<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/NCT03243214</url>
  </required_header>
  <id_info>
    <org_study_id>REB15-1689</org_study_id>
    <nct_id>NCT03243214</nct_id>
  </id_info>
  <brief_title>Effect of Transcranial Magnetic Stimulation on Cognition and Neural Changes in Parkinson's Disease</brief_title>
  <acronym>PD-MCI-TMS</acronym>
  <official_title>Effect of Excitatory Theta-Burst Transcranial Magnetic Stimulation on Cognition in Patients With Both Parkinson's Disease and Mild Cognitive Impairment and Analysis of Functional and Structural Brain Changes After Stimulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Montreal Neurological Institute and Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>McGill University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Calgary</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>
      Parkinson's disease (PD) affects more than 100,000 Canadians and results in symptoms&#xD;
      affecting both motor and cognitive (thinking and memory) functions. Parkinson's disease with&#xD;
      Mild Cognitive Impairment (MCI) frequently results in development of dementia for which few&#xD;
      treatment options exist. Transcranial Magnetic Stimulation (TMS) is used to alter activity in&#xD;
      the outer regions of the brain and has been shown in previous studies to increase cognitive&#xD;
      performance in patients with different disorders. This study will investigate the&#xD;
      effectiveness of TMS as a clinical treatment for the cognitive deficits associated with&#xD;
      Parkinson's disease. 64 male and female participants between the ages of 50 and 90 will&#xD;
      attend eight study visits over a period of 63 to 66 days. This study is a double-blind&#xD;
      randomized clinical trial meaning the participant will be assigned by chance to either the&#xD;
      TMS-treatment group or the Sham-treatment group. Additionally, a combination of memory and&#xD;
      thinking tests and Magnetic Resonance Imaging (MRI) will be used to see if there are&#xD;
      structural and functional changes within the brain. Genotyping and blood analysis before and&#xD;
      after treatment for different biomarkers will also be performed and these data will be&#xD;
      compared to the TMS data. Initially, this research will increase knowledge about the effects&#xD;
      of TMS on various brain regions. Ultimately, we will be able to determine if TMS can be used&#xD;
      as a complementary therapy for PD to improve cognitive performance and to reduce progression&#xD;
      into dementia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Visit 1:&#xD;
&#xD;
      Informed Consent Neuropsychological Battery&#xD;
&#xD;
      Visit 2: (1-2 days later) Blood Draw Neuropsychiatric Assessment Questionnaires Companion&#xD;
      Questionnaire to take home UPDRS&#xD;
&#xD;
      Visit 3: (up to a week after visit 2) MRI Scan while performing Executive Task&#xD;
&#xD;
      Visit 4: (1-3 days after visit 3) TMS- or Sham-Treatment (two sessions , 20 min each, 1 hour&#xD;
      apart)&#xD;
&#xD;
      Visit 5: (2-3 days after visit 4) Same as Visit 4&#xD;
&#xD;
      Visit 6: (2-3 days after visit 5) Same as Visit 4&#xD;
&#xD;
      Visit 7: (1 day after visit 6) Neuropsychological Battery UPDRS&#xD;
&#xD;
      Visit 8: (1 day after visit 7) MRI Scan while performing Executive Task Blood Draw&#xD;
&#xD;
      Visit 9: (1 month after visit 6) Neuropsychological Battery UPDRS&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 24, 2016</start_date>
  <completion_date type="Actual">February 14, 2020</completion_date>
  <primary_completion_date type="Actual">February 14, 2020</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>Sequential Assignment</intervention_model>
    <intervention_model_description>This is a randomized double blind trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>The participant and investigator do not know what treatment is applied (TMS stimulation or Sham-TMS stimulation with a different coil).&#xD;
The outcomes assessor will also be blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>TMS stimulation applied to the left DLPFC has a quantifiable effect on cognition</measure>
    <time_frame>Neuropsychological Assessments: Baseline, one day after and one month after TMS stimulation</time_frame>
    <description>Changes in one or more of the five assessed brain domains at baseline and one day after stimulation will be measured by comparing the scores for the different neuropsychological tests.&#xD;
The same neuropsychological assessment one month after TMS stimulation will show, if possible changes from one day after are longer lasting and can still be seen.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in structural grey and white matter in the brain at baseline compared to after TMS stimulation</measure>
    <time_frame>MRI: Baseline and two days after TMS stimulation</time_frame>
    <description>MRI analysis will measure any changes in cortical thickness (mm) or other structural changes in the brain after TMS or Sham-TMS stimulation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in executive functioning measured as BOLD fMRI sequence</measure>
    <time_frame>MRI: Baseline and two days after TMS stimulation</time_frame>
    <description>The executive task, Wisconsin Card Sorting Task, will be performed in the scanner to measure the level of activation in the basal ganglia and the prefrontal cortex via BOLD functional MRI sequence to see changes after TMS stimulation compared to baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in levels of biomarkers of interest (alpha-synuclein and BDNF) in serum after TMS stimulation compared to baseline.</measure>
    <time_frame>Blood draws: Baseline and two days after TMS stimulation</time_frame>
    <description>Measure the concentration of alpha-synuclein and BDNF in serum at baseline and after TMS stimulation with the Meso Scale Discovery method. These assays are highly developed ELISA assays using electrochemiluminescence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genotyping</measure>
    <time_frame>Blood draw for DNA analysis: Baseline</time_frame>
    <description>Analyze DNA for following genes: COMT, DAT1, MAPT, ApoE, GBA, CHCRA4, SNCA, BDNF These genes of interest will be correlated to changes in the neuropsychological assessments.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Parkinson's Disease</condition>
  <condition>Mild Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>PD-MCI, TMS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The patient is treated with TMS stimulation according to protocol with an active coil.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PD-MCI, Sham-TMS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>The patient is treated with Sham-TMS stimulation according to protocol with an inactive coil.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>TMS</intervention_name>
    <description>Real or Sham TMS will be given to the PD-MCI patient</description>
    <arm_group_label>PD-MCI, TMS</arm_group_label>
    <other_name>Magstim</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham-TMS</intervention_name>
    <description>Real or Sham TMS will be given to the PD-MCI patient</description>
    <arm_group_label>PD-MCI, Sham-TMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of idiopathic Parkinson's disease any stage&#xD;
&#xD;
          -  Mild Cognitive Behaviour confirmed through neuropsychological assessment&#xD;
&#xD;
          -  MRI Compatibility&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Alcohol-dependency&#xD;
&#xD;
          -  Severe psychiatric disorder, neurological disorder, epilepsy or stroke&#xD;
&#xD;
          -  General anaesthesia in the past six months&#xD;
&#xD;
          -  History of cerebrovascular disorders&#xD;
&#xD;
          -  Colour-blindness&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oury Monchi, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Calgary, Department of Clinical Neurosciences</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4N1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <last_update_submitted>October 15, 2020</last_update_submitted>
  <last_update_submitted_qc>October 15, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Calgary</investigator_affiliation>
    <investigator_full_name>Oury Monchi</investigator_full_name>
    <investigator_title>Professor and Tourmaline Chair in Parkinson's Disease</investigator_title>
  </responsible_party>
  <keyword>Transcranial Magnetic Stimulation</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>
  <!-- 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/NCT03243214
org study id: REB15-1689
nct id: NCT03243214
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Parkinson's disease (PD) affects more than 100,000 Canadians and results in symptoms
      affecting both motor and cognitive (thinking and memory) functions. Parkinson's disease with
      Mild Cognitive Impairment (MCI) frequently results in development of dementia for which few
      treatment options exist. Transcranial Magnetic Stimulation (TMS) is used to alter activity in
      the outer regions of the brain and has been shown in previous studies to increase cognitive
      performance in patients with different disorders. This study will investigate the
      effectiveness of TMS as a clinical treatment for the cognitive deficits associated with
      Parkinson's disease. 64 male and female participants between the ages of 50 and 90 will
      attend eight study visits over a period of 63 to 66 days. This study is a double-blind
      randomized clinical trial meaning the participant will be assigned by chance to either the
      TMS-treatment group or the Sham-treatment group. Additionally, a combination of memory and
      thinking tests and Magnetic Resonance Imaging (MRI) will be used to see if there are
      structural and functional changes within the brain. Genotyping and blood analysis before and
      after treatment for different biomarkers will also be performed and these data will be
      compared to the TMS data. Initially, this research will increase knowledge about the effects
      of TMS on various brain regions. Ultimately, we will be able to determine if TMS can be used
      as a complementary therapy for PD to improve cognitive performance and to reduce progression
      into dementia.
Visit 1:

      Informed Consent Neuropsychological Battery

      Visit 2: (1-2 days later) Blood Draw Neuropsychiatric Assessment Questionnaires Companion
      Questionnaire to take home UPDRS

      Visit 3: (up to a week after visit 2) MRI Scan while performing Executive Task

      Visit 4: (1-3 days after visit 3) TMS- or Sham-Treatment (two sessions , 20 min each, 1 hour
      apart)

      Visit 5: (2-3 days after visit 4) Same as Visit 4

      Visit 6: (2-3 days after visit 5) Same as Visit 4

      Visit 7: (1 day after visit 6) Neuropsychological Battery UPDRS

      Visit 8: (1 day after visit 7) MRI Scan while performing Executive Task Blood Draw

      Visit 9: (1 month after visit 6) Neuropsychological Battery UPDRS
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: This is a randomized double blind trial.
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: The participant and investigator do not know what treatment is applied (TMS stimulation or Sham-TMS stimulation with a different coil).
The outcomes assessor will also be blinded.
measure: TMS stimulation applied to the left DLPFC has a quantifiable effect on cognition
time frame: Neuropsychological Assessments: Baseline, one day after and one month after TMS stimulation
description: Changes in one or more of the five assessed brain domains at baseline and one day after stimulation will be measured by comparing the scores for the different neuropsychological tests.
The same neuropsychological assessment one month after TMS stimulation will show, if possible changes from one day after are longer lasting and can still be seen.
measure: Change in structural grey and white matter in the brain at baseline compared to after TMS stimulation
time frame: MRI: Baseline and two days after TMS stimulation
description: MRI analysis will measure any changes in cortical thickness (mm) or other structural changes in the brain after TMS or Sham-TMS stimulation
measure: Change in executive functioning measured as BOLD fMRI sequence
time frame: MRI: Baseline and two days after TMS stimulation
description: The executive task, Wisconsin Card Sorting Task, will be performed in the scanner to measure the level of activation in the basal ganglia and the prefrontal cortex via BOLD functional MRI sequence to see changes after TMS stimulation compared to baseline.
measure: Change in levels of biomarkers of interest (alpha-synuclein and BDNF) in serum after TMS stimulation compared to baseline.
time frame: Blood draws: Baseline and two days after TMS stimulation
description: Measure the concentration of alpha-synuclein and BDNF in serum at baseline and after TMS stimulation with the Meso Scale Discovery method. These assays are highly developed ELISA assays using electrochemiluminescence.
measure: Genotyping
time frame: Blood draw for DNA analysis: Baseline
description: Analyze DNA for following genes: COMT, DAT1, MAPT, ApoE, GBA, CHCRA4, SNCA, BDNF These genes of interest will be correlated to changes in the neuropsychological assessments.
arm group label: PD-MCI, TMS
arm group type: Active Comparator
description: The patient is treated with TMS stimulation according to protocol with an active coil.
arm group label: PD-MCI, Sham-TMS
arm group type: Sham Comparator
description: The patient is treated with Sham-TMS stimulation according to protocol with an inactive coil.
intervention type: Device
intervention name: TMS
description: Real or Sham TMS will be given to the PD-MCI patient
arm group label: PD-MCI, TMS
other name: Magstim
intervention type: Device
intervention name: Sham-TMS
description: Real or Sham TMS will be given to the PD-MCI patient
arm group label: PD-MCI, Sham-TMS
criteria: 
gender: All
minimum age: 50 Years
maximum age: 90 Years
healthy volunteers: No
last name: Oury Monchi, PhD
role: Principal Investigator
affiliation: University of Calgary
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Calgary
investigator full name: Oury Monchi
investigator title: Professor and Tourmaline Chair in Parkinson's Disease
mesh term: Parkinson Disease
mesh term: Cognitive Dysfunction