<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/NCT04421365</url>
  </required_header>
  <id_info>
    <org_study_id>2019P001547</org_study_id>
    <nct_id>NCT04421365</nct_id>
  </id_info>
  <brief_title>Brain-Computer Interfaces in Laryngeal Dystonia</brief_title>
  <official_title>Adaptive Closed-loop Brain-computer Interface Therapeutic Intervention in Laryngeal Dystonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts Eye and Ear Infirmary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts Eye and Ear Infirmary</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The researchers will develop and evaluate the use of adaptive closed-loop brain-computer&#xD;
      interface therapeutic intervention in laryngeal dystonia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dystonia is a neurological disorder, which causes involuntary, sustained muscle contractions,&#xD;
      resulting in uncontrollable twisting, repetitive movements, and abnormal postures. Selective&#xD;
      impairment of motor control of highly skilled and goal-oriented behaviors is the defining&#xD;
      feature of task-specific focal dystonias. Among these, laryngeal dystonia (LD) is&#xD;
      characterized by involuntary spasms in laryngeal muscles, which selectively occur during&#xD;
      speaking but not whispering, crying, or laughing. As speech communication is a vital part of&#xD;
      our daily existence, LD symptoms have a deeply pervasive effect on the quality of life of the&#xD;
      affected individual, often extending beyond speech motor deficits and causing significant&#xD;
      occupational disability, psychiatric comorbidities, long-lasting stress, and social&#xD;
      isolation.&#xD;
&#xD;
      Despite the chronic, debilitating impact of LD, its clinical management remains stagnant. The&#xD;
      overall objective of this study is to conduct a randomized, sham-controlled, parallel design,&#xD;
      phase 1 clinical trial to assess the feasibility and efficacy of a neurofeedback&#xD;
      brain-computer interface (BCI) paradigm in LD patients that acts upon and modulates the&#xD;
      disorder pathophysiology. The rationale for the proposed studies is that delineation of&#xD;
      task-specific neural alterations for their feasible utilization as a pathophysiological&#xD;
      target of therapeutic intervention will establish a robust scientific foundation for the&#xD;
      development of novel strategies for LD treatment, inform the conduct of the next phase of the&#xD;
      clinical trial, and directly contribute to closing the existing critical gap in the clinical&#xD;
      management of this disorder.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 18, 2022</start_date>
  <completion_date type="Anticipated">August 31, 2026</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2026</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>Patients will be assigned to active neurofeedback BCI and sham neurofeedback BCI groups to assess the feasibility of the BCI system and the efficacy of neurofeedback.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in voice symptoms</measure>
    <time_frame>At the end of day 5 of the intervention</time_frame>
    <description>Change in the number of dystonic voice breaks as the result of active neurofeedback BCI intervention assessed using perceptual voice analysis</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Laryngeal Dystonia</condition>
  <arm_group>
    <arm_group_label>Active neurofeedback BCI</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients are presented with symptomatic speech and asymptomatic whisper and, using active EEG-based neurofeedback, are trained to correct their speech by matching their brain patterns to those of whisper. This training is expected to be effective for symptom improvement.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham neurofeedback BCI</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Patients are presented with symptomatic speech and asymptomatic whisper and, using sham EEG-based neurofeedback, are trained to correct their speech by matching their brain patterns to those of whisper. This training is expected not to be effective for symptom improvement.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>neurofeedback brain-computer interface (BCI)</intervention_name>
    <description>The integrated components of BCI system include the high-density EEG, 3D-VR, and a built-in ML platform as a real-time neural signal decoder and neurofeedback controller.</description>
    <arm_group_label>Active neurofeedback BCI</arm_group_label>
    <arm_group_label>Sham neurofeedback BCI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Patients will have clinically documented isolated adductor laryngeal dystonia (ADLD)&#xD;
             without any other forms of dystonia or tremor. ADLD causes involuntary spasms during&#xD;
             vocal fold adduction, leading to voice breaks predominantly on vowels and strained,&#xD;
             strangles quality of voice, predominantly affecting voice production during the&#xD;
             speaking. Only patients with the ADLD form of disorder will be recruited to minimize&#xD;
             the impact of heterogeneity of voice symptomatology on the outcome of these phase 1&#xD;
             studies;&#xD;
&#xD;
          2. Healthy controls will be healthy individuals with a negative history of any&#xD;
             neurological, psychiatric, or laryngeal problems;&#xD;
&#xD;
          3. Age from 18 to 80 years;&#xD;
&#xD;
          4. Native English speakers. Non-English-speaking subjects will not be recruited because&#xD;
             brain activation and neural network organization are different between native and&#xD;
             non-native English speakers;&#xD;
&#xD;
          5. Right-handedness (based on Edinburgh Handedness Inventory). Left-handed subjects will&#xD;
             not be recruited because brain activation and neural network organization are&#xD;
             different between right and left-handed individuals;&#xD;
&#xD;
          6. Normal cognitive status (based on Montreal Cognitive Assessment).&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Subjects who are incapable of giving informed consent will be excluded from the study;&#xD;
&#xD;
          2. Pregnant or breastfeeding women until the time they are no longer pregnant or&#xD;
             breastfeeding will be excluded from the study. All women of childbearing potential&#xD;
             will undergo a urine pregnancy test, which must be negative for study participation;&#xD;
&#xD;
          3. Subjects with a past or present medical history of (a) neurological problems, such as&#xD;
             stroke, movement disorders (except for ADLD in the patient group), brain tumors,&#xD;
             ataxias, myopathies, myasthenia gravis, demyelinating diseases; (b) psychiatric&#xD;
             problems, such as schizophrenia, bipolar depression, obsessive-compulsive disorder;&#xD;
             (c) laryn¬geal problems, such as vocal fold paralysis, paresis, carcinoma;&#xD;
&#xD;
          4. Subjects with impaired hearing, vision, and speaking abilities (except for ADLD), as&#xD;
             these would most typically have a neurological origin;&#xD;
&#xD;
          5. Patients who have dystonia symptoms at rest in order to avoid the potential confound&#xD;
             of dystonic spasms occurring during the asymptomatic task production;&#xD;
&#xD;
          6. Patients who are not symptomatic due to the treatment with botulinum toxin injections&#xD;
             into the affected muscles. The duration of positive effects of botulinum toxin varies&#xD;
             from patient to patient but lasts on average for 3-4 months. All patients will be&#xD;
             evaluated to ensure that they are fully symptomatic and are at least three months&#xD;
             post-injection prior to study participation;&#xD;
&#xD;
          7. To avoid the possibility of confounding effects of drugs acting upon the central&#xD;
             nervous system, all subjects will be questioned about any prescribed or&#xD;
             over-the-counter medications as part of their initial screening. Those who are on&#xD;
             medication(s) affecting the central nervous system will be excluded;&#xD;
&#xD;
          8. Subjects with implanted deep brain stimulators will be excluded from the study;&#xD;
&#xD;
          9. Subjects will be asked whether they have undergone any head and neck surgeries,&#xD;
             particularly any brain surgery and laryngeal surgeries, such as thyroplasty, laryngeal&#xD;
             denervation, and selective laryngeal adductor denervation-reinnervation. Because both&#xD;
             brain and laryngeal surgery may potentially lead to the brain structure and function&#xD;
             re-organization, all subjects with a history of brain and/or laryngeal surgery will be&#xD;
             excluded from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kristina Simonyan, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts Eye and Ear</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kristina Simonyan, MD, PhD</last_name>
    <phone>617-573-6016</phone>
    <email>simonyan_lab@meei.harvard.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Massachusetts Eye and Ear Infirmary</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristina Simonyan, MD, PhD</last_name>
      <phone>617-573-6016</phone>
      <email>simonyan_lab@meei.harvard.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>August 10, 2022</last_update_submitted>
  <last_update_submitted_qc>August 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts Eye and Ear Infirmary</investigator_affiliation>
    <investigator_full_name>Kristina Simonyan</investigator_full_name>
    <investigator_title>Associate Professor of Otolaryngology - Head and Neck Surgery</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dysphonia</mesh_term>
    <mesh_term>Dystonia</mesh_term>
    <mesh_term>Dystonic 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/NCT04421365
org study id: 2019P001547
nct id: NCT04421365
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The researchers will develop and evaluate the use of adaptive closed-loop brain-computer
      interface therapeutic intervention in laryngeal dystonia.
Dystonia is a neurological disorder, which causes involuntary, sustained muscle contractions,
      resulting in uncontrollable twisting, repetitive movements, and abnormal postures. Selective
      impairment of motor control of highly skilled and goal-oriented behaviors is the defining
      feature of task-specific focal dystonias. Among these, laryngeal dystonia (LD) is
      characterized by involuntary spasms in laryngeal muscles, which selectively occur during
      speaking but not whispering, crying, or laughing. As speech communication is a vital part of
      our daily existence, LD symptoms have a deeply pervasive effect on the quality of life of the
      affected individual, often extending beyond speech motor deficits and causing significant
      occupational disability, psychiatric comorbidities, long-lasting stress, and social
      isolation.

      Despite the chronic, debilitating impact of LD, its clinical management remains stagnant. The
      overall objective of this study is to conduct a randomized, sham-controlled, parallel design,
      phase 1 clinical trial to assess the feasibility and efficacy of a neurofeedback
      brain-computer interface (BCI) paradigm in LD patients that acts upon and modulates the
      disorder pathophysiology. The rationale for the proposed studies is that delineation of
      task-specific neural alterations for their feasible utilization as a pathophysiological
      target of therapeutic intervention will establish a robust scientific foundation for the
      development of novel strategies for LD treatment, inform the conduct of the next phase of the
      clinical trial, and directly contribute to closing the existing critical gap in the clinical
      management of this disorder.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be assigned to active neurofeedback BCI and sham neurofeedback BCI groups to assess the feasibility of the BCI system and the efficacy of neurofeedback.
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Changes in voice symptoms
time frame: At the end of day 5 of the intervention
description: Change in the number of dystonic voice breaks as the result of active neurofeedback BCI intervention assessed using perceptual voice analysis
arm group label: Active neurofeedback BCI
arm group type: Active Comparator
description: Patients are presented with symptomatic speech and asymptomatic whisper and, using active EEG-based neurofeedback, are trained to correct their speech by matching their brain patterns to those of whisper. This training is expected to be effective for symptom improvement.
arm group label: Sham neurofeedback BCI
arm group type: Sham Comparator
description: Patients are presented with symptomatic speech and asymptomatic whisper and, using sham EEG-based neurofeedback, are trained to correct their speech by matching their brain patterns to those of whisper. This training is expected not to be effective for symptom improvement.
intervention type: Device
intervention name: neurofeedback brain-computer interface (BCI)
description: The integrated components of BCI system include the high-density EEG, 3D-VR, and a built-in ML platform as a real-time neural signal decoder and neurofeedback controller.
arm group label: Active neurofeedback BCI
arm group label: Sham neurofeedback BCI
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kristina Simonyan, MD, PhD
role: Principal Investigator
affiliation: Massachusetts Eye and Ear
last name: Kristina Simonyan, MD, PhD
phone: 617-573-6016
email: simonyan_lab@meei.harvard.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts Eye and Ear Infirmary
investigator full name: Kristina Simonyan
investigator title: Associate Professor of Otolaryngology - Head and Neck Surgery
mesh term: Dysphonia
mesh term: Dystonia
mesh term: Dystonic Disorders
sharing ipd: No