<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/NCT04448444</url>
  </required_header>
  <id_info>
    <org_study_id>EK-VP/22/0/2014/2</org_study_id>
    <nct_id>NCT04448444</nct_id>
  </id_info>
  <brief_title>Brain Activity Changes Following Neuroproprioceptive Physiotherapy in Multiple Sclerosis</brief_title>
  <official_title>Brain Activity Changes Following Neuroproprioceptive Physiotherapy in Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Charles University, Czech Republic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Charles University, Czech Republic</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Imaging methods bring new possibilities for describing the brain plasticity processes that&#xD;
      underly the improvement of clinical function after physiotherapy in people with multiple&#xD;
      sclerosis (pwMS). The study determined whether facilitation physiotherapy could enhance brain&#xD;
      plasticity, compared two facilitation methods, and looked for any relation to clinical&#xD;
      improvement in pwMS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study was designed as parallel group randomized comparison of two kinds of&#xD;
      physiotherapeutic interventions referred to healthy controls.&#xD;
&#xD;
      MS patients were examined by fMRI (primary outcomes) and clinical tests (secondary outcomes)&#xD;
      at the beginning of study. Then, they were randomly divided into two groups (by drawing lots&#xD;
      in a 1:1 ratio). The first group underwent Vojta reflex locomotion (VRL), and the second&#xD;
      Motor Program Activating Physiotherapy (MPAT). The length and intensity of treatment was the&#xD;
      same in both groups (two months, one hour twice a week). After the treatment, a clinical and&#xD;
      fMRI examination was performed. Healthy volunteers underwent an fMRI examination that was&#xD;
      considered to be a control.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2015</start_date>
  <completion_date type="Actual">November 10, 2019</completion_date>
  <primary_completion_date type="Actual">May 15, 2017</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>Parallel Assignment</intervention_model>
    <intervention_model_description>The study was designed as parallel group (outpatients) randomized comparison of two kinds of physiotherapeutic interventions referred to healthy controls.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Brain activity</measure>
    <time_frame>0 month</time_frame>
    <description>fMRI examinations on 3T magnetic resonance scanner (Siemens Trio Tim, Erlangen, Germany) using a 12-channel head coil (different pattern of brain activity in healthy and people with MS)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Brain activity</measure>
    <time_frame>0 and 2 months</time_frame>
    <description>fMRI examinations on 3T magnetic resonance scanner (Siemens Trio Tim, Erlangen, Germany) using a 12-channel head coil (different pattern of brain activity before and after two months of physiotherapeutic program)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nine Hole Peg Test - NHPT</measure>
    <time_frame>2 months</time_frame>
    <description>measure finger dexterity (quicker time means better function)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Paced Auditory Serial Addition Test - PASAT</measure>
    <time_frame>2 months</time_frame>
    <description>The PASAT is a measure of cognitive function that assesses auditory information processing speed and flexibility, as well as calculation ability. The PASAT is presented using audio record to ensure standardization in the rate of stimulus presentation. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. The score for the PASAT is the total number correct out of 60 possible answers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Berg Balance Scale - BBS</measure>
    <time_frame>2 months</time_frame>
    <description>14 items objective measure of static balance and risk of falls (0 the best, 56 the worse)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Timed 25 Foot Walk - T25FW</measure>
    <time_frame>2 months</time_frame>
    <description>The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the patient walk back the same distance. The score for the T25-FW is the average of the two completed trials.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Timed Up and Go - TUG</measure>
    <time_frame>2 months</time_frame>
    <description>The Timed Up and Go test (TUG) is a simple test used to assess a person's mobility and requires both static and dynamic balance. It uses the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">87</enrollment>
  <condition>Neuronal Plasticity</condition>
  <condition>Multiple Sclerosis</condition>
  <condition>Rehabilitation</condition>
  <arm_group>
    <arm_group_label>Motor Program Activating Therapy (MPAT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The MPAT was chosen for our clinical experience - it was developed and verified by our team. In this therapy, patients are corrected into a postural position where the joints are functionally centred. Then somatosensory (manual and verbal) stimuli are applied to activate motor programs in the brain, which then lead to the co-contraction of the patient's whole body when the patient is lying, sitting, standing up or moving forward. Activated programs are repeated under various conditions and in different situations and environments to teach the patients to use the acquired motor skills automatically in daily life.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vojta Reflex Locomotion (VRL)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>VRL was developed by prof. Vojta and is standardly used in the Czech Republic. In this therapy, patients should be set up into the precisely given initial position with defined angular setting of extremities. In each position (supine, prone, lying on the side, and low kneeling position), activation points (zones) are stimulated with precise localization and pressure direction. Such stimulation activates one of the global movement patterns (reflex turning and reflex creeping) corresponding to the initial position. In addition to motor involuntarily reaction, also sensory and autonomic response is activated.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy controls</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>sex and age matched healthy controls</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Motor Program Activating Therapy</intervention_name>
    <description>Patients undergo ambulatory physiotherapy - Motor Program Activating Therapy (2 months, twice a week, 1 hour of duration). Therapy was undertaken at the ambulatory section of the Department of Neurology, Kralovske Vinohrady University Hospital in Prague.</description>
    <arm_group_label>Motor Program Activating Therapy (MPAT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Vojta reflex locomotion</intervention_name>
    <description>Patients undergo ambulatory physiotherapy - Vojta Reflex Locomotion Therapy (2 months, twice a week, 1 hour of duration). Therapy was undertaken at the Department of Rehabilitation and Sport Medicine, Motol University Hospital.</description>
    <arm_group_label>Vojta Reflex Locomotion (VRL)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  definite MS&#xD;
&#xD;
          -  stable clinical status in the preceding 3 months&#xD;
&#xD;
          -  imuno-modulatory treatment for at least two years (including glatiramer acetate,&#xD;
             interferon beta-1a, 1b, mitoxantrone, fingolimod, natulizumab)&#xD;
&#xD;
          -  Expanded Disability Status Scale (EDSS)≤6&#xD;
&#xD;
          -  predominant motor impartment&#xD;
&#xD;
          -  six months or more without any physiotherapy&#xD;
&#xD;
          -  ability to undergo ambulatory physiotherapy&#xD;
&#xD;
        Exlusion criteria:&#xD;
&#xD;
        -other neurological disease or conditions disabling movement&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kamila Řasová, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Third Faculty of Medicine Charles University</affiliation>
  </overall_official>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>June 25, 2020</last_update_submitted>
  <last_update_submitted_qc>June 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Charles University, Czech Republic</investigator_affiliation>
    <investigator_full_name>Kamila Řasová</investigator_full_name>
    <investigator_title>assoc. prof. Kamila Řasová, Ph.D.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</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/NCT04448444
org study id: EK-VP/22/0/2014/2
nct id: NCT04448444
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Imaging methods bring new possibilities for describing the brain plasticity processes that
      underly the improvement of clinical function after physiotherapy in people with multiple
      sclerosis (pwMS). The study determined whether facilitation physiotherapy could enhance brain
      plasticity, compared two facilitation methods, and looked for any relation to clinical
      improvement in pwMS.
The study was designed as parallel group randomized comparison of two kinds of
      physiotherapeutic interventions referred to healthy controls.

      MS patients were examined by fMRI (primary outcomes) and clinical tests (secondary outcomes)
      at the beginning of study. Then, they were randomly divided into two groups (by drawing lots
      in a 1:1 ratio). The first group underwent Vojta reflex locomotion (VRL), and the second
      Motor Program Activating Physiotherapy (MPAT). The length and intensity of treatment was the
      same in both groups (two months, one hour twice a week). After the treatment, a clinical and
      fMRI examination was performed. Healthy volunteers underwent an fMRI examination that was
      considered to be a control.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study was designed as parallel group (outpatients) randomized comparison of two kinds of physiotherapeutic interventions referred to healthy controls.
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Brain activity
time frame: 0 month
description: fMRI examinations on 3T magnetic resonance scanner (Siemens Trio Tim, Erlangen, Germany) using a 12-channel head coil (different pattern of brain activity in healthy and people with MS)
measure: Brain activity
time frame: 0 and 2 months
description: fMRI examinations on 3T magnetic resonance scanner (Siemens Trio Tim, Erlangen, Germany) using a 12-channel head coil (different pattern of brain activity before and after two months of physiotherapeutic program)
measure: Nine Hole Peg Test - NHPT
time frame: 2 months
description: measure finger dexterity (quicker time means better function)
measure: Paced Auditory Serial Addition Test - PASAT
time frame: 2 months
description: The PASAT is a measure of cognitive function that assesses auditory information processing speed and flexibility, as well as calculation ability. The PASAT is presented using audio record to ensure standardization in the rate of stimulus presentation. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. The score for the PASAT is the total number correct out of 60 possible answers.
measure: Berg Balance Scale - BBS
time frame: 2 months
description: 14 items objective measure of static balance and risk of falls (0 the best, 56 the worse)
measure: Timed 25 Foot Walk - T25FW
time frame: 2 months
description: The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the patient walk back the same distance. The score for the T25-FW is the average of the two completed trials.
measure: Timed Up and Go - TUG
time frame: 2 months
description: The Timed Up and Go test (TUG) is a simple test used to assess a person's mobility and requires both static and dynamic balance. It uses the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down.
arm group label: Motor Program Activating Therapy (MPAT)
arm group type: Experimental
description: The MPAT was chosen for our clinical experience - it was developed and verified by our team. In this therapy, patients are corrected into a postural position where the joints are functionally centred. Then somatosensory (manual and verbal) stimuli are applied to activate motor programs in the brain, which then lead to the co-contraction of the patient's whole body when the patient is lying, sitting, standing up or moving forward. Activated programs are repeated under various conditions and in different situations and environments to teach the patients to use the acquired motor skills automatically in daily life.
arm group label: Vojta Reflex Locomotion (VRL)
arm group type: Experimental
description: VRL was developed by prof. Vojta and is standardly used in the Czech Republic. In this therapy, patients should be set up into the precisely given initial position with defined angular setting of extremities. In each position (supine, prone, lying on the side, and low kneeling position), activation points (zones) are stimulated with precise localization and pressure direction. Such stimulation activates one of the global movement patterns (reflex turning and reflex creeping) corresponding to the initial position. In addition to motor involuntarily reaction, also sensory and autonomic response is activated.
arm group label: healthy controls
arm group type: No Intervention
description: sex and age matched healthy controls
intervention type: Behavioral
intervention name: Motor Program Activating Therapy
description: Patients undergo ambulatory physiotherapy - Motor Program Activating Therapy (2 months, twice a week, 1 hour of duration). Therapy was undertaken at the ambulatory section of the Department of Neurology, Kralovske Vinohrady University Hospital in Prague.
arm group label: Motor Program Activating Therapy (MPAT)
intervention type: Behavioral
intervention name: Vojta reflex locomotion
description: Patients undergo ambulatory physiotherapy - Vojta Reflex Locomotion Therapy (2 months, twice a week, 1 hour of duration). Therapy was undertaken at the Department of Rehabilitation and Sport Medicine, Motol University Hospital.
arm group label: Vojta Reflex Locomotion (VRL)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kamila Řasová, Ph.D.
role: Principal Investigator
affiliation: Third Faculty of Medicine Charles University
responsible party type: Principal Investigator
investigator affiliation: Charles University, Czech Republic
investigator full name: Kamila Řasová
investigator title: assoc. prof. Kamila Řasová, Ph.D.
mesh term: Multiple Sclerosis
mesh term: Sclerosis