare tau load, measured by PET tau ligand&#xD;
      uptake and cerebrospinal fluid (CSF) p-tau level, with a measure of genetic susceptibility to&#xD;
      tau load, referred to as the genetic risk score for tau.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">September 30, 2016</completion_date>
  <primary_completion_date type="Actual">September 30, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Tau Protein Uptake..</measure>
    <time_frame>Day 1 - of 2 day study.</time_frame>
    <description>Whole brain mean (and standard deviation) cortical value derived from standardized uptake value ratio (SUVr). Each [F18]-T807 tau scan consisted of a 60-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-T807, followed by a second 20-minute dynamic imaging (list mode) acquisition from 80-100 minutes. SUVr images were constructed from the sum of the 80-100 minute frames resulting in late SUVr distribution maps.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Beta-Amyloid (Aβ) Protein Uptake.</measure>
    <time_frame>Day 2 - of 2 day study.</time_frame>
    <description>Mean and standard deviation for standardized uptake value ratios (SUVr) for posterior cingulate, superior parietal, lateral frontal, medial frontal, lateral temporal, and occipital brain regions. Each [F18]-Florbetapir (Beta-Amyloid) scan consisted of a 70-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-Florbetapir. SUVr images were constructed from the sum of the 50-70 minute frames resulting in late SUVr distribution maps.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Chronic Traumatic Encephalopathy</condition>
  <arm_group>
    <arm_group_label>Presumed CTE Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, MRI/MRS Scans, and Genetic Analysis for Genetic Risk Score for Tau.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Interventions administered to the Control Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, and MRI/MRS Scans.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AD Dementia Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, MRI/MRS Scans</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>[F18]-T807</intervention_name>
    <description>[F18]-T807 PET Scan to measure tau deposition in the brain.</description>
    <arm_group_label>AD Dementia Group</arm_group_label>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Presumed CTE Group</arm_group_label>
    <other_name>[F-18] AV-1451</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>[F18]-Florbetapir</intervention_name>
    <description>[F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
    <arm_group_label>AD Dementia Group</arm_group_label>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Presumed CTE Group</arm_group_label>
    <other_name>Amyvid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI/MRS</intervention_name>
    <description>Two scans (structural, diffusion tensor imaging, and susceptibility weighted imaging scanned as part of one MR protocol, and a one-dimensional and two-dimensional spectroscopy examination as part of the other MR protocol.</description>
    <arm_group_label>AD Dementia Group</arm_group_label>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Presumed CTE Group</arm_group_label>
    <other_name>Magnetic Resonance Imaging</other_name>
    <other_name>Magnetic Resonance Spectroscopy</other_name>
    <other_name>Diffusion Tensor Imaging</other_name>
    <other_name>Susceptibility Weighted Imgaging</other_name>
    <other_name>One-dimensional Spectroscopy</other_name>
    <other_name>Two-dimensional Spectroscopy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Genetic Analysis for Genetic Risk Score for Tau.</intervention_name>
    <description>DNA will be extracted from previously acquired and de-identified frozen blood specimens using a standard protocol (Gentra Puregene Kit, Qiagen 158422). Genotyping will be performed using the iPLEX Sequenom MassARRAY platform and samples will be genotyped for single nucleotide polymorphisms (SNPs) associated with the deposition of neurofibrillary tangles.</description>
    <arm_group_label>Presumed CTE Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1. Presumed CTE Group (includes 20 former NFL players who will have already participated&#xD;
             in the NIH-funded R01 &quot;DETECT&quot; (Diagnosis and Evaluation of Traumatic Encephalopathy&#xD;
             with Clinical Tests) study (Stern, PI; Shenton, Neuroimaging Site PI). Eligibility&#xD;
             criteria for presumed CTE group and the control group are based on findings from the&#xD;
             DETECT study.&#xD;
&#xD;
             Inclusion Criteria:&#xD;
&#xD;
               -  significant cognitive impairment (and impairment in at least one of the&#xD;
                  following):&#xD;
&#xD;
               -  behavioral (e.g., impulsivity, aggression),&#xD;
&#xD;
               -  mood (e.g., elevated depression measures, elevated suicidality),&#xD;
&#xD;
               -  and/or motor (e.g., impairments evidenced in neurological examination;&#xD;
&#xD;
               -  demonstrated abnormalities on svMRI, DTI, or MRS&#xD;
&#xD;
             Exclusion Criteria:&#xD;
&#xD;
               -  weight &gt; 350 lbs&#xD;
&#xD;
               -  known metallic implants preventing MRI&#xD;
&#xD;
               -  history of stroke&#xD;
&#xD;
               -  non-English speaking&#xD;
&#xD;
               -  significant vision or hearing impairment&#xD;
&#xD;
               -  unable to provide written informed consent&#xD;
&#xD;
          2. Control Group (comprised of 5 male participants selected from 50 control subjects in&#xD;
             the DETECT study).&#xD;
&#xD;
             Inclusion Criteria:&#xD;
&#xD;
               -  no history of mTBI or exposure to repetitive brain trauma&#xD;
&#xD;
               -  normal functioning on DETECT clinical measures&#xD;
&#xD;
               -  no abnormalities on svMRI, DTI, or MRS&#xD;
&#xD;
             Exclusion Criteria:&#xD;
&#xD;
               -  weight &gt; 350 lbs&#xD;
&#xD;
               -  known metallic implants preventing MRI&#xD;
&#xD;
               -  history of stroke or other neurological disease&#xD;
&#xD;
               -  non-English speaking&#xD;
&#xD;
               -  significant vision or hearing impairment&#xD;
&#xD;
          3. AD Dementia Group (comprised of 5 male participants recruited from the BU Alzheimer's&#xD;
             Disease Center (ADC) Clinical Core Registry (Dr. Stern, PI).&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  diagnosis of Dementia due to AD using the NIA-AA (National Institute on&#xD;
             Aging-Alzheimer's Association) criteria&#xD;
&#xD;
          -  Clinical Dementia Rating Global Score of 1.0,&#xD;
&#xD;
          -  a positive florbetapir PET study,&#xD;
&#xD;
          -  CSF p-tau/Aβ consistent with AD.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  history of TBI, mTBI or or exposure to repetitive brain trauma&#xD;
&#xD;
          -  weight &gt; 350 lbs&#xD;
&#xD;
          -  known metallic implants preventing MRI&#xD;
&#xD;
          -  history of stroke or other neurological disease&#xD;
&#xD;
          -  non-English speaking&#xD;
&#xD;
          -  significant vision or hearing impairment&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Martha E. Shenton, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Boston University Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Zhang W, Arteaga J, Cashion DK, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Szardenings AK, Wang E, Walsh JC, Xia C, Yu C, Zhao T, Kolb HC. A highly selective and specific PET tracer for imaging of tau pathologies. J Alzheimers Dis. 2012;31(3):601-12. doi: 10.3233/JAD-2012-120712.</citation>
    <PMID>22683529</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>April 2018</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 16, 2014</study_first_posted>
  <results_first_submitted>March 15, 2018</results_first_submitted>
  <results_first_submitted_qc>April 19, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">May 17, 2018</results_first_posted>
  <last_update_submitted>April 19, 2018</last_update_submitted>
  <last_update_submitted_qc>April 19, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Martha E Shenton</investigator_full_name>
    <investigator_title>Director, Psychiatry Neuroimaging Laboratory</investigator_title>
  </responsible_party>
  <keyword>CTE</keyword>
  <keyword>Positron Emission Topography</keyword>
  <keyword>Tau</keyword>
  <keyword>Beta-amyloid</keyword>
  <keyword>Magnetic Resonance Imaging</keyword>
  <keyword>Magnetic Resonance Spectroscopy</keyword>
  <keyword>Diffusion Tensor Imaging</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>

  <clinical_results>

    <participant_flow>
      <recruitment_details>24 subjects at presumed risk for Chronic Traumatic Encephalopathy (CTE), 6 healthy control subjects without a history of repetitive brain trauma, and 4 Alzheimer's Disease (AD) subjects were recruited from the Boston University Center for the study of Chronic Traumatic Encephalopathy.</recruitment_details>
      <pre_assignment_details>Subjects were pre-assigned according to previously assigned study diagnostic status based on prior participation in studies at the Boston Center for the study of Chronic Traumatic Encephalopathy.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Presumed CTE Group</title>
          <description>Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
        </group>
        <group group_id="P2">
          <title>Control Group</title>
          <description>Interventions administered to the Control Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
        </group>
        <group group_id="P3">
          <title>AD Dementia Group</title>
          <description>Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Presumed CTE Group</title>
          <description>Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
        </group>
        <group group_id="B2">
          <title>Control Group</title>
          <description>Interventions administered to the Control Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
        </group>
        <group group_id="B3">
          <title>AD Dementia Group</title>
          <description>Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="19"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="29"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Tau Protein Uptake..</title>
        <description>Whole brain mean (and standard deviation) cortical value derived from standardized uptake value ratio (SUVr). Each [F18]-T807 tau scan consisted of a 60-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-T807, followed by a second 20-minute dynamic imaging (list mode) acquisition from 80-100 minutes. SUVr images were constructed from the sum of the 80-100 minute frames resulting in late SUVr distribution maps.</description>
        <time_frame>Day 1 - of 2 day study.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Presumed CTE Group</title>
            <description>Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
          </group>
          <group group_id="O2">
            <title>Control Group</title>
            <description>Interventions administered to the Control Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
          </group>
          <group group_id="O3">
            <title>AD Dementia Group</title>
            <description>Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Tau Protein Uptake..</title>
          <description>Whole brain mean (and standard deviation) cortical value derived from standardized uptake value ratio (SUVr). Each [F18]-T807 tau scan consisted of a 60-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-T807, followed by a second 20-minute dynamic imaging (list mode) acquisition from 80-100 minutes. SUVr images were constructed from the sum of the 80-100 minute frames resulting in late SUVr distribution maps.</description>
          <units>SUVr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1871" spread="0.0762"/>
                    <measurement group_id="O2" value="1.1652" spread="0.0670"/>
                    <measurement group_id="O3" value="1.5910" spread="0.3807"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Beta-Amyloid (Aβ) Protein Uptake.</title>
        <description>Mean and standard deviation for standardized uptake value ratios (SUVr) for posterior cingulate, superior parietal, lateral frontal, medial frontal, lateral temporal, and occipital brain regions. Each [F18]-Florbetapir (Beta-Amyloid) scan consisted of a 70-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-Florbetapir. SUVr images were constructed from the sum of the 50-70 minute frames resulting in late SUVr distribution maps.</description>
        <time_frame>Day 2 - of 2 day study.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Presumed CTE Group</title>
            <description>Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
          </group>
          <group group_id="O2">
            <title>Control Group</title>
            <description>Interventions administered to the Control Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
          </group>
          <group group_id="O3">
            <title>AD Dementia Group</title>
            <description>Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Beta-Amyloid (Aβ) Protein Uptake.</title>
          <description>Mean and standard deviation for standardized uptake value ratios (SUVr) for posterior cingulate, superior parietal, lateral frontal, medial frontal, lateral temporal, and occipital brain regions. Each [F18]-Florbetapir (Beta-Amyloid) scan consisted of a 70-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-Florbetapir. SUVr images were constructed from the sum of the 50-70 minute frames resulting in late SUVr distribution maps.</description>
          <units>SUVr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Posterior Cingulate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.346" spread="0.215"/>
                    <measurement group_id="O2" value="1.290" spread="0.068"/>
                    <measurement group_id="O3" value="1.760" spread="0.352"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Superior Parietal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.225" spread="0.180"/>
                    <measurement group_id="O2" value="1.118" spread="0.073"/>
                    <measurement group_id="O3" value="1.708" spread="1.708"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lateral Frontal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.196" spread="0.178"/>
                    <measurement group_id="O2" value="1.145" spread="0.085"/>
                    <measurement group_id="O3" value="1.728" spread="0.291"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Medial Frontal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.253" spread="0.190"/>
                    <measurement group_id="O2" value="1.182" spread="0.083"/>
                    <measurement group_id="O3" value="1.847" spread="0.261"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lateral Temporal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.178" spread="0.164"/>
                    <measurement group_id="O2" value="1.113" spread="0.083"/>
                    <measurement group_id="O3" value="1.766" spread="0.345"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Occipital</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.288" spread="0.191"/>
                    <measurement group_id="O2" value="1.157" spread="0.039"/>
                    <measurement group_id="O3" value="1.540" spread="1.540"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Through study completion, Subjects were assessed for adverse effects immediately following each scan (On Day 1 and Day 2) and again by telephone 72 hours following study participation. Thus, assessment for adverse events were made over over a 5-day period which included Days 1 and 2 of the study visit and a follow-up telephone assessment on Day 5.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Presumed CTE Group</title>
          <description>Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
        </group>
        <group group_id="E2">
          <title>Control Group</title>
          <description>Interventions administered to the Control Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
        </group>
        <group group_id="E3">
          <title>AD Dementia Group</title>
          <description>Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan and [F18]-Florbetapir PET Scan.&#xD;
[F18]-T807: [F18]-T807 PET Scan to measure tau deposition in the brain.&#xD;
[F18]-Florbetapir: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Exploratory aims including potential MRI and MRS biomarkers and genetic analysis for genetic risk score for Tau will also be analyzed but are not primary or secondary outcome measures.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Martha Shenton</name_or_title>
      <organization>Brigham and Women's Hospital</organization>
      <phone>617-699-6152</phone>
      <email>shenton@bwh.harvard.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02191267
org study id: 2014P000035
nct id: NCT02191267
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Chronic traumatic encephalopathy (CTE) is a progressive degenerative brain disease with
      symptoms that include memory loss, problems with impulse control, and depression that can
      lead to suicide. As the disease progresses, it can lead to dementia. Currently CTE can only
      be diagnosed postmortem where an over-accumulation of a protein called tau is observed. There
      is now a new experimental measure that makes it possible, for the first time, to measure tau
      protein in the living human brain using a novel positron emission tomography (PET) ligand,
      [F-18] AV-1451 (aka, [18F]-T807).

      The main objective of this study is to use a novel PET approach to measure tau accumulation
      in the brain. The presence of CTE at autopsy in deceased National Football League (NFL)
      players has been well documented. Accordingly, we will conduct this study in a group of
      retired NFL players who have clinical symptoms of CTE and are suspected of having CTE based
      on high levels of tau in their spinal fluid and abnormalities seen on research brain scans.
      We will compare them with a control group of former elite level athletes who have not
      experienced any brain trauma, deny any clinical symptoms, and who have completely normal
      spinal fluid tau and amyloid levels, and brain scans. We will also include a group of
      subjects with AD. All participants will be recruited from ongoing studies, headed by the
      Partnering PI of this proposal, Dr. Robert Stern, at the Boston University Center for the
      Study of Traumatic Encephalopathy and the Alzheimer's Disease Center. We will use both a beta
      amyloid PET scan ([18F]-florbetapir) and a tau PET scan ([18F]-T807) on consecutive days.
      With the beta amyloid scan we expect little or no evidence of amyloid in the NFL players with
      presumed CTE, and no evidence of amyloid in the control group of athletes with no history of
      repetitive brain trauma. In contrast we expect to see beta amyloid accumulation in the AD
      patient brains. With the new tau ligand, we expect that the NFL players with presumed CTE
      will show elevated levels of tau protein in the brain, which will not be observed in athletes
      without a history of brain trauma, but which will be seen in the AD patients' brains.

      Another goal is to use the latest MRI technologies to develop specific tau imaging biomarkers
      that correlate with the PET and spinal fluid tau measures but without the radiation of PET or
      invasiveness of spinal taps. The development of these surrogate imaging markers of tau, is
      critically important to diagnosing CTE. This in turn will lead to studies relevant to
      treatment and prevention of this devastating disease. Finally, as an exploratory method of
      examining possible genetic risk for CTE, we will also use cutting edge genetic analysis of
      blood samples from subjects in this proposal and compare tau load, measured by PET tau ligand
      uptake and cerebrospinal fluid (CSF) p-tau level, with a measure of genetic susceptibility to
      tau load, referred to as the genetic risk score for tau.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Tau Protein Uptake..
time frame: Day 1 - of 2 day study.
description: Whole brain mean (and standard deviation) cortical value derived from standardized uptake value ratio (SUVr). Each [F18]-T807 tau scan consisted of a 60-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-T807, followed by a second 20-minute dynamic imaging (list mode) acquisition from 80-100 minutes. SUVr images were constructed from the sum of the 80-100 minute frames resulting in late SUVr distribution maps.
measure: Beta-Amyloid (Aβ) Protein Uptake.
time frame: Day 2 - of 2 day study.
description: Mean and standard deviation for standardized uptake value ratios (SUVr) for posterior cingulate, superior parietal, lateral frontal, medial frontal, lateral temporal, and occipital brain regions. Each [F18]-Florbetapir (Beta-Amyloid) scan consisted of a 70-minute dynamic acquisition after bolus intravenous injection of 10 mCi of [18F]-Florbetapir. SUVr images were constructed from the sum of the 50-70 minute frames resulting in late SUVr distribution maps.
arm group label: Presumed CTE Group
arm group type: Experimental
description: Interventions administered to the Presumed CTE Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, MRI/MRS Scans, and Genetic Analysis for Genetic Risk Score for Tau.
arm group label: Control Group
arm group type: Experimental
description: Interventions administered to the Control Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, and MRI/MRS Scans.
arm group label: AD Dementia Group
arm group type: Experimental
description: Interventions administered to the AD Dementia Group include: [F-18]-T807 PET Scan, [F18]-Florbetapir PET Scan, MRI/MRS Scans
intervention type: Radiation
intervention name: [F18]-T807
description: [F18]-T807 PET Scan to measure tau deposition in the brain.
arm group label: AD Dementia Group
arm group label: Control Group
arm group label: Presumed CTE Group
other name: [F-18] AV-1451
intervention type: Radiation
intervention name: [F18]-Florbetapir
description: [F18]-Florbetapir PET scan to measure Beta-amyloid deposition in the brain.
arm group label: AD Dementia Group
arm group label: Control Group
arm group label: Presumed CTE Group
other name: Amyvid
intervention type: Device
intervention name: MRI/MRS
description: Two scans (structural, diffusion tensor imaging, and susceptibility weighted imaging scanned as part of one MR protocol, and a one-dimensional and two-dimensional spectroscopy examination as part of the other MR protocol.
arm group label: AD Dementia Group
arm group label: Control Group
arm group label: Presumed CTE Group
other name: Magnetic Resonance Imaging
other name: Magnetic Resonance Spectroscopy
other name: Diffusion Tensor Imaging
other name: Susceptibility Weighted Imgaging
other name: One-dimensional Spectroscopy
other name: Two-dimensional Spectroscopy
intervention type: Genetic
intervention name: Genetic Analysis for Genetic Risk Score for Tau.
description: DNA will be extracted from previously acquired and de-identified frozen blood specimens using a standard protocol (Gentra Puregene Kit, Qiagen 158422). Genotyping will be performed using the iPLEX Sequenom MassARRAY platform and samples will be genotyped for single nucleotide polymorphisms (SNPs) associated with the deposition of neurofibrillary tangles.
arm group label: Presumed CTE Group
criteria: 
gender: Male
minimum age: 40 Years
maximum age: 69 Years
healthy volunteers: No
last name: Martha E. Shenton, Ph.D.
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
facility: 
country: United States
citation: Zhang W, Arteaga J, Cashion DK, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Szardenings AK, Wang E, Walsh JC, Xia C, Yu C, Zhao T, Kolb HC. A highly selective and specific PET tracer for imaging of tau pathologies. J Alzheimers Dis. 2012;31(3):601-12. doi: 10.3233/JAD-2012-120712.
PMID: 22683529
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: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Martha E Shenton
investigator title: Director, Psychiatry Neuroimaging Laboratory
mesh term: Brain Diseases
mesh term: Brain Injuries, Traumatic
mesh term: Chronic Traumatic Encephalopathy
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Exploratory aims including potential MRI and MRS biomarkers and genetic analysis for genetic risk score for Tau will also be analyzed but are not primary or secondary outcome measures.
point of contact: 