Spasmodic DysphoniaPhase 2NCT01961297
Voice Tremor in Spasmodic Dysphonia: Central Mechanisms and Treatment Response
A Phase 2 study testing Sodium oxybate in people with Spasmodic Dysphonia and Voice Tremor, run by Kristina Simonyan at 1 site in United States.
Trial summary
The proposed research aims to determine brain abnormalities in patients with spasmodic dysphonia (SD) and voice tremor (VT) as the basis for characterization of central mechanisms underlying symptom improvement following the use of sodium oxybate, a novel oral medication for the treatment of ethanol-responsive… Read more about this study
- Who is it for?
- Ages 21 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Spasmodic Dysphonia, Voice Tremor
- What is being tested?
- Sodium oxybate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to 30 Jun 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Clinically documented diagnosis of SD and/or VT with positive effects of alcohol on their symptoms;
- Age from 21 to 80 years;
- Native English speakers;
- Right-handedness (based on Edinburgh Handedness Inventory).
Who cannot join
- Subjects who are incapable of giving an informed consent;
- Pregnant and breastfeeding women until a time when they are no longer pregnant or breastfeeding will be excluded from the study. All patients of childbearing potential will be required to agree to use a reliable method of contraception prior and during the treatment with sodium oxybate and prior to receiving botulinum toxin. The method of contraception will be documented in the patient's research chart. All women of childbearing potential will undergo a urine pregnancy test, which must be negative for study participation;
- Subjects with past or present medical history of
- any neurological disorders, except for spasmodic dysphonia and voice tremor, will be excluded from the study in order to maintain the homogenous patient population, allow for the evaluation of drug effect on CNS without confounding by the presence of other neurological conditions, and identify SD and VT disorder-specific changes in brain function and structure. Patients who report other past or present neurological problems, such as stroke, movement disorders other than SD and VT, brain tumors, traumatic brain injury with loss of consciousness, ataxias, myopathies, myasthenia gravis, demyelinating diseases, alcoholism, drug dependence will be excluded. As voice tremor is one of the forms of essential tremor, patients with moderate to severe essential tremor affecting other body parts will be excluded from the study. All patients who have dystonic movements in other than larynx body regions will also be excluded from the study;
- psychiatric problems, such as schizophrenia, major and/or bipolar depression, obsessive-compulsive disorder, will be excluded to maintain the homogenous patient population, allow for the evaluation of drug effect on CNS without confounding by the presence of psychiatric conditions and identify disorder-specific changes in brain function and structure;
- laryngeal problems, such as vocal fold paralysis, paresis, vocal fold nodules and polyps, carcinoma, chronic laryngitis;
Show all 13Show fewer
- known past or present history of grade 2 or higher hepatic and renal dysfunction according to the NCI criteria.;
- known past or present history of moderate to severe congestive heart failure;
- known past or present history of cognitive impairment and active suicidal ideations;
- Patients who are not symptomatic due to treatment with botulinum toxin injections into the laryngeal muscles. The duration of positive effects of botulinum toxin vary from patient to patient but lasts on average for 3-4 months. All patients will be evaluated to ensure that they are fully symptomatic prior to the entering the study, except the substudy, which will examine the effects of combined botulinum toxin and sodium oxybate treatments on abnormal brain function in SD and VT patients;
- To avoid the possibility of confounding effects of drugs acting upon the central nervous system, all study participants will be questioned about any prescribed or over-the-counter medications as part of their initial intake screening. Those patients who receive medication(s) affecting the central nervous system (except sodium oxybate) will be excluded from the study.
- The participants 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 history of brain and/or laryngeal surgery will be excluded from the study.
- The subjects who have tattoos, ferromagnetic objects in their bodies (e.g., implanted stimulators, surgical clips, prosthesis, artificial heart valve, etc.) that cannot be removed for the purpose of MRI study participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
The proposed research aims to determine brain abnormalities in patients with spasmodic dysphonia (SD) and voice tremor (VT) as the basis for characterization of central mechanisms underlying symptom improvement following the use of sodium oxybate, a novel oral medication for the treatment of ethanol-responsive dystonia. The proposed research is relevant to public health because the elucidation of disorder-specific mechanistic aspects of brain organization in SD vs. SD/VT is ultimately expected to lead to establishment of enhanced criteria for clinical management of these disorders, including differential diagnosis and treatment. Thus, the proposed research is relevant to the part of NIH's mission that pertains to developing fundamental knowledge that will help to reduce the burdens of human disability.
Read the detailed description
Spasmodic dysphonia (SD) is a chronic debilitating condition, characterized by selective loss of voluntary voice control during speech production due to uncontrolled spasms in the laryngeal muscles. SD becomes even more incapacitating when it is associated with action-induced voice tremor (VT) due to its poor response to gold standard treatment with botulinum toxin. There is, therefore, a critical need to identify new treatment opportunities for SD/VT patients who receive limited, if any, benefits from botulinum toxin injections. The design and use of novel therapeutic approaches for these patients will, however, be largely unattainable if the central mechanisms of SD and VT development remain unknown. Our long-term goal is to determine the pathophysiology of SD and related disorders, such as VT, for the development of new diagnostic and treatment options for these patients. The objective of this application is to identify brain abnormalities in SD and SD/VT patients as the basis for characterization of central mechanisms underlying symptom improvement following the use of sodium oxybate, a novel pharmacological agent for treatment of ethanol-responsive dystonia. Our central hypothesis is that, compared to SD patients, SD/VT patients will have additional brain abnormalities within the sensorimotor brain circuits controlling voice production, which are being modulated to a greater extent with sodium oxybate treatment. We further postulate that clinical efficacy of sodium oxybate treatment will correlate with its central modulatory effects. The rationale for the proposed research is that identification of distinct brain mechanisms underlying SD and SD/VT clinical manifestations would provide the necessary insights into the pathophysiology of these disorders, while understanding the neural correlates of sodium oxybate action would allow establishment of a scientific rationale for the use of a novel treatment in these disorders. Using a comprehensive approach of multi-modal neuroimaging and clinico-behavioral testing, our central hypothesis will be tested by pursuing two specific aims: (1) determine disorder-specific brain abnormalities in SD and SD/VT patients, and (2) characterize the central effects of sodium oxybate treatment in ethanol-responsive SD and SD/VT patients. This research is innovative because it focuses not only on identification of distinct pathophysiological factors contributing to SD and VT development, but also on discovery of mechanisms of central effects of a novel oral medication, sodium oxybate, which holds promise for treatment of refractory symptoms in SD and SD/VT. The proposed research is significant because it will advance our understanding of the pathophysiology of dystonia in general and SD in particular as well as will have direct impact on improvement of clinical management of SD and SD/VT patients.
- Conditions
- Spasmodic Dysphonia, Voice Tremor
- Being tested
- Sodium oxybate
- Keywords
- dystonia, tremor, treatment, sodium oxybate, brain activity
- Medical subject headings
- Dysphonia, Dystonia, Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium oxybateDrug
Also called Xyrem
Sodium oxybate
| Study group | Role | What they receive |
|---|---|---|
| Sodium oxybate | Experimental | Oral administration of a single dose of sodium oxybate (0.75-2.0 gm) Receives: Drug: Sodium oxybate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Reported Positive Effects.
Number of participants who had reported positive effects of at least one alcohol drink on their voice symptoms
Measured: Day 1
Secondary outcomes (4)
Number of Voice Breaks
The number of SD-characteristic voice breaks in each sentence at pre-drug and post-drug assessment
Measured: baseline and Day 1
Voice Harshness Severity
Visual analog scale of severity (0 for none, 100 for most severe/profound)
Measured: baseline and Day 1
Breathlessness Severity
Visual analog scale of severity (0 for none, 100 for most severe/profound)
Measured: baseline and Day 1
Voice Tremor Severity
Visual analog scale of severity (0 for none, 100 for most severe/profound)
Measured: baseline and Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2013 (estimated)
- Study startJul 2012
- Primary completion30 Jun 2017
- Study completion30 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Spasmodic DysphoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kristina Simonyan
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Deafness and Other Communication Disorders (NIDCD)
- Responsible party
- Sponsor-investigator, Kristina Simonyan, Icahn School of Medicine at Mount Sinai
- Investigators
- Kristina Simonyan, MD, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01961297
- Sponsor's protocol ID
- GCO 09-1156
- Other IDs
- R01DC012545
- Status last verified
- Oct 2017
- First submitted
- 9 Oct 2013
- Last updated
- 22 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Simonyan K, Frucht SJ. Long-term Effect of Sodium Oxybate (Xyrem(R)) in Spasmodic Dysphonia with Vocal Tremor. Tremor Other Hyperkinet Mov (N Y). 2013 Dec 9;3:tre-03-206-4731-1. doi: 10.7916/D8CJ8C5S. eCollection 2013.
PubMed 24386608Rumbach AF, Blitzer A, Frucht SJ, Simonyan K. An open-label study of sodium oxybate in Spasmodic dysphonia. Laryngoscope. 2017 Jun;127(6):1402-1407. doi: 10.1002/lary.26381. Epub 2016 Nov 3.
PubMed 27808415O'Flynn LC, Frucht SJ, Simonyan K. Sodium Oxybate in Alcohol-Responsive Essential Tremor of Voice: An Open-Label Phase II Study. Mov Disord. 2023 Oct;38(10):1936-1944. doi: 10.1002/mds.29529. Epub 2023 Jul 14.
PubMed 37448353Simonyan K, Frucht SJ, Blitzer A, Sichani AH, Rumbach AF. A novel therapeutic agent, sodium oxybate, improves dystonic symptoms via reduced network-wide activity. Sci Rep. 2018 Oct 31;8(1):16111. doi: 10.1038/s41598-018-34553-x.
PubMed 30382161Kirke DN, Frucht SJ, Simonyan K. Alcohol responsiveness in laryngeal dystonia: a survey study. J Neurol. 2015 Jun;262(6):1548-56. doi: 10.1007/s00415-015-7751-2. Epub 2015 May 1.
PubMed 25929664
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Voice Tremor in Spasmodic Dysphonia: Central Mechanisms and Treatment Response
- ClinicalTrials.gov ID
- NCT01961297
- Acronym / sponsor ID
- GCO 09-1156
- Conditions
- Spasmodic Dysphonia, Voice Tremor
- Keywords
- dystonia, tremor, treatment, sodium oxybate, brain activity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Kristina SimonyanUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute on Deafness and Other Communication Disorders (NIDCD)
- Study start
- Jul 2012
- Primary completion
- 30 Jun 2017 (actual)
- Study completion
- 30 Jun 2017 (actual)
- First posted
- 11 Oct 2013 (estimated)
- Results
- Posted 22 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed research aims to determine brain abnormalities in patients with spasmodic dysphonia (SD) and voice tremor (VT) as the basis for characterization of central mechanisms underlying symptom improvement following the use of sodium oxybate, a novel oral medication for the treatment of ethanol-responsive dystonia. The proposed research is relevant to public health because the elucidation of disorder-specific mechanistic aspects of brain organization in SD vs. SD/VT is ultimately expected to lead to establishment of enhanced criteria for clinical management of these disorders, including differential diagnosis and treatment. Thus, the proposed research is relevant to the part of NIH's mission that pertains to developing fundamental knowledge that will help to reduce the burdens of human disability.
Detailed description
Spasmodic dysphonia (SD) is a chronic debilitating condition, characterized by selective loss of voluntary voice control during speech production due to uncontrolled spasms in the laryngeal muscles. SD becomes even more incapacitating when it is associated with action-induced voice tremor (VT) due to its poor response to gold standard treatment with botulinum toxin. There is, therefore, a critical need to identify new treatment opportunities for SD/VT patients who receive limited, if any, benefits from botulinum toxin injections. The design and use of novel therapeutic approaches for these patients will, however, be largely unattainable if the central mechanisms of SD and VT development remain unknown. Our long-term goal is to determine the pathophysiology of SD and related disorders, such as VT, for the development of new diagnostic and treatment options for these patients. The objective of this application is to identify brain abnormalities in SD and SD/VT patients as the basis for characterization of central mechanisms underlying symptom improvement following the use of sodium oxybate, a novel pharmacological agent for treatment of ethanol-responsive dystonia. Our central hypothesis is that, compared to SD patients, SD/VT patients will have additional brain abnormalities within the sensorimotor brain circuits controlling voice production, which are being modulated to a greater extent with sodium oxybate treatment. We further postulate that clinical efficacy of sodium oxybate treatment will correlate with its central modulatory effects. The rationale for the proposed research is that identification of distinct brain mechanisms underlying SD and SD/VT clinical manifestations would provide the necessary insights into the pathophysiology of these disorders, while understanding the neural correlates of sodium oxybate action would allow establishment of a scientific rationale for the use of a novel treatment in these disorders. Using a comprehensive approach of multi-modal neuroimaging and clinico-behavioral testing, our central hypothesis will be tested by pursuing two specific aims: (1) determine disorder-specific brain abnormalities in SD and SD/VT patients, and (2) characterize the central effects of sodium oxybate treatment in ethanol-responsive SD and SD/VT patients. This research is innovative because it focuses not only on identification of distinct pathophysiological factors contributing to SD and VT development, but also on discovery of mechanisms of central effects of a novel oral medication, sodium oxybate, which holds promise for treatment of refractory symptoms in SD and SD/VT. The proposed research is significant because it will advance our understanding of the pathophysiology of dystonia in general and SD in particular as well as will have direct impact on improvement of clinical management of SD and SD/VT patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sodium oxybate | Experimental | Drug: Sodium oxybateOral administration of a single dose of sodium oxybate (0.75-2.0 gm) |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Clinically documented diagnosis of SD and/or VT with positive effects of alcohol on their symptoms;
- Age from 21 to 80 years;
- Native English speakers;
- Right-handedness (based on Edinburgh Handedness Inventory).
Key exclusion criteria (13 listed)
- Subjects who are incapable of giving an informed consent;
- Pregnant and breastfeeding women until a time when they are no longer pregnant or breastfeeding will be excluded from the study. All patients of childbearing potential will be required to agree to use a reliable method of contraception prior and during the treatment with sodium oxybate and prior to receiving botulinum toxin. The method of contraception will be documented in the patient's research chart. All women of childbearing potential will undergo a urine pregnancy test, which must be negative for study participation;
- Subjects with past or present medical history of
- Patients who are not symptomatic due to treatment with botulinum toxin injections into the laryngeal muscles. The duration of positive effects of botulinum toxin vary from patient to patient but lasts on average for 3-4 months. All patients will be evaluated to ensure that they are fully symptomatic prior to the entering the study, except the substudy, which will examine the effects of combined botulinum toxin and sodium oxybate treatments on abnormal brain function in SD and VT patients;
- To avoid the possibility of confounding effects of drugs acting upon the central nervous system, all study participants will be questioned about any prescribed or over-the-counter medications as part of their initial intake screening. Those patients who receive medication(s) affecting the central nervous system (except sodium oxybate) will be excluded from the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium oxybateAlso: XyremSodium oxybate | Drug | Sodium oxybate |
Primary outcome
Number of Participants Who Reported Positive Effects.
Time frame: Day 1
Number of participants who had reported positive effects of at least one alcohol drink on their voice symptoms
4 secondary outcomes
Number of Voice Breaks
Time frame: baseline and Day 1
Voice Harshness Severity
Time frame: baseline and Day 1
Breathlessness Severity
Time frame: baseline and Day 1
Voice Tremor Severity
Time frame: baseline and Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 24386608Simonyan K, Frucht SJ. Long-term Effect of Sodium Oxybate (Xyrem(R)) in Spasmodic Dysphonia with Vocal Tremor. Tremor Other Hyperkinet Mov (N Y). 2013 Dec 9;3:tre-03-206-4731-1. doi: 10.7916/D8CJ8C5S. eCollection 2013.
- Results publication: PubMed 27808415Rumbach AF, Blitzer A, Frucht SJ, Simonyan K. An open-label study of sodium oxybate in Spasmodic dysphonia. Laryngoscope. 2017 Jun;127(6):1402-1407. doi: 10.1002/lary.26381. Epub 2016 Nov 3.
- Derived from this study: PubMed 37448353O'Flynn LC, Frucht SJ, Simonyan K. Sodium Oxybate in Alcohol-Responsive Essential Tremor of Voice: An Open-Label Phase II Study. Mov Disord. 2023 Oct;38(10):1936-1944. doi: 10.1002/mds.29529. Epub 2023 Jul 14.
- Derived from this study: PubMed 30382161Simonyan K, Frucht SJ, Blitzer A, Sichani AH, Rumbach AF. A novel therapeutic agent, sodium oxybate, improves dystonic symptoms via reduced network-wide activity. Sci Rep. 2018 Oct 31;8(1):16111. doi: 10.1038/s41598-018-34553-x.
- Derived from this study: PubMed 25929664Kirke DN, Frucht SJ, Simonyan K. Alcohol responsiveness in laryngeal dystonia: a survey study. J Neurol. 2015 Jun;262(6):1548-56. doi: 10.1007/s00415-015-7751-2. Epub 2015 May 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristina Simonyan, MD, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sodium oxybate in people with Spasmodic Dysphonia and Voice Tremor, run by Kristina Simonyan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Reported Positive Effects. (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01961297, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2017.