<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/NCT03011983</url>
  </required_header>
  <id_info>
    <org_study_id>16-013207</org_study_id>
    <nct_id>NCT03011983</nct_id>
  </id_info>
  <brief_title>Neural Injury in Adolescents With Concussion</brief_title>
  <official_title>Neural Injury in Adolescents With Concussion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital of Philadelphia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study utilizes multimodal brain imaging to obtain quantitative biomarkers of brain&#xD;
      injury and to improve understanding of the biological basis of brain pathology in adolescents&#xD;
      with concussion. Adolescents with a concussion will undergo neuroimaging and neuropsychology&#xD;
      assessments acutely and four months after injury.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Concussion is a highly prevalent condition in adolescence, but it remains a clinical&#xD;
      diagnosis that largely relies on subjective patient report with no reliable objective&#xD;
      biomarkers for diagnosis. Traditional clinical brain imaging has not been found useful for&#xD;
      concussion as the pathology is generally not visible on conventional acute MRI or CT. The&#xD;
      proposed study addresses this gap in concussion diagnosis and management by examining the&#xD;
      sensitivity of magnetoencephalography (MEG) for identifying areas of brain injury through&#xD;
      detection of abnormal neural activity (slowing) in adolescents with concussion compared to&#xD;
      healthy controls. Adolescents with a concussion will complete neuroimaging (MEG and MRI) and&#xD;
      neuropsychology assessments at two time points within ten days and then again 4 months&#xD;
      post-injury. Healthy controls will complete neuroimaging and neuropsychology assessments at a&#xD;
      single time point.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 11, 2017</start_date>
  <completion_date type="Actual">June 1, 2018</completion_date>
  <primary_completion_date type="Actual">June 1, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in MEG Whole-Brain Slow-Wave Sensitivity between Controls and Concussion Patients</measure>
    <time_frame>Up to 2 months</time_frame>
    <description>Whole-brain, resting-state slow-wave maps of whole brain activity will be obtained from the MEG imaging in both adolescents with a concussion and healthy controls. Control images will be analyzed to determine a whole brain z-score value that includes typically developing controls below the 95th percentile, the z-score threshold for this group). Z-score images for the adolescents with concussion will be obtained and the number of adolescents with concussion above this z-score threshold will be determined, and compared to the healthy controls. The sensitivity and specificity of this method determined.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in MRI White-Matter Diffusion Measures between Controls and Concussion Patients</measure>
    <time_frame>Up to 2 months</time_frame>
    <description>MRI diffusion data will be collected to examine associations between abnormal brain slowing and white matter damage in the adolescents with a concussion versus controls. Regions showing abnormal white matter diffusion will be comparing to normative control diffusion data.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">4</enrollment>
  <condition>Mild Traumatic Brain Injury</condition>
  <condition>Concussion, Mild</condition>
  <condition>Acute Brain Injury</condition>
  <arm_group>
    <arm_group_label>Adolescents With Concussion</arm_group_label>
    <description>Adolescents with a concussion (n=120) will undergo neuroimaging (MEG and MRI) and neuropsychology assessments at two time points in the acute and chronic periods after injury, respectively. Brain imaging injury measures will be compared to a control normative database we will create. These brain measures will also be associated with cognitive and clinical outcomes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adolescents Without Concussion</arm_group_label>
    <description>Age- and gender-matched healthy controls (n=160) will be recruited to establish a normative database of whole-brain slow-wave maps from MEG resting-state data as well as white-matter diffusion measures from MRI.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MEG</intervention_name>
    <description>MEG is a non-invasive functional imaging technique that can measure slow-wave neural activity.</description>
    <arm_group_label>Adolescents With Concussion</arm_group_label>
    <arm_group_label>Adolescents Without Concussion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>MRI is a non-invasive imaging modality that provides measures of brain structure.</description>
    <arm_group_label>Adolescents With Concussion</arm_group_label>
    <arm_group_label>Adolescents Without Concussion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Neuropsychology assessment</intervention_name>
    <description>A battery of tests will be administered by a neuropsychologist to evaluate the cognitive function of adolescents with concussion compared to healthy controls.</description>
    <arm_group_label>Adolescents With Concussion</arm_group_label>
    <arm_group_label>Adolescents Without Concussion</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Adolescents with a recent concussion will be recruited from outpatient clinics in&#xD;
        orthopedics and trauma surgery. Healthy controls will be obtained via volunteers and&#xD;
        previous brain imaging research studies.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of concussion and within 2 weeks of injury (case subjects)&#xD;
&#xD;
          -  No history of diagnosed concussion (control subjects)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Head injury within 1 year of recent concussion (case subjects)&#xD;
&#xD;
          -  History of neurologic, psychiatric, developmental or learning disorders (all subjects)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christina L Master, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Philadelphia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Huang MX, Theilmann RJ, Robb A, Angeles A, Nichols S, Drake A, D'Andrea J, Levy M, Holland M, Song T, Ge S, Hwang E, Yoo K, Cui L, Baker DG, Trauner D, Coimbra R, Lee RR. Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients. J Neurotrauma. 2009 Aug;26(8):1213-26. doi: 10.1089/neu.2008.0672.</citation>
    <PMID>19385722</PMID>
  </reference>
  <reference>
    <citation>Huang MX, Nichols S, Robb A, Angeles A, Drake A, Holland M, Asmussen S, D'Andrea J, Chun W, Levy M, Cui L, Song T, Baker DG, Hammer P, McLay R, Theilmann RJ, Coimbra R, Diwakar M, Boyd C, Neff J, Liu TT, Webb-Murphy J, Farinpour R, Cheung C, Harrington DL, Heister D, Lee RR. An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes. Neuroimage. 2012 Jul 16;61(4):1067-82. doi: 10.1016/j.neuroimage.2012.04.029. Epub 2012 Apr 20.</citation>
    <PMID>22542638</PMID>
  </reference>
  <reference>
    <citation>Lewine JD, Davis JT, Bigler ED, Thoma R, Hill D, Funke M, Sloan JH, Hall S, Orrison WW. Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI. J Head Trauma Rehabil. 2007 May-Jun;22(3):141-55. doi: 10.1097/01.HTR.0000271115.29954.27.</citation>
    <PMID>17510590</PMID>
  </reference>
  <reference>
    <citation>Huang MX, Nichols S, Baker DG, Robb A, Angeles A, Yurgil KA, Drake A, Levy M, Song T, McLay R, Theilmann RJ, Diwakar M, Risbrough VB, Ji Z, Huang CW, Chang DG, Harrington DL, Muzzatti L, Canive JM, Christopher Edgar J, Chen YH, Lee RR. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury. Neuroimage Clin. 2014 Jun 16;5:109-19. doi: 10.1016/j.nicl.2014.06.004. eCollection 2014.</citation>
    <PMID>25009772</PMID>
  </reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>December 29, 2016</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>July 23, 2018</last_update_submitted>
  <last_update_submitted_qc>July 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Magnetoencephalography (MEG)</keyword>
  <keyword>Magnetic resonance imaging (MRI)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Brain Concussion</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_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/NCT03011983
org study id: 16-013207
nct id: NCT03011983
lead sponsor: 
has dmc: No
This study utilizes multimodal brain imaging to obtain quantitative biomarkers of brain
      injury and to improve understanding of the biological basis of brain pathology in adolescents
      with concussion. Adolescents with a concussion will undergo neuroimaging and neuropsychology
      assessments acutely and four months after injury.
Concussion is a highly prevalent condition in adolescence, but it remains a clinical
      diagnosis that largely relies on subjective patient report with no reliable objective
      biomarkers for diagnosis. Traditional clinical brain imaging has not been found useful for
      concussion as the pathology is generally not visible on conventional acute MRI or CT. The
      proposed study addresses this gap in concussion diagnosis and management by examining the
      sensitivity of magnetoencephalography (MEG) for identifying areas of brain injury through
      detection of abnormal neural activity (slowing) in adolescents with concussion compared to
      healthy controls. Adolescents with a concussion will complete neuroimaging (MEG and MRI) and
      neuropsychology assessments at two time points within ten days and then again 4 months
      post-injury. Healthy controls will complete neuroimaging and neuropsychology assessments at a
      single time point.
observational model: Case-Control
time perspective: Prospective
measure: Difference in MEG Whole-Brain Slow-Wave Sensitivity between Controls and Concussion Patients
time frame: Up to 2 months
description: Whole-brain, resting-state slow-wave maps of whole brain activity will be obtained from the MEG imaging in both adolescents with a concussion and healthy controls. Control images will be analyzed to determine a whole brain z-score value that includes typically developing controls below the 95th percentile, the z-score threshold for this group). Z-score images for the adolescents with concussion will be obtained and the number of adolescents with concussion above this z-score threshold will be determined, and compared to the healthy controls. The sensitivity and specificity of this method determined.
measure: Difference in MRI White-Matter Diffusion Measures between Controls and Concussion Patients
time frame: Up to 2 months
description: MRI diffusion data will be collected to examine associations between abnormal brain slowing and white matter damage in the adolescents with a concussion versus controls. Regions showing abnormal white matter diffusion will be comparing to normative control diffusion data.
arm group label: Adolescents With Concussion
description: Adolescents with a concussion (n=120) will undergo neuroimaging (MEG and MRI) and neuropsychology assessments at two time points in the acute and chronic periods after injury, respectively. Brain imaging injury measures will be compared to a control normative database we will create. These brain measures will also be associated with cognitive and clinical outcomes.
arm group label: Adolescents Without Concussion
description: Age- and gender-matched healthy controls (n=160) will be recruited to establish a normative database of whole-brain slow-wave maps from MEG resting-state data as well as white-matter diffusion measures from MRI.
intervention type: Device
intervention name: MEG
description: MEG is a non-invasive functional imaging technique that can measure slow-wave neural activity.
arm group label: Adolescents With Concussion
arm group label: Adolescents Without Concussion
intervention type: Device
intervention name: MRI
description: MRI is a non-invasive imaging modality that provides measures of brain structure.
arm group label: Adolescents With Concussion
arm group label: Adolescents Without Concussion
intervention type: Behavioral
intervention name: Neuropsychology assessment
description: A battery of tests will be administered by a neuropsychologist to evaluate the cognitive function of adolescents with concussion compared to healthy controls.
arm group label: Adolescents With Concussion
arm group label: Adolescents Without Concussion
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 12 Years
maximum age: 17 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Christina L Master, MD
role: Principal Investigator
affiliation: Children's Hospital of Philadelphia
facility: 
country: United States
citation: Huang MX, Theilmann RJ, Robb A, Angeles A, Nichols S, Drake A, D'Andrea J, Levy M, Holland M, Song T, Ge S, Hwang E, Yoo K, Cui L, Baker DG, Trauner D, Coimbra R, Lee RR. Integrated imaging approach with MEG and DTI to detect mild traumatic brain injury in military and civilian patients. J Neurotrauma. 2009 Aug;26(8):1213-26. doi: 10.1089/neu.2008.0672.
PMID: 19385722
citation: Huang MX, Nichols S, Robb A, Angeles A, Drake A, Holland M, Asmussen S, D'Andrea J, Chun W, Levy M, Cui L, Song T, Baker DG, Hammer P, McLay R, Theilmann RJ, Coimbra R, Diwakar M, Boyd C, Neff J, Liu TT, Webb-Murphy J, Farinpour R, Cheung C, Harrington DL, Heister D, Lee RR. An automatic MEG low-frequency source imaging approach for detecting injuries in mild and moderate TBI patients with blast and non-blast causes. Neuroimage. 2012 Jul 16;61(4):1067-82. doi: 10.1016/j.neuroimage.2012.04.029. Epub 2012 Apr 20.
PMID: 22542638
citation: Lewine JD, Davis JT, Bigler ED, Thoma R, Hill D, Funke M, Sloan JH, Hall S, Orrison WW. Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI. J Head Trauma Rehabil. 2007 May-Jun;22(3):141-55. doi: 10.1097/01.HTR.0000271115.29954.27.
PMID: 17510590
citation: Huang MX, Nichols S, Baker DG, Robb A, Angeles A, Yurgil KA, Drake A, Levy M, Song T, McLay R, Theilmann RJ, Diwakar M, Risbrough VB, Ji Z, Huang CW, Chang DG, Harrington DL, Muzzatti L, Canive JM, Christopher Edgar J, Chen YH, Lee RR. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury. Neuroimage Clin. 2014 Jun 16;5:109-19. doi: 10.1016/j.nicl.2014.06.004. eCollection 2014.
PMID: 25009772
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Brain Concussion
mesh term: Wounds and Injuries
sharing ipd: No