<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/NCT04468932</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY0020341</org_study_id>
    <secondary_id>KL2TR002370</secondary_id>
    <secondary_id>P2CHD086844</secondary_id>
    <nct_id>NCT04468932</nct_id>
  </id_info>
  <brief_title>Transcranial Magnetic Stimulation in Progressive Supranuclear Palsy</brief_title>
  <official_title>Cerebellar Transcranial Magnetic Stimulation for Motor Control in Progressive Supranuclear Palsy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Center of Neuromodulation for Rehabilitation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Collins Medical Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Department of Health and Human Services</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Oregon Health and Science University</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>
      The objective of this proposal is to investigate the effect of non-invasive repetitive&#xD;
      cerebellar transcranial magnetic stimulation (rTMS) on motor control in progressive&#xD;
      supranuclear (PSP). The central hypothesis is that augmenting cerebellar inhibition via&#xD;
      cerebellar rTMS will decrease postural instability in patients with PSP. We will use&#xD;
      functional near infrared spectroscopy (fNIRS) to examine changes in motor and premotor&#xD;
      cortical activity after cerebellar rTMS.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 17, 2020</start_date>
  <completion_date type="Anticipated">April 2027</completion_date>
  <primary_completion_date type="Anticipated">January 2027</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>Crossover Assignment</intervention_model>
    <intervention_model_description>The investigators will use a single-blind crossover design with a 4 week TMS washout period. The subjects will serve as their own controls, thus limiting confounding variables such as medication or cognitive effect.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>The subjects will be blinded to the order of intervention, but the PI will not be blinded in order to perform the TMS intervention. The outcome evaluators will be blinded to the intervention, however.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>objective posturography</measure>
    <time_frame>assessed on 4 days during the 8 week study period</time_frame>
    <description>The primary endpoint is center of pressure shifts with tilt and with translation, and body sway in quiet stance.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>fNIRS</measure>
    <time_frame>assessed on 4 days during the 8 week study period</time_frame>
    <description>functional near infrared spectroscopy of premotor and motor areas during balance testing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>speech analysis</measure>
    <time_frame>assessed on 4 days during the 8 week study period</time_frame>
    <description>speech sample assessment conducted by investigator</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Palsy Supranuclear</condition>
  <condition>Supranuclear Palsy, Progressive</condition>
  <arm_group>
    <arm_group_label>Active TMS first</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After completing their baseline assessment, participants randomized to this arm will initially take part in a 2-week TMS intervention. After the midpoint assessment and subsequent a 1-month washout, these participants will then complete a 2-week sham TMS period prior to their final assessment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham treatment first</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After completing their baseline assessment, participants randomized to this arm will initially take part in a 2-week sham TMS period. After the midpoint assessment and subsequent a 1-month washout, these participants will then complete a 2-week TMS intervention prior to their final assessment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Repetitive transcranial magnetic stimulation (rTMS)</intervention_name>
    <description>Aim 1: To determine the clinical effects of rTMS targeting the cerebellum on postural instability in PSP. The hypothesis to be tested is that TMS augmentation of cerebellar inhibition will improve cerebellum-dependent balance symptoms of PSP for a period of time sufficient to improve rehabilitation outcomes. The investigators will measure a battery of objective posturography metrics and other measures of motor control, including sway and center of pressure changes to backward tilt and forward translation.&#xD;
Aim 2: We will use functional near infrared spectroscopy (fNIRS) to examine changes in motor and premotor cortical activity after cerebellar rTMS. The hypothesis to be tested is that premotor and motor cortical activity will decrease after cerebellar rTMS compared to sham TMS, reflecting improved cerebellar inhibition of the motor cortex after the intervention.</description>
    <arm_group_label>Active TMS first</arm_group_label>
    <arm_group_label>Sham treatment first</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  probable or possible PSP by the revised MDS PSP Criteria (Hoglinger 2017)&#xD;
&#xD;
          -  age 40-85 at time of screening&#xD;
&#xD;
          -  ability to understand and cooperate with simple instructions in English&#xD;
&#xD;
          -  ability to read at 6th grade reading level in English&#xD;
&#xD;
          -  ability to stand unassisted for at least 30 seconds and to be able walk independently&#xD;
             with a walker&#xD;
&#xD;
          -  ability to refrain from new physical and speech therapy programs for the duration of&#xD;
             the study&#xD;
&#xD;
          -  ability to remain on stable doses of any cholinergic, dopaminergic, serotonergic&#xD;
             sedative or NMDA receptor antagonists for the duration of the study&#xD;
&#xD;
          -  females of child-bearing age must perform a urine pregnancy test and be on reliable&#xD;
             birth control during the course of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  other significant neurological or vestibular disorders&#xD;
&#xD;
          -  presence of electrically, magnetically or mechanically activated implants or history&#xD;
             of injurious metal exposure in eyes, head, or body&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marian L Dale, MD, MCR</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oregon Health and Science University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Graham Harker</last_name>
    <phone>5034182601</phone>
    <email>balance@ohsu.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Graham Harker</last_name>
      <phone>503-418-2601</phone>
      <email>balance@ohsu.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>April 24, 2023</last_update_submitted>
  <last_update_submitted_qc>April 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oregon Health and Science University</investigator_affiliation>
    <investigator_full_name>Marian L Dale, MD</investigator_full_name>
    <investigator_title>Assistant Professor of Neurology, School of Medicine; Director, OHSU CurePSP Center of Care</investigator_title>
  </responsible_party>
  <keyword>repetitive transcranial magnetic stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paralysis</mesh_term>
    <mesh_term>Supranuclear Palsy, Progressive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04468932
org study id: STUDY0020341
secondary id: KL2TR002370
secondary id: P2CHD086844
nct id: NCT04468932
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
The objective of this proposal is to investigate the effect of non-invasive repetitive
      cerebellar transcranial magnetic stimulation (rTMS) on motor control in progressive
      supranuclear (PSP). The central hypothesis is that augmenting cerebellar inhibition via
      cerebellar rTMS will decrease postural instability in patients with PSP. We will use
      functional near infrared spectroscopy (fNIRS) to examine changes in motor and premotor
      cortical activity after cerebellar rTMS.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: The investigators will use a single-blind crossover design with a 4 week TMS washout period. The subjects will serve as their own controls, thus limiting confounding variables such as medication or cognitive effect.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: The subjects will be blinded to the order of intervention, but the PI will not be blinded in order to perform the TMS intervention. The outcome evaluators will be blinded to the intervention, however.
measure: objective posturography
time frame: assessed on 4 days during the 8 week study period
description: The primary endpoint is center of pressure shifts with tilt and with translation, and body sway in quiet stance.
measure: fNIRS
time frame: assessed on 4 days during the 8 week study period
description: functional near infrared spectroscopy of premotor and motor areas during balance testing
measure: speech analysis
time frame: assessed on 4 days during the 8 week study period
description: speech sample assessment conducted by investigator
arm group label: Active TMS first
arm group type: Experimental
description: After completing their baseline assessment, participants randomized to this arm will initially take part in a 2-week TMS intervention. After the midpoint assessment and subsequent a 1-month washout, these participants will then complete a 2-week sham TMS period prior to their final assessment.
arm group label: Sham treatment first
arm group type: Experimental
description: After completing their baseline assessment, participants randomized to this arm will initially take part in a 2-week sham TMS period. After the midpoint assessment and subsequent a 1-month washout, these participants will then complete a 2-week TMS intervention prior to their final assessment.
intervention type: Device
intervention name: Repetitive transcranial magnetic stimulation (rTMS)
description: Aim 1: To determine the clinical effects of rTMS targeting the cerebellum on postural instability in PSP. The hypothesis to be tested is that TMS augmentation of cerebellar inhibition will improve cerebellum-dependent balance symptoms of PSP for a period of time sufficient to improve rehabilitation outcomes. The investigators will measure a battery of objective posturography metrics and other measures of motor control, including sway and center of pressure changes to backward tilt and forward translation.
Aim 2: We will use functional near infrared spectroscopy (fNIRS) to examine changes in motor and premotor cortical activity after cerebellar rTMS. The hypothesis to be tested is that premotor and motor cortical activity will decrease after cerebellar rTMS compared to sham TMS, reflecting improved cerebellar inhibition of the motor cortex after the intervention.
arm group label: Active TMS first
arm group label: Sham treatment first
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: No
last name: Marian L Dale, MD, MCR
role: Principal Investigator
affiliation: Oregon Health and Science University
last name: Graham Harker
phone: 5034182601
email: balance@ohsu.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Oregon Health and Science University
investigator full name: Marian L Dale, MD
investigator title: Assistant Professor of Neurology, School of Medicine; Director, OHSU CurePSP Center of Care
mesh term: Paralysis
mesh term: Supranuclear Palsy, Progressive
sharing ipd: No