<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/NCT03836950</url>
  </required_header>
  <id_info>
    <org_study_id>N2938-W</org_study_id>
    <secondary_id>IK2RX002938</secondary_id>
    <nct_id>NCT03836950</nct_id>
  </id_info>
  <brief_title>rTMS to Improve Cognition in Parkinson's</brief_title>
  <acronym>TMSCogReP</acronym>
  <official_title>rTMS as a Cognitive Rehabilitation Approach in Veterans With Parkinson'sDisease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to examine safety, feasibility, and the behavioral and brain&#xD;
      effects of a non-invasive treatment, repetitive transcranial magnetic stimulation (rTMS), for&#xD;
      Veterans with Parkinson's disease and mild impairments in their thinking. The hypothesis is&#xD;
      that rTMS can improve thinking for people with Parkinson's disease who are experiencing mild&#xD;
      problems with their thinking ability.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Repetitive transcranial magnetic stimulation (rTMS) shows promise as an effective cognitive&#xD;
      neurorehabilitation treatment. To date, no rTMS studies have assessed the effect of rTMS on&#xD;
      cognitive function in PD-MCI. Nor has there been PD neurophysiological studies using rTMS to&#xD;
      examine neural plasticity in cognitive neural networks. This study seeks to fill this gap by&#xD;
      conducting a small scaled pilot randomized controlled trial (RCT) designed to assess the&#xD;
      safety and therapeutic effects of rTMS on cognitive outcomes as well as on brain connectivity&#xD;
      in Veterans with PD-MCI. PD-MCI participants will be randomized to either active rTMS or sham&#xD;
      rTMS. Participants will complete a standardized neurocognitive battery assessment at&#xD;
      baseline, endpoint and at a one month follow-up. The primary outcome is change in executive&#xD;
      function. Secondary outcomes include performance on other cognitive domain tasks and a&#xD;
      proximal measure of real-life function that captures relevant functional changes related to&#xD;
      cognitive impairment in PD. Multi-modal neuroimaging, in a subsample of participants, will be&#xD;
      used to study neural connectivity changes induced by rTMS. Changes in resting state&#xD;
      functional connectivity, grey matter volume via voxel-based morphometry and white matter&#xD;
      integrity via diffusion tensor imaging will be assessed at baseline and endpoint. To inform&#xD;
      how to optimize rTMS treatment in PD-MCI, these changes will be correlated with changes in&#xD;
      cognitive performance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2020</start_date>
  <completion_date type="Anticipated">June 16, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 26, 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>randomized control trial. Participants will receive either active or sham rTMS</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change in NIH sponsored Executive Abilities: Measures and Instruments for neurobehavioral evaluation and re-search (NIH-EXAMINER) executive composite score</measure>
    <time_frame>baseline, 8 weeks, 12 weeks</time_frame>
    <description>The NIH-EXAMINER has an established 3-factor model defined by (1) cognitive control, (2) working memory (3) fluency. A confirmatory factor analysis indicates these 3-factors load on to 1-factor: executive composite score. Seven tests in the NIH-EXAMINER will be used to compute the composite score</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">56</enrollment>
  <condition>Parkinson's Disease</condition>
  <condition>Mild Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>active rTMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For active rTMS, a butterfly coil and MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark) will be used. One rTMS session will consist of 40 trains of 5sec each at 110% of resting motor threshold and 15Hz will be provided at the left DLPFC.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sham rTMS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>For sham rTMS, the procedure will be carried out at the left DLPFC but a sham coil will be used. The MagVenture coil has an active side and a placebo side allowing a double-blind study to be conducted. The sham system looks, sounds and feels like active rTMS.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark)</intervention_name>
    <description>The coil will be held tangentially to the skull at approximately 45� from the midline. One rTMS session will consist of 40 trains of 5sec each at 110% of resting motor threshold and 15Hz will be provided at the left DLPFC.</description>
    <arm_group_label>active rTMS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark)</intervention_name>
    <description>The coil will be held tangentially to the skull at approximately 45� from the midline. The sham coil will not release any stimulation, but it will look, feel and sound like the real rTMS</description>
    <arm_group_label>sham rTMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Veterans who seek services at Hines VA Hospital or Jesse Brown VA Medical Center&#xD;
&#xD;
          -  Diagnosis of PD as determined by the UK Parkinson's Disease Society Brain Bank&#xD;
             Diagnostic Criteria&#xD;
&#xD;
          -  Meet criteria for having mild cognitive impairment&#xD;
&#xD;
          -  Receiving stable (i.e., no changes in medication and medication dose) medication and&#xD;
             who are expected to remain on stable medication for the duration of the RCT&#xD;
&#xD;
          -  Speak and read English&#xD;
&#xD;
          -  50 years or older&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Dementia&#xD;
&#xD;
          -  Failure to demonstrate decision making capacity&#xD;
&#xD;
          -  History of deep brain stimulation surgery&#xD;
&#xD;
          -  Severe depression&#xD;
&#xD;
          -  Resting head tremor&#xD;
&#xD;
          -  Dyskinesia that will interfere with collecting imaging data&#xD;
&#xD;
          -  Has congestive heart failure&#xD;
&#xD;
          -  Implanted cardiac pacemaker or defibrillator&#xD;
&#xD;
          -  Cochlear implant, nerve stimulator, or intracranial metal clips&#xD;
&#xD;
          -  Implanted medical pump&#xD;
&#xD;
          -  Increased intracranial pressure&#xD;
&#xD;
          -  History of claustrophobia&#xD;
&#xD;
          -  Metal in eyes/face, shrapnel/bullet remnants in brain&#xD;
&#xD;
          -  Participants at potential increased risk of seizure including those who have the&#xD;
             following:&#xD;
&#xD;
               -  history (or family history) of seizure or epilepsy&#xD;
&#xD;
               -  history of stroke, head injury, or unexplained seizures&#xD;
&#xD;
               -  presence of other neurological disease that may be associated with an altered&#xD;
                  seizure threshold&#xD;
&#xD;
                    -  such as CVA, cerebral aneurysm, dementia, increased intracranial pressure&#xD;
&#xD;
          -  Concurrent medication use such as tricyclic antidepressants, neuroleptic medications,&#xD;
             any other drug known to lower seizure threshold&#xD;
&#xD;
          -  Secondary conditions that may significantly alter electrolyte balance or lower seizure&#xD;
             threshold&#xD;
&#xD;
          -  No quantifiable motor threshold such that rTMS dosage cannot be accurately deter-mined&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sandra L. Kletzel, PhD BA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Edward Hines Jr. VA Hospital, Hines, IL</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sandra L Kletzel, PhD BA</last_name>
    <phone>(708) 202-5735</phone>
    <email>Sandra.Kletzel@va.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Elyse Walsh, MS</last_name>
    <phone>(708) 968-0427</phone>
    <email>elyse.walsh@va.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Jesse Brown VA Medical Center, Chicago, IL</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sandra L Kletzel, PhD</last_name>
      <phone>708-202-5735</phone>
      <email>sandra.kletzel@va.gov</email>
    </contact>
    <contact_backup>
      <last_name>Elyse Walsh, MS</last_name>
      <phone>7089680427</phone>
      <email>elyse.walsh@va.gov</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Edward Hines Jr. VA Hospital, Hines, IL</name>
      <address>
        <city>Hines</city>
        <state>Illinois</state>
        <zip>60141-5000</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>William Wolf, PhD</last_name>
      <phone>708-202-5689</phone>
      <email>William.Wolf@va.gov</email>
    </contact>
    <contact_backup>
      <last_name>Susan Andrese, MHA</last_name>
      <phone>(708) 202-8387</phone>
      <phone_ext>27447</phone_ext>
      <email>Susan.Andrese@va.gov</email>
    </contact_backup>
    <investigator>
      <last_name>Sandra L. Kletzel, PhD BA</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>October 19, 2022</last_update_submitted>
  <last_update_submitted_qc>October 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>rTMS</keyword>
  <keyword>Parkinson's disease</keyword>
  <keyword>mild cognitive impairment</keyword>
  <keyword>executive function</keyword>
  <keyword>neuromodulation</keyword>
  <keyword>functional connectivity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Raw and/or normalized data will be made available in the form of Excel files. MRI images will anonymized and made available through the Northwestern University Neuroimaging Data Archive (NUNDA).</ipd_description>
    <ipd_time_frame>Final data sets will be made available as per Hines VA Hospital local policy for long term storage and access until enterprise-level resources become available.</ipd_time_frame>
    <ipd_access_criteria>These data will be available upon request by researchers and scientists in accordance with federal guidelines and Hines local policy.</ipd_access_criteria>
  </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/NCT03836950
org study id: N2938-W
secondary id: IK2RX002938
nct id: NCT03836950
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The purpose of this study is to examine safety, feasibility, and the behavioral and brain
      effects of a non-invasive treatment, repetitive transcranial magnetic stimulation (rTMS), for
      Veterans with Parkinson's disease and mild impairments in their thinking. The hypothesis is
      that rTMS can improve thinking for people with Parkinson's disease who are experiencing mild
      problems with their thinking ability.
Repetitive transcranial magnetic stimulation (rTMS) shows promise as an effective cognitive
      neurorehabilitation treatment. To date, no rTMS studies have assessed the effect of rTMS on
      cognitive function in PD-MCI. Nor has there been PD neurophysiological studies using rTMS to
      examine neural plasticity in cognitive neural networks. This study seeks to fill this gap by
      conducting a small scaled pilot randomized controlled trial (RCT) designed to assess the
      safety and therapeutic effects of rTMS on cognitive outcomes as well as on brain connectivity
      in Veterans with PD-MCI. PD-MCI participants will be randomized to either active rTMS or sham
      rTMS. Participants will complete a standardized neurocognitive battery assessment at
      baseline, endpoint and at a one month follow-up. The primary outcome is change in executive
      function. Secondary outcomes include performance on other cognitive domain tasks and a
      proximal measure of real-life function that captures relevant functional changes related to
      cognitive impairment in PD. Multi-modal neuroimaging, in a subsample of participants, will be
      used to study neural connectivity changes induced by rTMS. Changes in resting state
      functional connectivity, grey matter volume via voxel-based morphometry and white matter
      integrity via diffusion tensor imaging will be assessed at baseline and endpoint. To inform
      how to optimize rTMS treatment in PD-MCI, these changes will be correlated with changes in
      cognitive performance.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: randomized control trial. Participants will receive either active or sham rTMS
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: change in NIH sponsored Executive Abilities: Measures and Instruments for neurobehavioral evaluation and re-search (NIH-EXAMINER) executive composite score
time frame: baseline, 8 weeks, 12 weeks
description: The NIH-EXAMINER has an established 3-factor model defined by (1) cognitive control, (2) working memory (3) fluency. A confirmatory factor analysis indicates these 3-factors load on to 1-factor: executive composite score. Seven tests in the NIH-EXAMINER will be used to compute the composite score
arm group label: active rTMS
arm group type: Experimental
description: For active rTMS, a butterfly coil and MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark) will be used. One rTMS session will consist of 40 trains of 5sec each at 110% of resting motor threshold and 15Hz will be provided at the left DLPFC.
arm group label: sham rTMS
arm group type: Sham Comparator
description: For sham rTMS, the procedure will be carried out at the left DLPFC but a sham coil will be used. The MagVenture coil has an active side and a placebo side allowing a double-blind study to be conducted. The sham system looks, sounds and feels like active rTMS.
intervention type: Device
intervention name: MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark)
description: The coil will be held tangentially to the skull at approximately 45� from the midline. One rTMS session will consist of 40 trains of 5sec each at 110% of resting motor threshold and 15Hz will be provided at the left DLPFC.
arm group label: active rTMS
intervention type: Device
intervention name: MagVenture MagProX100 stimulator (MagVenture, Falun, Denmark)
description: The coil will be held tangentially to the skull at approximately 45� from the midline. The sham coil will not release any stimulation, but it will look, feel and sound like the real rTMS
arm group label: sham rTMS
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Sandra L. Kletzel, PhD BA
role: Principal Investigator
affiliation: Edward Hines Jr. VA Hospital, Hines, IL
last name: Sandra L Kletzel, PhD BA
phone: (708) 202-5735
email: Sandra.Kletzel@va.gov
last name: Elyse Walsh, MS
phone: (708) 968-0427
email: elyse.walsh@va.gov
facility: 
status: Not yet recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Cognitive Dysfunction
sharing ipd: Yes
ipd description: Raw and/or normalized data will be made available in the form of Excel files. MRI images will anonymized and made available through the Northwestern University Neuroimaging Data Archive (NUNDA).
ipd time frame: Final data sets will be made available as per Hines VA Hospital local policy for long term storage and access until enterprise-level resources become available.
ipd access criteria: These data will be available upon request by researchers and scientists in accordance with federal guidelines and Hines local policy.