<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/NCT03271736</url>
  </required_header>
  <id_info>
    <org_study_id>201609085RINA</org_study_id>
    <nct_id>NCT03271736</nct_id>
  </id_info>
  <brief_title>Effects of Rhythmic Auditory Cueing on Stepping in Place in Patients With Parkinson's Disease</brief_title>
  <official_title>Effects of Rhythmic Auditory Cueing on Stepping in Place in Patients With Parkinson's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>HsiuYun Chang</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University</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>
      Patients with Parkinson's disease have internal rhythm dysfunction, which may affect the&#xD;
      rhythmic movements such as walking. Poor regularity of the rhythmic movement may lead to&#xD;
      freezing of gait. This study will apply rhythmic auditory cues on the stepping-in-place&#xD;
      training and the investigators will examine if the behavior and neuroelectrophysiology would&#xD;
      change after auditory cueing training. The investigators hypothesize the variation of&#xD;
      rhythmic movements such as walking and stepping-in-place will be reduced, and the cortical&#xD;
      excitability would be modulated after training.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Parkinson's disease is a common neurodegenerative disease and movement disorder. Due to the&#xD;
      degeneration of basal ganglia, patients with Parkinson's disease also demonstrate internal&#xD;
      rhythm dysfunction, thus will lead to difficulty in rhythmic movements such as ambulation.&#xD;
      For improving the rhythmic movement problem, auditory cues are often used in clinical setting&#xD;
      and shows benefits in ambulation and freezing problems. Previous studies often use finger&#xD;
      tapping test and ambulation to assess the rhythmic movement problem. No study uses stepping&#xD;
      in place movements as a test to examine rhythmic problem. Little study investigates the&#xD;
      effects of auditory cues on brain cortical excitability. In this cross-over study,&#xD;
      participants will receive 2 times of training include stepping-in-place exercise with and&#xD;
      without auditory cues in random orders. Auditory cues are given via the metronome. There is&#xD;
      one-week wash-out period between two trainings. Movement tests such as walking and&#xD;
      stepping-in-place and transcranial magnetic stimulation (TMS) are carried out before and&#xD;
      after each training.&#xD;
&#xD;
      The investigators hypothesize the variation of rhythmic movements such as walking and&#xD;
      stepping-in-place will be reduced more, and the cortical excitability would be modulated&#xD;
      after the training with auditory cues, comparing with the other training without auditory&#xD;
      cues.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 8, 2018</start_date>
  <completion_date type="Actual">June 30, 2018</completion_date>
  <primary_completion_date type="Actual">May 30, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes of transcranial magnetic stimulation (TMS) parameters</measure>
    <time_frame>TMS parameters are assessed immediately before and after a 30-minute intervention. The data will be reported through study completion, for average of 6 months.</time_frame>
    <description>Single-pulse and paired-pulse TMS are used to measure the cortical excitability of the motor cortex and the integrity of the intracortical inhibitory/facilitatory circuits. The TMS parameters include motor threshold (MT), motor evoke potential, silent period, short intracortical inhibition and facilitation. In single-pulse condition, the stimulation intensity is set at 130% of the MT. While in the paired-pulse condition, the first conditioning stimulus is set at 80% of MT, the second test stimulus is set at 130% of MT.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Variation of walking step time</measure>
    <time_frame>The step time variability is assessed immediately before and after a 30-minute intervention. The data will be reported through study completion, for average of 6 months.</time_frame>
    <description>Subjects are asked to walk on a GAITRite carpet under usual walking speed. Duration between each step can be recorded through the system.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Walking ability</measure>
    <time_frame>The walking ability is assessed immediately before and after a 30-minute intervention. The data will be reported through study completion, for average of 6 months.</time_frame>
    <description>Walking speed, stride length and cadence are recorded as secondary outcome measures. Subjects are asked to walk on a GAITRite carpet under usual walking speed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation of stepping-in-place movement</measure>
    <time_frame>The step variability is assessed immediately before and after a 30-minute intervention. The data will be reported through study completion, for average of 6 months.</time_frame>
    <description>Subjects are asked to stand and do stepping-in-place movement on a force plate.We use force plate to detect the vertical force and calculate the variation of each step.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Freezer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All the subjects received 2 experiments. 2 experiments contain 20 mins stepping-in-place exercise and pre-/post assessments. The difference between 2 experiments is the application of auditory cues. One of the 2 experiment includes stepping-in-place exercise with auditory cues from the metronome (Stepping-in-place exercise with external auditory cues), in the other experiment we ask the subjects to follow their internal rhythm without external auditory cues (Stepping-in-place exercise without external auditory cues). Transcranial magnetic stimulation (TMS) is applied before and after the stepping-in-place exercise.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-freezer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All the subjects received 2 experiments. 2 experiments contain 20 mins stepping-in-place exercise and pre-/post assessments. The difference between 2 experiments is the application of auditory cues. One of the 2 experiment includes stepping-in-place exercise with auditory cues from the metronome (Stepping-in-place exercise with external auditory cues), in the other experiment we ask the subjects to follow their internal rhythm without external auditory cues (Stepping-in-place exercise without external auditory cues). Transcranial magnetic stimulation (TMS) is applied before and after the stepping-in-place exercise.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Stepping-in-place exercise with external auditory cues</intervention_name>
    <description>The stepping-in-place exercise includes 10-session training. In each session, subjects are asked for stepping for 50 steps. In auditory cued condition, the cued frequency is set at 110% of the usual walking cadence. While in non-cued condition, we ask the subjects to step according to their own internal rhythm.</description>
    <arm_group_label>Freezer</arm_group_label>
    <arm_group_label>Non-freezer</arm_group_label>
    <other_name>Stepping-in-place exercise without external auditory cues</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial magnetic stimulation (TMS)</intervention_name>
    <description>TMS is used to assess the cortical excitability of the motor cortex. The stimulation intensity is set at 130% of the motor threshold in single-pulse condition. In paired-pulse condition, the first stimulus is set at 80% of the motor threshold and the second stimulus is set at 130% of the motor threshold.</description>
    <arm_group_label>Freezer</arm_group_label>
    <arm_group_label>Non-freezer</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        [Patients with Parkinson's disease]&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with idiopathic Parkinson's disease&#xD;
&#xD;
          -  No hearing impairment&#xD;
&#xD;
          -  Able to walk independently for at least 10m&#xD;
&#xD;
          -  Able to follow command (MMSE &gt;=24)&#xD;
&#xD;
        [Healthy subjects]&#xD;
&#xD;
          -  No hearing impairment&#xD;
&#xD;
          -  Able to walk independently for at least 10m&#xD;
&#xD;
          -  Able to follow command (MMSE &gt;=24)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  With other neurological diseases or psychological diseases&#xD;
&#xD;
          -  Dementia&#xD;
&#xD;
          -  Family history of epilepsy&#xD;
&#xD;
          -  History of head trauma, surgery, or metal implants&#xD;
&#xD;
          -  Having pacemaker or other electrical stimulators&#xD;
&#xD;
          -  History of syncopes or frequent migraines&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jau Yih Tsauo, PT, phD</last_name>
    <role>Study Chair</role>
    <affiliation>department of physical therapy, college of medicine, National Taiwan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of physical therapy, National Taiwan University</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 6, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>March 29, 2019</last_update_submitted>
  <last_update_submitted_qc>March 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>National Taiwan University</investigator_affiliation>
    <investigator_full_name>HsiuYun Chang</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Parkinson's disease</keyword>
  <keyword>Auditory cues</keyword>
  <keyword>step in place</keyword>
  <keyword>transcranial magnetic stimulation</keyword>
  <keyword>cortical excitability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</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/NCT03271736
org study id: 201609085RINA
nct id: NCT03271736
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with Parkinson's disease have internal rhythm dysfunction, which may affect the
      rhythmic movements such as walking. Poor regularity of the rhythmic movement may lead to
      freezing of gait. This study will apply rhythmic auditory cues on the stepping-in-place
      training and the investigators will examine if the behavior and neuroelectrophysiology would
      change after auditory cueing training. The investigators hypothesize the variation of
      rhythmic movements such as walking and stepping-in-place will be reduced, and the cortical
      excitability would be modulated after training.
Parkinson's disease is a common neurodegenerative disease and movement disorder. Due to the
      degeneration of basal ganglia, patients with Parkinson's disease also demonstrate internal
      rhythm dysfunction, thus will lead to difficulty in rhythmic movements such as ambulation.
      For improving the rhythmic movement problem, auditory cues are often used in clinical setting
      and shows benefits in ambulation and freezing problems. Previous studies often use finger
      tapping test and ambulation to assess the rhythmic movement problem. No study uses stepping
      in place movements as a test to examine rhythmic problem. Little study investigates the
      effects of auditory cues on brain cortical excitability. In this cross-over study,
      participants will receive 2 times of training include stepping-in-place exercise with and
      without auditory cues in random orders. Auditory cues are given via the metronome. There is
      one-week wash-out period between two trainings. Movement tests such as walking and
      stepping-in-place and transcranial magnetic stimulation (TMS) are carried out before and
      after each training.

      The investigators hypothesize the variation of rhythmic movements such as walking and
      stepping-in-place will be reduced more, and the cortical excitability would be modulated
      after the training with auditory cues, comparing with the other training without auditory
      cues.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes of transcranial magnetic stimulation (TMS) parameters
time frame: TMS parameters are assessed immediately before and after a 30-minute intervention. The data will be reported through study completion, for average of 6 months.
description: Single-pulse and paired-pulse TMS are used to measure the cortical excitability of the motor cortex and the integrity of the intracortical inhibitory/facilitatory circuits. The TMS parameters include motor threshold (MT), motor evoke potential, silent period, short intracortical inhibition and facilitation. In single-pulse condition, the stimulation intensity is set at 130% of the MT. While in the paired-pulse condition, the first conditioning stimulus is set at 80% of MT, the second test stimulus is set at 130% of MT.
measure: Variation of walking step time
time frame: The step time variability is assessed immediately before and after a 30-minute intervention. The data will be reported through study completion, for average of 6 months.
description: Subjects are asked to walk on a GAITRite carpet under usual walking speed. Duration between each step can be recorded through the system.
measure: Walking ability
time frame: The walking ability is assessed immediately before and after a 30-minute intervention. The data will be reported through study completion, for average of 6 months.
description: Walking speed, stride length and cadence are recorded as secondary outcome measures. Subjects are asked to walk on a GAITRite carpet under usual walking speed.
measure: Variation of stepping-in-place movement
time frame: The step variability is assessed immediately before and after a 30-minute intervention. The data will be reported through study completion, for average of 6 months.
description: Subjects are asked to stand and do stepping-in-place movement on a force plate.We use force plate to detect the vertical force and calculate the variation of each step.
arm group label: Freezer
arm group type: Experimental
description: All the subjects received 2 experiments. 2 experiments contain 20 mins stepping-in-place exercise and pre-/post assessments. The difference between 2 experiments is the application of auditory cues. One of the 2 experiment includes stepping-in-place exercise with auditory cues from the metronome (Stepping-in-place exercise with external auditory cues), in the other experiment we ask the subjects to follow their internal rhythm without external auditory cues (Stepping-in-place exercise without external auditory cues). Transcranial magnetic stimulation (TMS) is applied before and after the stepping-in-place exercise.
arm group label: Non-freezer
arm group type: Experimental
description: All the subjects received 2 experiments. 2 experiments contain 20 mins stepping-in-place exercise and pre-/post assessments. The difference between 2 experiments is the application of auditory cues. One of the 2 experiment includes stepping-in-place exercise with auditory cues from the metronome (Stepping-in-place exercise with external auditory cues), in the other experiment we ask the subjects to follow their internal rhythm without external auditory cues (Stepping-in-place exercise without external auditory cues). Transcranial magnetic stimulation (TMS) is applied before and after the stepping-in-place exercise.
intervention type: Behavioral
intervention name: Stepping-in-place exercise with external auditory cues
description: The stepping-in-place exercise includes 10-session training. In each session, subjects are asked for stepping for 50 steps. In auditory cued condition, the cued frequency is set at 110% of the usual walking cadence. While in non-cued condition, we ask the subjects to step according to their own internal rhythm.
arm group label: Freezer
arm group label: Non-freezer
other name: Stepping-in-place exercise without external auditory cues
intervention type: Device
intervention name: Transcranial magnetic stimulation (TMS)
description: TMS is used to assess the cortical excitability of the motor cortex. The stimulation intensity is set at 130% of the motor threshold in single-pulse condition. In paired-pulse condition, the first stimulus is set at 80% of the motor threshold and the second stimulus is set at 130% of the motor threshold.
arm group label: Freezer
arm group label: Non-freezer
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jau Yih Tsauo, PT, phD
role: Study Chair
affiliation: department of physical therapy, college of medicine, National Taiwan University
facility: 
country: Taiwan
responsible party type: Sponsor-Investigator
investigator affiliation: National Taiwan University
investigator full name: HsiuYun Chang
investigator title: Principal Investigator
mesh term: Parkinson Disease
sharing ipd: No