<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/NCT03819608</url>
  </required_header>
  <id_info>
    <org_study_id>1034818</org_study_id>
    <nct_id>NCT03819608</nct_id>
  </id_info>
  <brief_title>Neuromodulation and Neurorehabilitation for mTBI Plus PTSD</brief_title>
  <official_title>Neuromodulation and Neurorehabilitation for Treatment of Functional Deficits After mTBI and PTSD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Theresa Pape</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Edward Hines Jr. VA Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will determine (i) the magnitude of immediate and sustained effects of a current&#xD;
      clinical standard interactive computer attention processing training (APT) when combined with&#xD;
      intermittent theta burst stimulation (iTBS), a type of repetitive transcranial magnetic&#xD;
      stimulation and (ii) determine how APT + iTBS changes the neurocognitive system of attention&#xD;
      in individuals with persistent attention deficits related to mTBI and PTSD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Anticipated">October 2020</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">March 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the Mayo Portland Adaptability Inventory (MPAI)</measure>
    <time_frame>baseline, 5 weeks, 10 weeks, 20 weeks</time_frame>
    <description>Self-reported ability, adjustment and community participation. It is comprised of 30 items and three subscales: Ability Index, Adjustment Index and Participation Index. Items are scored on a 5-point Likert scale, with lower scores indicating higher levels of functioning.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>change in the PTSD Checklist (PCL)</measure>
    <time_frame>baseline, 5 weeks, 10 weeks, 20 weeks</time_frame>
    <description>20-item self-report measure assessing the distress associated with PTSD symptoms. The higher the score, the worse the symptoms.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Mild Traumatic Brain Injury</condition>
  <condition>Post Traumatic Stress Disorder</condition>
  <arm_group>
    <arm_group_label>real APT+ real iTBS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>real APT+ real iTBS included 30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. APT-III is a computer based cognitive training program. iTMS will be applied at 5Hz rate; each burst consists of 3 pulses delivered at 50Hz rate. The bursts are applied for 2s with 8s inter-burst-intervals, for a total of 600 pulses. The total stimulation time per session is approximately 192s (~ 3 minutes). Participants randomized to active iTBS will receive stimulation at the right dorsolateral prefrontal cortex at 80% active motor threshold .</description>
  </arm_group>
  <arm_group>
    <arm_group_label>real APT + placebo iTBS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. APT-III is a computer based cognitive training program. Participants randomized to placebo iTBS will not receive any iTBS stimulation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo APT+ real iTBS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. Placebo APT-III is a computer based active control cognitive training program. Bursts of TMS pulses will be applied at 5Hz rate; each burst consists of 3 pulses delivered at 50Hz rate. The bursts are applied for 2s with 8s inter-burst-intervals, for a total of 600 pulses. The total stimulation time per session is approximately 192s (~ 3 minutes). Participants randomized to active iTBS will receive stimulation at the right DLPFC at 80% active motor threshold .</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo APT+ placebo iTBS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. Placebo APT-III is a computer based active control cognitive training program. Participants randomized to placebo iTBS will not receive any iTBS stimulation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>real iTBS</intervention_name>
    <description>Intermittent Theta Burst Stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (rTMS), which uses short magnetic field pulses applied to the scalp to induce currents in the underlying brain. iTBS will be delivered with the Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P. The Magpro Cool Coil B65 A/P can be switched to active or placebo (A/P).</description>
    <arm_group_label>placebo APT+ real iTBS</arm_group_label>
    <arm_group_label>real APT+ real iTBS</arm_group_label>
    <other_name>intermittent Theta Burst Stimulation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>real APT</intervention_name>
    <description>APT-III is an attention processing training program</description>
    <arm_group_label>real APT + placebo iTBS</arm_group_label>
    <arm_group_label>real APT+ real iTBS</arm_group_label>
    <other_name>Attention Processing Training-III</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>placebo APT</intervention_name>
    <description>computerized cognitive training</description>
    <arm_group_label>placebo APT+ placebo iTBS</arm_group_label>
    <arm_group_label>placebo APT+ real iTBS</arm_group_label>
    <other_name>Active Control APT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>placebo iTBS</intervention_name>
    <description>delivered with the Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P. The Magpro Cool Coil B65 A/P can be switched to active or placebo (A/P).</description>
    <arm_group_label>placebo APT+ placebo iTBS</arm_group_label>
    <arm_group_label>real APT + placebo iTBS</arm_group_label>
    <other_name>sham intermittent Theta Burst Stimulation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least 18 years of age and no older than 60 years of age&#xD;
&#xD;
          -  3 months to 10 years post exposure to mTBI event&#xD;
&#xD;
          -  Have co-occurring mTBI and PTSD as defined by the Symptom Attribution and&#xD;
             Classification Algorithm (SACA) and the Clinically Administered PTSD Scale for DSM-V&#xD;
             (CAPS-5)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participating in another research study&#xD;
&#xD;
          -  Non-fluent in English (speaking and reading)&#xD;
&#xD;
          -  History of epilepsy pre-injury&#xD;
&#xD;
          -  Receiving antiepileptic treatment for documented active seizures in the past 6 months&#xD;
&#xD;
          -  Taking medications that lower seizure threshold including antipsychotics, buproprion,&#xD;
             trazodone and tramadol&#xD;
&#xD;
          -  History of surgery on blood vessels in brain and/or valves of the heart&#xD;
&#xD;
          -  History of brain hemorrhage, neurovascular conditions and neurodegenerative disorders&#xD;
&#xD;
          -  History or current diagnosis of psychotic spectrum disorders (i.e. bipolar,&#xD;
             schizophrenia)&#xD;
&#xD;
          -  Significant heart disease as determined by physician review of medical chart&#xD;
&#xD;
          -  Pregnant at time of enrollment or any time during study participation&#xD;
&#xD;
          -  MRI or TMS/iTBS contraindications such as claustrophobia, metal in eyes/face or brain&#xD;
&#xD;
          -  Cardiac pacemakers/defibrillators, cochlear implants, nerve stimulators, intracranial&#xD;
             metal clips&#xD;
&#xD;
          -  Diagnosis of moderate or severe TBI (loss of consciousness &gt; 30 minutes, alteration of&#xD;
             consciousness &gt; 24 hours, post traumatic amnesia or neuropsychological testing results&#xD;
&#xD;
          -  Mental health medications have been altered within the month preceding study screening&#xD;
&#xD;
          -  Taking prescribed CNS stimulants and choosing to not stop these medications during&#xD;
             study participation&#xD;
&#xD;
          -  Testing positive for opiates and do not have a prescription for opiates. If on&#xD;
             prescription opiates and taking more than the equivalent of 200 mg of morphine per&#xD;
             day.&#xD;
&#xD;
          -  Taking tricyclic antidepressants&#xD;
&#xD;
          -  Questionably valid test performance as indicated by a score of ≤ 85% on the Immediate&#xD;
             Recognition, Delayed Recognition or Consistency Scales of the Medical Symptom Validity&#xD;
             Test (MSVT) and clinical determination of questionable performance validity by a&#xD;
             neuropsychologist on the research team&#xD;
&#xD;
          -  Actively suicidal as evidenced by plan to harm or recent attempt communicated on the&#xD;
             Structured Clinical Interview for DSM-V (SCID-5).&#xD;
&#xD;
          -  Increased Intracranial Pressure (ICP) as evidenced through a funduscopic evaluation or&#xD;
             on the baseline MRI scan.&#xD;
&#xD;
          -  Moderate or severe cannabis use disorder defined by ≥ 4 symptoms on the SCID-5&#xD;
&#xD;
          -  Severe alcohol use disorder defined by ≥ 4 symptoms on the SCID-5&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Theresa LB Pape, Dr.PH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Edward Hines Jr. VA Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Catherine M Kestner</last_name>
    <phone>708-878-0578</phone>
    <email>Catherine.Kestner@va.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ann Guernon, MS</last_name>
    <phone>708-202-8387</phone>
    <phone_ext>114</phone_ext>
    <email>ann.guernon@va.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60141</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ann Guernon, MS, CCC-SLP, CCRC</last_name>
      <phone>708-2028387</phone>
      <phone_ext>23114</phone_ext>
      <email>ComaResearch@va.gov</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Edward Hines, Jr. VA Hospital</name>
      <address>
        <city>Hines</city>
        <state>Illinois</state>
        <zip>60141</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Theresa Pape, DrPH</last_name>
      <phone>708-202-4953</phone>
      <email>ComaResearch@va.gov</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>January 15, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>August 13, 2020</last_update_submitted>
  <last_update_submitted_qc>August 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Edward Hines Jr. VA Hospital</investigator_affiliation>
    <investigator_full_name>Theresa Pape</investigator_full_name>
    <investigator_title>Research Health Scientist</investigator_title>
  </responsible_party>
  <keyword>mTBI</keyword>
  <keyword>PTSD</keyword>
  <keyword>intermittent theta burst stimulation</keyword>
  <keyword>cognitive training</keyword>
  <keyword>neuroimaging</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>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>FITBIR</ipd_description>
  </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/NCT03819608
org study id: 1034818
nct id: NCT03819608
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
This study will determine (i) the magnitude of immediate and sustained effects of a current
      clinical standard interactive computer attention processing training (APT) when combined with
      intermittent theta burst stimulation (iTBS), a type of repetitive transcranial magnetic
      stimulation and (ii) determine how APT + iTBS changes the neurocognitive system of attention
      in individuals with persistent attention deficits related to mTBI and PTSD.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in the Mayo Portland Adaptability Inventory (MPAI)
time frame: baseline, 5 weeks, 10 weeks, 20 weeks
description: Self-reported ability, adjustment and community participation. It is comprised of 30 items and three subscales: Ability Index, Adjustment Index and Participation Index. Items are scored on a 5-point Likert scale, with lower scores indicating higher levels of functioning.
measure: change in the PTSD Checklist (PCL)
time frame: baseline, 5 weeks, 10 weeks, 20 weeks
description: 20-item self-report measure assessing the distress associated with PTSD symptoms. The higher the score, the worse the symptoms.
arm group label: real APT+ real iTBS
arm group type: Experimental
description: real APT+ real iTBS included 30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. APT-III is a computer based cognitive training program. iTMS will be applied at 5Hz rate; each burst consists of 3 pulses delivered at 50Hz rate. The bursts are applied for 2s with 8s inter-burst-intervals, for a total of 600 pulses. The total stimulation time per session is approximately 192s (~ 3 minutes). Participants randomized to active iTBS will receive stimulation at the right dorsolateral prefrontal cortex at 80% active motor threshold .
arm group label: real APT + placebo iTBS
arm group type: Active Comparator
description: 30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. APT-III is a computer based cognitive training program. Participants randomized to placebo iTBS will not receive any iTBS stimulation.
arm group label: placebo APT+ real iTBS
arm group type: Active Comparator
description: 30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. Placebo APT-III is a computer based active control cognitive training program. Bursts of TMS pulses will be applied at 5Hz rate; each burst consists of 3 pulses delivered at 50Hz rate. The bursts are applied for 2s with 8s inter-burst-intervals, for a total of 600 pulses. The total stimulation time per session is approximately 192s (~ 3 minutes). Participants randomized to active iTBS will receive stimulation at the right DLPFC at 80% active motor threshold .
arm group label: placebo APT+ placebo iTBS
arm group type: Active Comparator
description: 30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. Placebo APT-III is a computer based active control cognitive training program. Participants randomized to placebo iTBS will not receive any iTBS stimulation.
intervention type: Device
intervention name: real iTBS
description: Intermittent Theta Burst Stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (rTMS), which uses short magnetic field pulses applied to the scalp to induce currents in the underlying brain. iTBS will be delivered with the Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P. The Magpro Cool Coil B65 A/P can be switched to active or placebo (A/P).
arm group label: placebo APT+ real iTBS
arm group label: real APT+ real iTBS
other name: intermittent Theta Burst Stimulation
intervention type: Behavioral
intervention name: real APT
description: APT-III is an attention processing training program
arm group label: real APT + placebo iTBS
arm group label: real APT+ real iTBS
other name: Attention Processing Training-III
intervention type: Behavioral
intervention name: placebo APT
description: computerized cognitive training
arm group label: placebo APT+ placebo iTBS
arm group label: placebo APT+ real iTBS
other name: Active Control APT
intervention type: Device
intervention name: placebo iTBS
description: delivered with the Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P. The Magpro Cool Coil B65 A/P can be switched to active or placebo (A/P).
arm group label: placebo APT+ placebo iTBS
arm group label: real APT + placebo iTBS
other name: sham intermittent Theta Burst Stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Theresa LB Pape, Dr.PH
role: Principal Investigator
affiliation: Edward Hines Jr. VA Hospital
last name: Catherine M Kestner
phone: 708-878-0578
email: Catherine.Kestner@va.gov
last name: Ann Guernon, MS
phone: 708-202-8387
phone ext: 114
email: ann.guernon@va.gov
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Edward Hines Jr. VA Hospital
investigator full name: Theresa Pape
investigator title: Research Health Scientist
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Brain Concussion
mesh term: Stress Disorders, Traumatic
mesh term: Stress Disorders, Post-Traumatic
sharing ipd: Yes
ipd description: FITBIR