<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/NCT04435301</url>
  </required_header>
  <id_info>
    <org_study_id>Oscillatory stimulation</org_study_id>
    <nct_id>NCT04435301</nct_id>
  </id_info>
  <brief_title>Oscillatory Acoustic-electric Stimulation in Patients With Disorders of Consciousness</brief_title>
  <official_title>Acoustic-electric Therapy in Patients With Disorders of Consciousness</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Affiliated Hospital of Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Maastricht University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhejiang Mingzhou Brain Rehabilitation Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>First Affiliated Hospital of Zhejiang 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>
      Altered gamma activity has been observed in several neurological and psychiatric disorders,&#xD;
      including a reduction in gamma synchronization in patients with disorders of consciousness.&#xD;
      Modulation of gamma oscillations with rhythmic stimulation has been used as a possible&#xD;
      therapeutic tool. Hence, we try to use acoustic and electric stimulation at gamma frequency&#xD;
      to restore brain oscillation and thereby to improve conscious awareness in patients with&#xD;
      disorders of consciousness.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We propose a matched-pair parallel study in patients with disorders of consciousness to&#xD;
      investigate whether combined acoustic and trigeminal nerve stimulation can modulate brain&#xD;
      oscillations, as measured by electroencephalography (EEG), and whether the brain activity&#xD;
      changes are coupled with improvements in consciousness.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 20, 2020</start_date>
  <completion_date type="Actual">September 20, 2021</completion_date>
  <primary_completion_date type="Actual">September 20, 2021</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 (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Coma Recovery Scale-Revised scores</measure>
    <time_frame>Day 1-5, Day 11-15</time_frame>
    <description>Coma Recovery Scale-Revised(CRS-R) scores are the gold standard for consciousness. CRS-R consists of 23 items, grouped into 6 sub-scales: auditory, visual, motor, oromotor, communication and arousal. The lowest score on each sub-scale represents reflexive activity; the highest represents behaviors mediated by cognitive input. The total score ranges between 0 (worst) and 23 (best).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neuropsychological assessment</measure>
    <time_frame>Day 5 and Day 11</time_frame>
    <description>EEG indicators could be used to assess the conscious level, including gamma oscillations and event-related potentials(P300).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Glasgow Outcome Scale-Extended</measure>
    <time_frame>1 year after stimulation</time_frame>
    <description>A widely used index for outcomes after brain injury</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">73</enrollment>
  <condition>Consciousness Disorder</condition>
  <arm_group>
    <arm_group_label>Gamma modulation effect</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>40Hz current is applied by a battery-driven current stimulator(NeuroConn, Germany). Two pairs of electrodes are attached to the middle and lower part of the face to stimulate the maxillary nerve (V2) and the mandibular nerve (V3), respectively. 40Hz acoustic stimuli and 40Hz electric stimuli are synchronously applied for 40min/day, for a total of 5 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Beta modulation effect</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>28Hz current is applied by a battery-driven current stimulator. Two pairs of electrodes are attached to the middle and lower part of the face to stimulate the maxillary nerve (V2) and the mandibular nerve (V3). 28Hz acoustic stimuli and 28Hz electric stimuli are synchronously applied for 40min/day, for a total of 5 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham modulation group</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham stimulation was identical to the 40Hz stimulation, except that the acoustic and electric stimulation were ramped down after 0.5 min to remain turned off for the remaining 39.5 min. Sham stimuli are applied for 40min/day, for a total of 5 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>DC-Stimulator, NeuroConn, Germany</intervention_name>
    <description>Neurostimulation device</description>
    <arm_group_label>Beta modulation effect</arm_group_label>
    <arm_group_label>Gamma modulation effect</arm_group_label>
    <arm_group_label>Sham modulation group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of disorders of consciousness based on CRS-R&#xD;
&#xD;
          -  Time post-injury ranging from one to twelve months&#xD;
&#xD;
          -  No history of acquired brain injury or psychiatric or neurological diseases&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not medically stable&#xD;
&#xD;
          -  Any contraindication to electric stimulation&#xD;
&#xD;
          -  Hearing impairment before brain injury&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Benyan Luo</last_name>
    <role>Study Director</role>
    <affiliation>The First Affiliated Hospital, Zhejiang University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>First Affiliated Hospital,Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Fan S, Wu X, Xie M, Li X, Liu C, Su Y, Chen Y, Wu S, Ma C. Trigeminal nerve stimulation successfully awakened an unconscious patient. Brain Stimul. 2019 Mar-Apr;12(2):361-363. doi: 10.1016/j.brs.2018.11.001. Epub 2018 Nov 3. No abstract available.</citation>
    <PMID>30448386</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>November 18, 2021</last_update_submitted>
  <last_update_submitted_qc>November 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>disorders of consciousness</keyword>
  <keyword>electric stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Consciousness Disorders</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/NCT04435301
org study id: Oscillatory stimulation
nct id: NCT04435301
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Altered gamma activity has been observed in several neurological and psychiatric disorders,
      including a reduction in gamma synchronization in patients with disorders of consciousness.
      Modulation of gamma oscillations with rhythmic stimulation has been used as a possible
      therapeutic tool. Hence, we try to use acoustic and electric stimulation at gamma frequency
      to restore brain oscillation and thereby to improve conscious awareness in patients with
      disorders of consciousness.
We propose a matched-pair parallel study in patients with disorders of consciousness to
      investigate whether combined acoustic and trigeminal nerve stimulation can modulate brain
      oscillations, as measured by electroencephalography (EEG), and whether the brain activity
      changes are coupled with improvements in consciousness.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Coma Recovery Scale-Revised scores
time frame: Day 1-5, Day 11-15
description: Coma Recovery Scale-Revised(CRS-R) scores are the gold standard for consciousness. CRS-R consists of 23 items, grouped into 6 sub-scales: auditory, visual, motor, oromotor, communication and arousal. The lowest score on each sub-scale represents reflexive activity; the highest represents behaviors mediated by cognitive input. The total score ranges between 0 (worst) and 23 (best).
measure: Neuropsychological assessment
time frame: Day 5 and Day 11
description: EEG indicators could be used to assess the conscious level, including gamma oscillations and event-related potentials(P300).
measure: Glasgow Outcome Scale-Extended
time frame: 1 year after stimulation
description: A widely used index for outcomes after brain injury
arm group label: Gamma modulation effect
arm group type: Experimental
description: 40Hz current is applied by a battery-driven current stimulator(NeuroConn, Germany). Two pairs of electrodes are attached to the middle and lower part of the face to stimulate the maxillary nerve (V2) and the mandibular nerve (V3), respectively. 40Hz acoustic stimuli and 40Hz electric stimuli are synchronously applied for 40min/day, for a total of 5 days.
arm group label: Beta modulation effect
arm group type: Experimental
description: 28Hz current is applied by a battery-driven current stimulator. Two pairs of electrodes are attached to the middle and lower part of the face to stimulate the maxillary nerve (V2) and the mandibular nerve (V3). 28Hz acoustic stimuli and 28Hz electric stimuli are synchronously applied for 40min/day, for a total of 5 days.
arm group label: Sham modulation group
arm group type: Sham Comparator
description: Sham stimulation was identical to the 40Hz stimulation, except that the acoustic and electric stimulation were ramped down after 0.5 min to remain turned off for the remaining 39.5 min. Sham stimuli are applied for 40min/day, for a total of 5 days.
intervention type: Device
intervention name: DC-Stimulator, NeuroConn, Germany
description: Neurostimulation device
arm group label: Beta modulation effect
arm group label: Gamma modulation effect
arm group label: Sham modulation group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Benyan Luo
role: Study Director
affiliation: The First Affiliated Hospital, Zhejiang University
facility: 
country: China
citation: Fan S, Wu X, Xie M, Li X, Liu C, Su Y, Chen Y, Wu S, Ma C. Trigeminal nerve stimulation successfully awakened an unconscious patient. Brain Stimul. 2019 Mar-Apr;12(2):361-363. doi: 10.1016/j.brs.2018.11.001. Epub 2018 Nov 3. No abstract available.
PMID: 30448386
responsible party type: Sponsor
mesh term: Consciousness Disorders
sharing ipd: No