<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/NCT03249155</url>
  </required_header>
  <id_info>
    <org_study_id>UTrieste</org_study_id>
    <nct_id>NCT03249155</nct_id>
  </id_info>
  <brief_title>Action Observation Plus Sonification Therapeutic Protocol</brief_title>
  <acronym>AOFREEPD</acronym>
  <official_title>Action Observation Plus Sonification. A Novel Therapeutic Protocol for Parkinson's Patient With Freezing of Gait</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Trieste</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Trieste</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>
      The target of this clinical trial is Freezing of Gait symptom (FoG), and associated falls.&#xD;
      The project is aimed to evaluate the effects of an innovative experimental protocol to treat&#xD;
      Parkinson (PD) Patients with FoG. This new physiotherapy protocol is based on the recovery of&#xD;
      the correct mental representation of the movement, through Action Observation. A method that&#xD;
      can facilitate the process of re-learning correct motor strategies, and at the same time&#xD;
      avoid the phenomena of external cues dependency. Our version of the Action observation method&#xD;
      uses video-clips of gait exercises. In these video-clips the audio part was obtained with the&#xD;
      sonification of the kinematics of the body movements. We postulate that action observation,&#xD;
      through the activation of the mirror system, is able to reactivate stored motor programs&#xD;
      concerning walking ability, which can be used to facilitate recovery of defective motor&#xD;
      control and overcome freezing of gait. Moreover, given that patients with PD and FoG may have&#xD;
      major shortages of attention resources, a multisensory approach (audio-visual) would help to&#xD;
      further reduce the attention load, facilitating learning processes. Therefore half of&#xD;
      participants received an experimental protocol with Action Observation plus signification&#xD;
      while the other half received a traditional protocol combining visual and auditory cues.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      FoG is a disabling and distressing symptom strictly associated to falls. The little or no&#xD;
      pharmacological responsiveness of FoG has led to an increasing interest in rehabilitation&#xD;
      interventions aimed at functional recovery and autonomy. Currently, standard protocols&#xD;
      employed for rehabilitation are based on the use of external (visual and auditory) sensory&#xD;
      cues. However, cued strategies generate an important dependence on the environment. Teaching&#xD;
      motor strategies without cues (i.e. action observation - AO) can be an alternative/innovative&#xD;
      approach to rehabilitation, that matters most on appropriate allocation of attention and&#xD;
      lightening cognitive load. One way to increase the effectiveness of AO, is the use of a&#xD;
      multisensory learning mode (visual and auditory) to facilitate the recovery of motor gestures&#xD;
      thanks to enhanced perceptual processes, which is known to be reduced in PD with FoG.&#xD;
      Sonification could be an important method to enhance therapeutical effects in action&#xD;
      observation rehabilitation process. Sonification of movements amplifies the activity of the&#xD;
      human action observation system including subcortical structures of the motor loop.&#xD;
&#xD;
      Methods. We compared the effects of two different therapeutic protocols. The experimental&#xD;
      protocol was based on action observation plus sonification; patients of the experimental&#xD;
      group re-learned 8 motor gestures watching video-clips showing an actor performing the same&#xD;
      gestures, and then tried to repeat the gesture. Each video-clip was composed by images and&#xD;
      sounds of the gestures. The sounds of gestures were obtained with the sonification technique,&#xD;
      by transforming kinematic data (velocity) recorded during the execution of gesture, into&#xD;
      pitch variations (for an example see: bit.ly/sonif_example). The same 8 motor gestures were&#xD;
      re-learned in the standard protocol, with a common sensory stimulation method (active&#xD;
      comparator group). We evaluated all patients of the two groups with functional and clinical&#xD;
      scales before, immediately after, at 1 month, and 3 months after each treatment.The duration&#xD;
      of each protocol will be about 2 months, 15 sessions, 2 times a week.&#xD;
&#xD;
      Data Safety Monitoring Plan. The patients' assignment to the two groups was as follow: a list&#xD;
      of 20 patients (10 patients for each group) was created and the order fully randomized. The&#xD;
      list was filled with the patients following the order of arrival from the Neurology Clinic&#xD;
      (Cattinara Hospital, Trieste). All the evaluations (neuropsychological, neurological, and&#xD;
      physiotherapy) are blind respect to the patient's group assignment. The person in charge to&#xD;
      make assignment patient-treatment will not be the PI.&#xD;
&#xD;
      Sample size calculation. The dependent variable (the primary outcome measure) is the score of&#xD;
      the N-FOG Questionnaire. Sample size has been calculated considering a repeated measures&#xD;
      mixed ANOVA of the primary outcome measure, with the software G*Power 3. The result gives a&#xD;
      sample size of 20 patients: 10 for each group (experimental and active comparator group). The&#xD;
      sizing of the sample is justified by similar protocols evaluations that with an identical&#xD;
      sample size (n = 10 per group) found statistically significant results.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2, 2015</start_date>
  <completion_date type="Actual">July 3, 2017</completion_date>
  <primary_completion_date type="Actual">July 3, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>(Changes in) New Freezing of Gait Questionnaire - NFOG-Q</measure>
    <time_frame>Before treatment, 2-months (end of treatment), 3-months, and 5-months</time_frame>
    <description>Clinical Administered Questionnaire</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>(Changes in) Unified Parkinson Disease Rating Scale - part 2, 3</measure>
    <time_frame>Before treatment, 2-months (end of treatment), 3-months, and 5-months</time_frame>
    <description>Clinical Administered Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Changes in) BERG Balance Scale</measure>
    <time_frame>Before treatment, 2-months (end of treatment), 3-months, and 5-months</time_frame>
    <description>Clinical Administered Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Changes in) MPAS - Modified Parkinson Assessment Scale</measure>
    <time_frame>Before treatment, 2-months (end of treatment), 3-months, and 5-months</time_frame>
    <description>Clinical Administered Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Changes in) TUG - Time Up and Go</measure>
    <time_frame>Before treatment, 2-months (end of treatment), 3-months, and 5-months</time_frame>
    <description>Clinical Administered Test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Changes in) 6MWT - Six Minutes Walking Test</measure>
    <time_frame>Before treatment, 2-months (end of treatment), 3-months, and 5-months</time_frame>
    <description>Clinical Administered Test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>(Changes in) PDQ-39 - Parkinson Disease Quality of Life Questionnaire</measure>
    <time_frame>Before treatment, 2-months (end of treatment), 3-months, and 5-months</time_frame>
    <description>39 Items Self Administered Questionnaire</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>AO - plus sonification</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients re-learn 8 motor gestures watching video-clips showing an actor performing the same gestures, and then tried to repeat the gesture.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CUE - visual and auditory</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients re-learn 8 motor gestures practicing a traditional protocol combining visual and auditory cues.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>AO - plus sonification</intervention_name>
    <description>patients re-learn 8 motor gestures watching video-clips showing an actor performing the same gestures, and then tried to repeat the gesture. Each video-clip is composed by images and sounds of the gestures. The sound of gestures is obtained with the sonification technique, by transforming kinematic data (velocity) recorded during the execution of gesture, into pitch variations (for an example see: bit.ly/sonif_example)</description>
    <arm_group_label>AO - plus sonification</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>CUE - visual and auditory</intervention_name>
    <description>patients re-learned 8 motor gestures practicing a traditional protocol combining visual and auditory cues</description>
    <arm_group_label>CUE - visual and auditory</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Parkinson's Disease Diagnosis (UK Brain Bank)&#xD;
&#xD;
          -  H&amp;R stage &lt; or = to 3;&#xD;
&#xD;
          -  score of 1 on the 1st question of the NFOG-Q;&#xD;
&#xD;
          -  no comorbidities that would preclude physiotherapy treatment;&#xD;
&#xD;
          -  Back Depression Scale score &lt; or = to 16;&#xD;
&#xD;
          -  stabilized pharmacological therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  dementia: MMSE &gt; or = to 24&#xD;
&#xD;
          -  past neuropathies, ictus or myelopathies&#xD;
&#xD;
          -  orthopaedic comorbidity that may impede walking&#xD;
&#xD;
          -  presence of DBS&#xD;
&#xD;
          -  severe psychiatric pathology&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paolo Bernardis, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Trieste</affiliation>
  </overall_official>
  <reference>
    <citation>Pelosin E, Avanzino L, Bove M, Stramesi P, Nieuwboer A, Abbruzzese G. Action observation improves freezing of gait in patients with Parkinson's disease. Neurorehabil Neural Repair. 2010 Oct;24(8):746-52. doi: 10.1177/1545968310368685. Epub 2010 May 7.</citation>
    <PMID>20453155</PMID>
  </reference>
  <reference>
    <citation>Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.</citation>
    <PMID>17695343</PMID>
  </reference>
  <reference>
    <citation>Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. 2011 Aug;10(8):734-44. doi: 10.1016/S1474-4422(11)70143-0.</citation>
    <PMID>21777828</PMID>
  </reference>
  <reference>
    <citation>Patla AE, Vickers JN. Where and when do we look as we approach and step over an obstacle in the travel path? Neuroreport. 1997 Dec 1;8(17):3661-5. doi: 10.1097/00001756-199712010-00002.</citation>
    <PMID>9427347</PMID>
  </reference>
  <reference>
    <citation>Stefan K, Cohen LG, Duque J, Mazzocchio R, Celnik P, Sawaki L, Ungerleider L, Classen J. Formation of a motor memory by action observation. J Neurosci. 2005 Oct 12;25(41):9339-46. doi: 10.1523/JNEUROSCI.2282-05.2005.</citation>
    <PMID>16221842</PMID>
  </reference>
  <reference>
    <citation>Vinken PM, Kroger D, Fehse U, Schmitz G, Brock H, Effenberg AO. Auditory coding of human movement kinematics. Multisens Res. 2013;26(6):533-52. doi: 10.1163/22134808-00002435. Erratum In: Multisens Res. 2014;27(3-4):263-4.</citation>
    <PMID>24800411</PMID>
  </reference>
  <reference>
    <citation>Schmitz G, Mohammadi B, Hammer A, Heldmann M, Samii A, Munte TF, Effenberg AO. Observation of sonified movements engages a basal ganglia frontocortical network. BMC Neurosci. 2013 Mar 14;14:32. doi: 10.1186/1471-2202-14-32.</citation>
    <PMID>23496827</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>August 10, 2017</last_update_submitted>
  <last_update_submitted_qc>August 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Trieste</investigator_affiliation>
    <investigator_full_name>Paolo Bernardis</investigator_full_name>
    <investigator_title>Phd</investigator_title>
  </responsible_party>
  <keyword>Freezing of Gait, Action Observation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</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/NCT03249155
org study id: UTrieste
nct id: NCT03249155
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The target of this clinical trial is Freezing of Gait symptom (FoG), and associated falls.
      The project is aimed to evaluate the effects of an innovative experimental protocol to treat
      Parkinson (PD) Patients with FoG. This new physiotherapy protocol is based on the recovery of
      the correct mental representation of the movement, through Action Observation. A method that
      can facilitate the process of re-learning correct motor strategies, and at the same time
      avoid the phenomena of external cues dependency. Our version of the Action observation method
      uses video-clips of gait exercises. In these video-clips the audio part was obtained with the
      sonification of the kinematics of the body movements. We postulate that action observation,
      through the activation of the mirror system, is able to reactivate stored motor programs
      concerning walking ability, which can be used to facilitate recovery of defective motor
      control and overcome freezing of gait. Moreover, given that patients with PD and FoG may have
      major shortages of attention resources, a multisensory approach (audio-visual) would help to
      further reduce the attention load, facilitating learning processes. Therefore half of
      participants received an experimental protocol with Action Observation plus signification
      while the other half received a traditional protocol combining visual and auditory cues.
FoG is a disabling and distressing symptom strictly associated to falls. The little or no
      pharmacological responsiveness of FoG has led to an increasing interest in rehabilitation
      interventions aimed at functional recovery and autonomy. Currently, standard protocols
      employed for rehabilitation are based on the use of external (visual and auditory) sensory
      cues. However, cued strategies generate an important dependence on the environment. Teaching
      motor strategies without cues (i.e. action observation - AO) can be an alternative/innovative
      approach to rehabilitation, that matters most on appropriate allocation of attention and
      lightening cognitive load. One way to increase the effectiveness of AO, is the use of a
      multisensory learning mode (visual and auditory) to facilitate the recovery of motor gestures
      thanks to enhanced perceptual processes, which is known to be reduced in PD with FoG.
      Sonification could be an important method to enhance therapeutical effects in action
      observation rehabilitation process. Sonification of movements amplifies the activity of the
      human action observation system including subcortical structures of the motor loop.

      Methods. We compared the effects of two different therapeutic protocols. The experimental
      protocol was based on action observation plus sonification; patients of the experimental
      group re-learned 8 motor gestures watching video-clips showing an actor performing the same
      gestures, and then tried to repeat the gesture. Each video-clip was composed by images and
      sounds of the gestures. The sounds of gestures were obtained with the sonification technique,
      by transforming kinematic data (velocity) recorded during the execution of gesture, into
      pitch variations (for an example see: bit.ly/sonif_example). The same 8 motor gestures were
      re-learned in the standard protocol, with a common sensory stimulation method (active
      comparator group). We evaluated all patients of the two groups with functional and clinical
      scales before, immediately after, at 1 month, and 3 months after each treatment.The duration
      of each protocol will be about 2 months, 15 sessions, 2 times a week.

      Data Safety Monitoring Plan. The patients' assignment to the two groups was as follow: a list
      of 20 patients (10 patients for each group) was created and the order fully randomized. The
      list was filled with the patients following the order of arrival from the Neurology Clinic
      (Cattinara Hospital, Trieste). All the evaluations (neuropsychological, neurological, and
      physiotherapy) are blind respect to the patient's group assignment. The person in charge to
      make assignment patient-treatment will not be the PI.

      Sample size calculation. The dependent variable (the primary outcome measure) is the score of
      the N-FOG Questionnaire. Sample size has been calculated considering a repeated measures
      mixed ANOVA of the primary outcome measure, with the software G*Power 3. The result gives a
      sample size of 20 patients: 10 for each group (experimental and active comparator group). The
      sizing of the sample is justified by similar protocols evaluations that with an identical
      sample size (n = 10 per group) found statistically significant results.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Care Provider, Investigator, Outcomes Assessor)
measure: (Changes in) New Freezing of Gait Questionnaire - NFOG-Q
time frame: Before treatment, 2-months (end of treatment), 3-months, and 5-months
description: Clinical Administered Questionnaire
measure: (Changes in) Unified Parkinson Disease Rating Scale - part 2, 3
time frame: Before treatment, 2-months (end of treatment), 3-months, and 5-months
description: Clinical Administered Scale
measure: (Changes in) BERG Balance Scale
time frame: Before treatment, 2-months (end of treatment), 3-months, and 5-months
description: Clinical Administered Scale
measure: (Changes in) MPAS - Modified Parkinson Assessment Scale
time frame: Before treatment, 2-months (end of treatment), 3-months, and 5-months
description: Clinical Administered Scale
measure: (Changes in) TUG - Time Up and Go
time frame: Before treatment, 2-months (end of treatment), 3-months, and 5-months
description: Clinical Administered Test
measure: (Changes in) 6MWT - Six Minutes Walking Test
time frame: Before treatment, 2-months (end of treatment), 3-months, and 5-months
description: Clinical Administered Test
measure: (Changes in) PDQ-39 - Parkinson Disease Quality of Life Questionnaire
time frame: Before treatment, 2-months (end of treatment), 3-months, and 5-months
description: 39 Items Self Administered Questionnaire
arm group label: AO - plus sonification
arm group type: Experimental
description: patients re-learn 8 motor gestures watching video-clips showing an actor performing the same gestures, and then tried to repeat the gesture.
arm group label: CUE - visual and auditory
arm group type: Active Comparator
description: patients re-learn 8 motor gestures practicing a traditional protocol combining visual and auditory cues.
intervention type: Behavioral
intervention name: AO - plus sonification
description: patients re-learn 8 motor gestures watching video-clips showing an actor performing the same gestures, and then tried to repeat the gesture. Each video-clip is composed by images and sounds of the gestures. The sound of gestures is obtained with the sonification technique, by transforming kinematic data (velocity) recorded during the execution of gesture, into pitch variations (for an example see: bit.ly/sonif_example)
arm group label: AO - plus sonification
intervention type: Behavioral
intervention name: CUE - visual and auditory
description: patients re-learned 8 motor gestures practicing a traditional protocol combining visual and auditory cues
arm group label: CUE - visual and auditory
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Paolo Bernardis, PhD
role: Principal Investigator
affiliation: University of Trieste
citation: Pelosin E, Avanzino L, Bove M, Stramesi P, Nieuwboer A, Abbruzzese G. Action observation improves freezing of gait in patients with Parkinson's disease. Neurorehabil Neural Repair. 2010 Oct;24(8):746-52. doi: 10.1177/1545968310368685. Epub 2010 May 7.
PMID: 20453155
citation: Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.
PMID: 17695343
citation: Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. 2011 Aug;10(8):734-44. doi: 10.1016/S1474-4422(11)70143-0.
PMID: 21777828
citation: Patla AE, Vickers JN. Where and when do we look as we approach and step over an obstacle in the travel path? Neuroreport. 1997 Dec 1;8(17):3661-5. doi: 10.1097/00001756-199712010-00002.
PMID: 9427347
citation: Stefan K, Cohen LG, Duque J, Mazzocchio R, Celnik P, Sawaki L, Ungerleider L, Classen J. Formation of a motor memory by action observation. J Neurosci. 2005 Oct 12;25(41):9339-46. doi: 10.1523/JNEUROSCI.2282-05.2005.
PMID: 16221842
citation: Vinken PM, Kroger D, Fehse U, Schmitz G, Brock H, Effenberg AO. Auditory coding of human movement kinematics. Multisens Res. 2013;26(6):533-52. doi: 10.1163/22134808-00002435. Erratum In: Multisens Res. 2014;27(3-4):263-4.
PMID: 24800411
citation: Schmitz G, Mohammadi B, Hammer A, Heldmann M, Samii A, Munte TF, Effenberg AO. Observation of sonified movements engages a basal ganglia frontocortical network. BMC Neurosci. 2013 Mar 14;14:32. doi: 10.1186/1471-2202-14-32.
PMID: 23496827
responsible party type: Principal Investigator
investigator affiliation: University of Trieste
investigator full name: Paolo Bernardis
investigator title: Phd
mesh term: Parkinson Disease