xml: <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/NCT06031662</url>
    </required_header>
    <id_info>
      <org_study_id>5821</org_study_id>
      <nct_id>NCT06031662</nct_id>
    </id_info>
    <brief_title>Accelerated, Theta-burst Stimulation for the Treatment of Post-concussion Syndrome</brief_title>
    <official_title>Image-guided, Accelerated, Theta-burst Stimulation for the Treatment of Post-concussion Syndrome</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sunnybrook Health Sciences Centre</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Sunnybrook Health Sciences Centre</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        TMS has been safely and reliably delivered at the Harquail Centre for over 5 years, with a&#xD;
        primary focus on conventional rTMS protocols for treatment-resistant depression. Recently,&#xD;
        the investgator team has gained the capability to deliver sham-controlled intermittent&#xD;
        theta-burst stimulation (iTBS) rTMS. Unlike conventional high frequency rTMS, which was used&#xD;
        in the previous sham-controlled rTMS PCS pilot study, iTBS is a patterned form of stimulation&#xD;
        that recapitulates endogenous activity patterns of neural circuits pairing gamma frequency&#xD;
        (50Hz) burst pulses coupled in a theta frequency rhythm (5Hz).12 iTBS delivers 600 pulses in&#xD;
        just over 3 minutes with similar or greater effects on neural plasticity compared to&#xD;
        conventional rTMS (taking over 30-45 minutes) and similar tolerability and efficacy in trials&#xD;
        of depression. Furthermore, novel accelerated iTBS protocols stimulating the left&#xD;
        dorsolateral prefrontal cortex (dlPFC) over 8-10 treatments, 50 minutes apart over a 5 day&#xD;
        interval has recently demonstrated robust efficacy in depression and received recent FDA&#xD;
        approval. Thus, accelerated iTBS can be delivered in a single week of treatment compared to 6&#xD;
        weeks with conventional rTMS methods. Finally, the investigators recently acquired the&#xD;
        technology to integrate MRI neuroimage-guided stimulation, which would allow to target&#xD;
        specific brain regions/networks implicated in PCS at high spatial resolution. No studies to&#xD;
        date have investigated image-guided accelerated iTBS rTMS for the treatment of PCS.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">August 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 1, 2025</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>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Participant)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Rivermead Post Concussion Symptoms Questionnaire</measure>
      <time_frame>Baseline, change from baseline to immediately before the first iTBS treatment</time_frame>
      <description>RPQ, a validated measure of subjective global PCS symptoms.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Rivermead Post Concussion Symptoms Questionnaire</measure>
      <time_frame>5 days</time_frame>
      <description>RPQ, a validated measure of subjective global PCS symptoms.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Rivermead Post Concussion Symptoms Questionnaire</measure>
      <time_frame>1 month post-treatment</time_frame>
      <description>RPQ, a validated measure of subjective global PCS symptoms.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Montgomery-Åsberg Depression Rating Scale</measure>
      <time_frame>Baseline, post treatment day 5, and post treatment 1 month</time_frame>
      <description>Montgomery-Åsberg Depression Rating Scale is a widely used clinician-rated measure of depressive severity</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Repeatable Battery for the Assessment of Neuropsychological Status</measure>
      <time_frame>Baseline and post treatment 1 month</time_frame>
      <description>RBANS is a brief, individually administered battery to measure cognitive decline or improvement</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The Behavior Rating Inventory of Executive Function</measure>
      <time_frame>Baseline, post treatment day 5, and post treatment 1 month</time_frame>
      <description>BRIEF-A is a standardized measure that captures views of an adult's executive functions or self-regulation in his or her everyday environment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Headache Impact Test</measure>
      <time_frame>Baseline and post treatment 1 month</time_frame>
      <description>HIT is a tool used to measure the impact headaches have on your ability to function on the job, at school, at home and in social situations.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">26</enrollment>
    <condition>Post Concussion Syndrome</condition>
    <arm_group>
      <arm_group_label>Treatment</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Intermittent Theta-Burst Stimulation</intervention_name>
      <description>Accelerated course of left dlPFC iTBS, consisting of 600 pulses/session, 50 minutes intersession interval, 8 session/day for 5 days) at 90% resting MT</description>
      <arm_group_label>Treatment</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Sham Intermittent Theta-Burst Stimulation</intervention_name>
      <description>Magventure Active/Placebo B70 coil specifically designed for randomized clinical trials with TMS. This system uses electrodes placed on the scalp to provide stimulation mimicking the active treatment condition</description>
      <arm_group_label>Sham</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Documented evidence of head trauma sufficiently severe to result in loss of&#xD;
               consciousness, post-traumatic amnesia and/or acute altered mental status.&#xD;
  &#xD;
            -  At least three symptoms including headache, dizziness, fatigue, irritability,&#xD;
               insomnia, memory difficulties, concentration difficulties, mood dysregulation.&#xD;
  &#xD;
            -  Onset of symptoms within 4 weeks following the head trauma.&#xD;
  &#xD;
            -  Age 18-60, inclusive.&#xD;
  &#xD;
            -  Persistence of PCS symptoms for at least 3 months but less than 12 months&#xD;
  &#xD;
            -  Able to provide informed consent and comply with the study protocol&#xD;
  &#xD;
            -  Patients will not be excluded solely on the basis of communication (i.e., non-English&#xD;
               speaking) unless they have exclusion criteria that is the cause of the communication&#xD;
               difficulties.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Evidence of major structural neuroimaging abnormalities (e.g., intracranial&#xD;
               hemorrhage, skull fracture or a large intracranial lesion)&#xD;
  &#xD;
            -  History of prior rTMS therapy,&#xD;
  &#xD;
            -  Contraindications to MRI (e.g., pacemaker, metallic implants etc.).&#xD;
  &#xD;
            -  Ferromagnetic, non-removable metallic implants from above the clavicle with the&#xD;
               exception of dental work.&#xD;
  &#xD;
            -  Active personal injury litigation&#xD;
  &#xD;
            -  History of seizure disorder, not including febrile seizures in childhood&#xD;
  &#xD;
            -  Substance dependence within the last 6 months&#xD;
  &#xD;
            -  Pregnant&#xD;
  &#xD;
            -  Currently taking more than lorazepam 2 mg daily (or benzodiazepine equivalent) or any&#xD;
               dose of an anticonvulsant (due to the potential to reduce rTMS efficacy)&#xD;
  &#xD;
            -  Currently taking an antiepileptic medication&#xD;
  &#xD;
            -  Mild and major comorbid medical conditions (as determined by investigators - e.g.,&#xD;
               neurological diseases, uncontrolled hypertension or diabetes, malignancy)&#xD;
  &#xD;
            -  A major comorbid psychiatric disorder (as determined by investigators - e.g.,&#xD;
               schizophrenia or bipolar disorder) and/or psychosis at the time of study enrollment&#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_contact>
      <last_name>Sean Nestor, PhD, MD, FRCPC</last_name>
      <phone>416-480-4085</phone>
      <email>sean.nestor@sunnybrook.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Matthew Burke, MD, FRCPC</last_name>
      <phone>416-480-4216</phone>
      <email>matthew.burke@sunnybrook.ca</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>June 20, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Sunnybrook Health Sciences Centre</investigator_affiliation>
      <investigator_full_name>Dr. Sean Michael Nestor</investigator_full_name>
      <investigator_title>clinician-investigator and interventional psychiatrist</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Post-Concussion Syndrome</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06031662
  org study id: 5821
  nct id: NCT06031662
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  TMS has been safely and reliably delivered at the Harquail Centre for over 5 years, with a
        primary focus on conventional rTMS protocols for treatment-resistant depression. Recently,
        the investgator team has gained the capability to deliver sham-controlled intermittent
        theta-burst stimulation (iTBS) rTMS. Unlike conventional high frequency rTMS, which was used
        in the previous sham-controlled rTMS PCS pilot study, iTBS is a patterned form of stimulation
        that recapitulates endogenous activity patterns of neural circuits pairing gamma frequency
        (50Hz) burst pulses coupled in a theta frequency rhythm (5Hz).12 iTBS delivers 600 pulses in
        just over 3 minutes with similar or greater effects on neural plasticity compared to
        conventional rTMS (taking over 30-45 minutes) and similar tolerability and efficacy in trials
        of depression. Furthermore, novel accelerated iTBS protocols stimulating the left
        dorsolateral prefrontal cortex (dlPFC) over 8-10 treatments, 50 minutes apart over a 5 day
        interval has recently demonstrated robust efficacy in depression and received recent FDA
        approval. Thus, accelerated iTBS can be delivered in a single week of treatment compared to 6
        weeks with conventional rTMS methods. Finally, the investigators recently acquired the
        technology to integrate MRI neuroimage-guided stimulation, which would allow to target
        specific brain regions/networks implicated in PCS at high spatial resolution. No studies to
        date have investigated image-guided accelerated iTBS rTMS for the treatment of PCS.
  allocation: Randomized
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: Single (Participant)
  measure: Rivermead Post Concussion Symptoms Questionnaire
  time frame: Baseline, change from baseline to immediately before the first iTBS treatment
  description: RPQ, a validated measure of subjective global PCS symptoms.
  measure: Rivermead Post Concussion Symptoms Questionnaire
  time frame: 5 days
  description: RPQ, a validated measure of subjective global PCS symptoms.
  measure: Rivermead Post Concussion Symptoms Questionnaire
  time frame: 1 month post-treatment
  description: RPQ, a validated measure of subjective global PCS symptoms.
  measure: Montgomery-Åsberg Depression Rating Scale
  time frame: Baseline, post treatment day 5, and post treatment 1 month
  description: Montgomery-Åsberg Depression Rating Scale is a widely used clinician-rated measure of depressive severity
  measure: Repeatable Battery for the Assessment of Neuropsychological Status
  time frame: Baseline and post treatment 1 month
  description: RBANS is a brief, individually administered battery to measure cognitive decline or improvement
  measure: The Behavior Rating Inventory of Executive Function
  time frame: Baseline, post treatment day 5, and post treatment 1 month
  description: BRIEF-A is a standardized measure that captures views of an adult's executive functions or self-regulation in his or her everyday environment.
  measure: Headache Impact Test
  time frame: Baseline and post treatment 1 month
  description: HIT is a tool used to measure the impact headaches have on your ability to function on the job, at school, at home and in social situations.
  arm group label: Treatment
  arm group type: Experimental
  arm group label: Sham
  arm group type: Sham Comparator
  intervention type: Device
  intervention name: Intermittent Theta-Burst Stimulation
  description: Accelerated course of left dlPFC iTBS, consisting of 600 pulses/session, 50 minutes intersession interval, 8 session/day for 5 days) at 90% resting MT
  arm group label: Treatment
  intervention type: Device
  intervention name: Sham Intermittent Theta-Burst Stimulation
  description: Magventure Active/Placebo B70 coil specifically designed for randomized clinical trials with TMS. This system uses electrodes placed on the scalp to provide stimulation mimicking the active treatment condition
  arm group label: Sham
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: No
  last name: Sean Nestor, PhD, MD, FRCPC
  phone: 416-480-4085
  email: sean.nestor@sunnybrook.ca
  last name: Matthew Burke, MD, FRCPC
  phone: 416-480-4216
  email: matthew.burke@sunnybrook.ca
  responsible party type: Principal Investigator
  investigator affiliation: Sunnybrook Health Sciences Centre
  investigator full name: Dr. Sean Michael Nestor
  investigator title: clinician-investigator and interventional psychiatrist
  mesh term: Post-Concussion Syndrome
  mesh term: Syndrome
  sharing ipd: No