Brain-Computer Interfaces in Laryngeal Dystonia
Primary Purpose
Laryngeal Dystonia
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
neurofeedback brain-computer interface (BCI)
Sponsored by
About this trial
This is an interventional other trial for Laryngeal Dystonia
Eligibility Criteria
Inclusion criteria:
- Patients will have clinically documented isolated adductor laryngeal dystonia (ADLD) without any other forms of dystonia or tremor. ADLD causes involuntary spasms during vocal fold adduction, leading to voice breaks predominantly on vowels and strained, strangles quality of voice, predominantly affecting voice production during the speaking. Only patients with the ADLD form of disorder will be recruited to minimize the impact of heterogeneity of voice symptomatology on the outcome of these phase 1 studies;
- Healthy controls will be healthy individuals with a negative history of any neurological, psychiatric, or laryngeal problems;
- Age from 18 to 80 years;
- Native English speakers. Non-English-speaking subjects will not be recruited because brain activation and neural network organization are different between native and non-native English speakers;
- Right-handedness (based on Edinburgh Handedness Inventory). Left-handed subjects will not be recruited because brain activation and neural network organization are different between right and left-handed individuals;
- Normal cognitive status (based on Montreal Cognitive Assessment).
Exclusion criteria:
- Subjects who are incapable of giving informed consent will be excluded from the study;
- Pregnant or breastfeeding women until the time they are no longer pregnant or breastfeeding will be excluded from the study. All women of childbearing potential will undergo a urine pregnancy test, which must be negative for study participation;
- Subjects with a past or present medical history of (a) neurological problems, such as stroke, movement disorders (except for ADLD in the patient group), brain tumors, ataxias, myopathies, myasthenia gravis, demyelinating diseases; (b) psychiatric problems, such as schizophrenia, bipolar depression, obsessive-compulsive disorder; (c) laryn¬geal problems, such as vocal fold paralysis, paresis, carcinoma;
- Subjects with impaired hearing, vision, and speaking abilities (except for ADLD), as these would most typically have a neurological origin;
- Patients who have dystonia symptoms at rest in order to avoid the potential confound of dystonic spasms occurring during the asymptomatic task production;
- Patients who are not symptomatic due to the treatment with botulinum toxin injections into the affected muscles. The duration of positive effects of botulinum toxin varies from patient to patient but lasts on average for 3-4 months. All patients will be evaluated to ensure that they are fully symptomatic and are at least three months post-injection prior to study participation;
- To avoid the possibility of confounding effects of drugs acting upon the central nervous system, all subjects will be questioned about any prescribed or over-the-counter medications as part of their initial screening. Those who are on medication(s) affecting the central nervous system will be excluded;
- Subjects with implanted deep brain stimulators will be excluded from the study;
- Subjects will be asked whether they have undergone any head and neck surgeries, particularly any brain surgery and laryngeal surgeries, such as thyroplasty, laryngeal denervation, and selective laryngeal adductor denervation-reinnervation. Because both brain and laryngeal surgery may potentially lead to the brain structure and function re-organization, all subjects with a history of brain and/or laryngeal surgery will be excluded from the study.
Sites / Locations
- Massachusetts Eye and Ear InfirmaryRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Active neurofeedback BCI
Sham neurofeedback BCI
Arm 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.
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.
Outcomes
Primary Outcome Measures
Changes in voice symptoms
Change in the number of dystonic voice breaks as the result of active neurofeedback BCI intervention assessed using perceptual voice analysis
Secondary Outcome Measures
Full Information
NCT ID
NCT04421365
First Posted
May 15, 2020
Last Updated
August 10, 2022
Sponsor
Massachusetts Eye and Ear Infirmary
1. Study Identification
Unique Protocol Identification Number
NCT04421365
Brief Title
Brain-Computer Interfaces in Laryngeal Dystonia
Official Title
Adaptive Closed-loop Brain-computer Interface Therapeutic Intervention in Laryngeal Dystonia
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 18, 2022 (Actual)
Primary Completion Date
August 31, 2026 (Anticipated)
Study Completion Date
August 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts Eye and Ear Infirmary
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The researchers will develop and evaluate the use of adaptive closed-loop brain-computer interface therapeutic intervention in laryngeal dystonia.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Laryngeal Dystonia
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active neurofeedback BCI
Arm Type
Active Comparator
Arm 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 Title
Sham neurofeedback BCI
Arm Type
Sham Comparator
Arm 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(s)
neurofeedback brain-computer interface (BCI)
Intervention 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.
Primary Outcome Measure Information:
Title
Changes in voice symptoms
Description
Change in the number of dystonic voice breaks as the result of active neurofeedback BCI intervention assessed using perceptual voice analysis
Time Frame
At the end of day 5 of the intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria:
Patients will have clinically documented isolated adductor laryngeal dystonia (ADLD) without any other forms of dystonia or tremor. ADLD causes involuntary spasms during vocal fold adduction, leading to voice breaks predominantly on vowels and strained, strangles quality of voice, predominantly affecting voice production during the speaking. Only patients with the ADLD form of disorder will be recruited to minimize the impact of heterogeneity of voice symptomatology on the outcome of these phase 1 studies;
Healthy controls will be healthy individuals with a negative history of any neurological, psychiatric, or laryngeal problems;
Age from 18 to 80 years;
Native English speakers. Non-English-speaking subjects will not be recruited because brain activation and neural network organization are different between native and non-native English speakers;
Right-handedness (based on Edinburgh Handedness Inventory). Left-handed subjects will not be recruited because brain activation and neural network organization are different between right and left-handed individuals;
Normal cognitive status (based on Montreal Cognitive Assessment).
Exclusion criteria:
Subjects who are incapable of giving informed consent will be excluded from the study;
Pregnant or breastfeeding women until the time they are no longer pregnant or breastfeeding will be excluded from the study. All women of childbearing potential will undergo a urine pregnancy test, which must be negative for study participation;
Subjects with a past or present medical history of (a) neurological problems, such as stroke, movement disorders (except for ADLD in the patient group), brain tumors, ataxias, myopathies, myasthenia gravis, demyelinating diseases; (b) psychiatric problems, such as schizophrenia, bipolar depression, obsessive-compulsive disorder; (c) laryn¬geal problems, such as vocal fold paralysis, paresis, carcinoma;
Subjects with impaired hearing, vision, and speaking abilities (except for ADLD), as these would most typically have a neurological origin;
Patients who have dystonia symptoms at rest in order to avoid the potential confound of dystonic spasms occurring during the asymptomatic task production;
Patients who are not symptomatic due to the treatment with botulinum toxin injections into the affected muscles. The duration of positive effects of botulinum toxin varies from patient to patient but lasts on average for 3-4 months. All patients will be evaluated to ensure that they are fully symptomatic and are at least three months post-injection prior to study participation;
To avoid the possibility of confounding effects of drugs acting upon the central nervous system, all subjects will be questioned about any prescribed or over-the-counter medications as part of their initial screening. Those who are on medication(s) affecting the central nervous system will be excluded;
Subjects with implanted deep brain stimulators will be excluded from the study;
Subjects will be asked whether they have undergone any head and neck surgeries, particularly any brain surgery and laryngeal surgeries, such as thyroplasty, laryngeal denervation, and selective laryngeal adductor denervation-reinnervation. Because both brain and laryngeal surgery may potentially lead to the brain structure and function re-organization, all subjects with a history of brain and/or laryngeal surgery will be excluded from the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kristina Simonyan, MD, PhD
Phone
617-573-6016
Email
simonyan_lab@meei.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristina Simonyan, MD, PhD
Organizational Affiliation
Massachusetts Eye and Ear
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts Eye and Ear Infirmary
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristina Simonyan, MD, PhD
Phone
617-573-6016
Email
simonyan_lab@meei.harvard.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Brain-Computer Interfaces in Laryngeal Dystonia
We'll reach out to this number within 24 hrs