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/NCT05983211</url>
    </required_header>
    <id_info>
      <org_study_id>QuARTS ALS</org_study_id>
      <nct_id>NCT05983211</nct_id>
    </id_info>
    <brief_title>Quantitative and Repetitive TMS in ALS</brief_title>
    <acronym>QuARTS-ALS</acronym>
    <official_title>A Biomarker-Directed Neuromodulation Trial Using Quantitative and Repetitive Transcranial Magnetic Stimulation in Amyotrophic Lateral Sclerosis (The QuARTS-ALS Trial)</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>
        The goal of this open-label pilot clinical trial is to evaluate the safety, tolerability and&#xD;
        target engagement of accelerated, high dose continuous theta-burst stimulation (cTBS) using&#xD;
        transcranial magnetic stimulation (TMS) in patients with ALS.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The purpose of this study is to:&#xD;
  &#xD;
          1. Evaluate the safety and feasibility of cTBS neuromodulation with repetitive TMS&#xD;
             treatment using an accelerated schedule in patients with ALS.&#xD;
  &#xD;
          2. Assess the changes in corticospinal excitability using quantitative single- and&#xD;
             paired-pulse TMS measures.&#xD;
  &#xD;
          3. Assess the changes in MR spectroscopy of glutamate and GABA spectra after cTBS&#xD;
             neuromodulation.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 1, 2023</start_date>
    <completion_date type="Anticipated">April 15, 2026</completion_date>
    <primary_completion_date type="Anticipated">April 15, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>A prospective, single-arm, open-label pilot trial evaluating the safety, feasibility and changes in corticospinal excitability biomarkers after accelerated repetitive transcranial magnetic stimulation (rTMS) using continuous theta burst stimulation (cTBS) inhibitory paradigms over the primary motor cortex (M1) in patients with ALS.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Safety and Feasibility of cTBS rTMS in patients with ALS</measure>
      <time_frame>One Week before and after cTBS treatment</time_frame>
      <description>Incidence of AEs and SAEs after accelerated continuous theta burst stimulation inhibitory intervention in individuals with ALS through the incidence of repetitive TMS treatment related adverse events, serious adverse events, discontinuations due to adverse events/serious adverse events, or accelerated ALS disease progression as defined by ≥6-point decline in the ALSFRS-R scores.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Corticospinal Excitability change measured by TMS Resting Motor Threshold</measure>
      <time_frame>One and Three Weeks after cTBS treatment</time_frame>
      <description>Change from baseline in Resting Motor Threshold (RMT)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Corticospinal Excitability change measured by TMS Short Intracortical Inhibition</measure>
      <time_frame>One and Three Weeks after cTBS treatment</time_frame>
      <description>Change from baseline in Short Intracortical Inhibition (SICI)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Corticospinal Excitability change measured by TMS Short Intracortical Facilitation</measure>
      <time_frame>One and Three Weeks after cTBS treatment</time_frame>
      <description>Change from baseline in Short Intracortical Facilitation (SICF)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Corticospinal Excitability change measured by TMS Cortical Silent Period</measure>
      <time_frame>One and Three Weeks after cTBS treatment</time_frame>
      <description>Change from baseline in Cortical Silent Period (CSP)</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Magnetic Resonance Spectroscopy parameters as measured by 1H-MRS</measure>
      <time_frame>One Week after cTBS treatment</time_frame>
      <description>Change from baseline in Glutamate/GABA ratio</description>
    </other_outcome>
    <other_outcome>
      <measure>Neurofilament-light chain levels</measure>
      <time_frame>Three Weeks after cTBS treatment</time_frame>
      <description>Change from baseline in concentration of serum neurofilament light chain</description>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">15</enrollment>
    <condition>Amyotrophic Lateral Sclerosis</condition>
    <arm_group>
      <arm_group_label>Accelerated cTBS Neuromodulation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>ALS patients receiving an accelerated schedule of continuous theta burst rTMS at a regimen of 40 seconds per treatment, for 5-6 treatment sessions per day, delivered one per hour, over 5 days (up to possible total 30 treatments).</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Repetitive Transcranial Magnetic Stimulation</intervention_name>
      <description>Accelerated rTMS using continuous theta burst stimulation inhibitory paradigms over unilateral M1 hand region outputted at 90% of resting motor threshold, using bursts of 3 pulses at 50 Hz. Bursts are repeated at 5 Hz for a total of 600 pulses over 40 seconds. ALS patients will receive rTMS at a regimen of cTBS for 40 seconds per treatment, for 5-6 treatment sessions per day, delivered one per hour, over 5 days (up to possible total 30 treatments).</description>
      <arm_group_label>Accelerated cTBS Neuromodulation</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis with ALS as per the 2020 Gold Coast Criteria;&#xD;
  &#xD;
            -  Age ≥ 18 years;&#xD;
  &#xD;
            -  Able to provide informed consent to study procedures and treatments;&#xD;
  &#xD;
            -  If taking Riluzole, must be on a stable dose for at least 12 weeks prior to Baseline;&#xD;
  &#xD;
            -  If undergoing Edaravone treatment, must be on a stable dose of at least one completed&#xD;
               cycle (IV or Oral Edaravone) prior to Baseline;&#xD;
  &#xD;
            -  If taking AMX005, must be on stable dose for at least 4 weeks prior to Baseline;&#xD;
  &#xD;
            -  Manual muscle testing with MRC score ≥4- AND nerve conduction study CMAP amplitude&#xD;
               ≥1.0mV in the first dorsi interosseous (FDI) on at least one side;&#xD;
  &#xD;
            -  Able to tolerate TMS procedures;&#xD;
  &#xD;
            -  Able to lie supine without BiPAP or breathing discomfort for at least 1 hour;&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Known diagnosis of dementia;&#xD;
  &#xD;
            -  Definitely or possibly pregnant (if applicable);&#xD;
  &#xD;
            -  History of allergy to Ag-AgCl electrode gel (standard neurophysiology electrodes);&#xD;
  &#xD;
            -  Any contraindications to TMS as follow:&#xD;
  &#xD;
            -  Metal implants in the head or neck (such as aneurysm clips, vessel stents), implanted&#xD;
               medication pump, implanted brain stimulators, pacemaker, cochlear implants, or history&#xD;
               of epilepsy. Dental fillings are permitted;&#xD;
  &#xD;
            -  Current use of an antipsychotic or antiarrhythmic medication;&#xD;
  &#xD;
            -  On medications that affect TMS measures in a PRN regimen (as needed). Continuous use&#xD;
               of these medications on a fixed dose of 30 days prior to first Baseline Visit or after&#xD;
               a wash-out period of 2 weeks is accepted. These medications include: benzodiazepines,&#xD;
               muscle relaxants, tricyclic antidepressants, selective and non-selective serotonin&#xD;
               reuptake inhibitors, hypnotics (including anti-histamine drugs) and anticholinergics&#xD;
               drugs;&#xD;
  &#xD;
            -  History of seizure, convulsion, or epilepsy;&#xD;
  &#xD;
            -  Any contraindications to MRI such as:&#xD;
  &#xD;
            -  Large body habitus and not fitting comfortably into the scanner;&#xD;
  &#xD;
            -  Difficulty laying still for up to 1 hour in the MRI unit or significant&#xD;
               claustrophobia;&#xD;
  &#xD;
            -  Metallic implants;&#xD;
  &#xD;
            -  Any contraindications for receiving rTMS treatment as follow:&#xD;
  &#xD;
            -  have received rTMS for any previous indication due to the potential compromise of&#xD;
               subject blinding;&#xD;
  &#xD;
            -  have increased intracranial pressure, a space occupying brain lesion, any history of&#xD;
               seizure except those therapeutically induced by ECT or a febrile seizure of infancy,&#xD;
               significant head trauma with clear radiological evidence of cerebrovascular injury on&#xD;
               imaging;&#xD;
  &#xD;
            -  have an intracranial implant or any other metal object within or near the head,&#xD;
               excluding the mouth, that cannot be safely removed;&#xD;
  &#xD;
            -  have clinically significant laboratory abnormality, in the opinion of the one of the&#xD;
               principal investigators or study physicians;&#xD;
  &#xD;
            -  are currently taking more than lorazepam 2 mg daily (or equivalent) or any dose of an&#xD;
               anticonvulsant due to the potential to limit rTMS efficacy;&#xD;
  &#xD;
            -  Any other clinical condition that, in the opinion of the Site Investigator, would&#xD;
               place the subject at increased risk or preclude the subject's full compliance with&#xD;
               completion of the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Agessandro Abrahao, Dr.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sunnybrook Health Sciences Centre; University of Toronto</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Lorne Zinman, Dr.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sunnybrook Health Sciences Centre; University of Toronto</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Sean Nestor, Dr.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sunnybrook Research Institute; University of Toronto</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Agessandro Abrahao, Dr.</last_name>
      <phone>(416) 480-6100</phone>
      <phone_ext>87561</phone_ext>
      <email>alsresearch@sunnybrook.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jahan Mookshah</last_name>
      <phone>416 480-6100</phone>
      <phone_ext>87561</phone_ext>
      <email>jahan.mookshah@sunnybrook.ca</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Sunnybrook Health Sciences Centre</name>
        <address>
          <city>Toronto</city>
          <state>Ontario</state>
          <zip>M4N 3M5</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Agessandro Abrahao, Dr</last_name>
        <phone>(416) 480-6100</phone>
        <phone_ext>87561</phone_ext>
        <email>alsresearch@sunnybrook.ca</email>
      </contact>
      <contact_backup>
        <last_name>Jahan Mookshah</last_name>
        <phone>(416) 480-6100</phone>
        <phone_ext>87561</phone_ext>
        <email>jahan.mookshah@sunnybrook.ca</email>
      </contact_backup>
      <investigator>
        <last_name>Agessandro Abrahao, Dr</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Lorne Zinman, Dr</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Sean Nestor, Dr</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>ALS</keyword>
    <keyword>Repetitive transcranial magnetic stimulation</keyword>
    <keyword>Corticospinal Excitability</keyword>
    <keyword>Motor Neuron Disease</keyword>
    <keyword>MR Spectroscopy</keyword>
    <keyword>Cortical Hyperexcitability</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Motor Neuron Disease</mesh_term>
      <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
      <mesh_term>Sclerosis</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/NCT05983211
  org study id: QuARTS ALS
  nct id: NCT05983211
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this open-label pilot clinical trial is to evaluate the safety, tolerability and
        target engagement of accelerated, high dose continuous theta-burst stimulation (cTBS) using
        transcranial magnetic stimulation (TMS) in patients with ALS.
  The purpose of this study is to:
  
          1. Evaluate the safety and feasibility of cTBS neuromodulation with repetitive TMS
             treatment using an accelerated schedule in patients with ALS.
  
          2. Assess the changes in corticospinal excitability using quantitative single- and
             paired-pulse TMS measures.
  
          3. Assess the changes in MR spectroscopy of glutamate and GABA spectra after cTBS
             neuromodulation.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: A prospective, single-arm, open-label pilot trial evaluating the safety, feasibility and changes in corticospinal excitability biomarkers after accelerated repetitive transcranial magnetic stimulation (rTMS) using continuous theta burst stimulation (cTBS) inhibitory paradigms over the primary motor cortex (M1) in patients with ALS.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Safety and Feasibility of cTBS rTMS in patients with ALS
  time frame: One Week before and after cTBS treatment
  description: Incidence of AEs and SAEs after accelerated continuous theta burst stimulation inhibitory intervention in individuals with ALS through the incidence of repetitive TMS treatment related adverse events, serious adverse events, discontinuations due to adverse events/serious adverse events, or accelerated ALS disease progression as defined by ≥6-point decline in the ALSFRS-R scores.
  measure: Corticospinal Excitability change measured by TMS Resting Motor Threshold
  time frame: One and Three Weeks after cTBS treatment
  description: Change from baseline in Resting Motor Threshold (RMT)
  measure: Corticospinal Excitability change measured by TMS Short Intracortical Inhibition
  time frame: One and Three Weeks after cTBS treatment
  description: Change from baseline in Short Intracortical Inhibition (SICI)
  measure: Corticospinal Excitability change measured by TMS Short Intracortical Facilitation
  time frame: One and Three Weeks after cTBS treatment
  description: Change from baseline in Short Intracortical Facilitation (SICF)
  measure: Corticospinal Excitability change measured by TMS Cortical Silent Period
  time frame: One and Three Weeks after cTBS treatment
  description: Change from baseline in Cortical Silent Period (CSP)
  measure: Magnetic Resonance Spectroscopy parameters as measured by 1H-MRS
  time frame: One Week after cTBS treatment
  description: Change from baseline in Glutamate/GABA ratio
  measure: Neurofilament-light chain levels
  time frame: Three Weeks after cTBS treatment
  description: Change from baseline in concentration of serum neurofilament light chain
  arm group label: Accelerated cTBS Neuromodulation
  arm group type: Experimental
  description: ALS patients receiving an accelerated schedule of continuous theta burst rTMS at a regimen of 40 seconds per treatment, for 5-6 treatment sessions per day, delivered one per hour, over 5 days (up to possible total 30 treatments).
  intervention type: Device
  intervention name: Repetitive Transcranial Magnetic Stimulation
  description: Accelerated rTMS using continuous theta burst stimulation inhibitory paradigms over unilateral M1 hand region outputted at 90% of resting motor threshold, using bursts of 3 pulses at 50 Hz. Bursts are repeated at 5 Hz for a total of 600 pulses over 40 seconds. ALS patients will receive rTMS at a regimen of cTBS for 40 seconds per treatment, for 5-6 treatment sessions per day, delivered one per hour, over 5 days (up to possible total 30 treatments).
  arm group label: Accelerated cTBS Neuromodulation
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Agessandro Abrahao, Dr.
  role: Principal Investigator
  affiliation: Sunnybrook Health Sciences Centre; University of Toronto
  last name: Lorne Zinman, Dr.
  role: Principal Investigator
  affiliation: Sunnybrook Health Sciences Centre; University of Toronto
  last name: Sean Nestor, Dr.
  role: Principal Investigator
  affiliation: Sunnybrook Research Institute; University of Toronto
  last name: Agessandro Abrahao, Dr.
  phone: (416) 480-6100
  phone ext: 87561
  email: alsresearch@sunnybrook.ca
  last name: Jahan Mookshah
  phone: 416 480-6100
  phone ext: 87561
  email: jahan.mookshah@sunnybrook.ca
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  investigator: 
  country: Canada
  responsible party type: Sponsor
  mesh term: Motor Neuron Disease
  mesh term: Amyotrophic Lateral Sclerosis
  mesh term: Sclerosis
  sharing ipd: No