Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01961297
Other study ID # GCO 09-1156
Secondary ID R01DC012545
Status Completed
Phase Phase 2
First received October 9, 2013
Last updated October 26, 2017
Start date July 2012
Est. completion date June 30, 2017

Study information

Verified date October 2017
Source Icahn School of Medicine at Mount Sinai
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 53
Est. completion date June 30, 2017
Est. primary completion date June 30, 2017
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 21 Years to 80 Years
Eligibility Inclusion Criteria:

- 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).

Exclusion Criteria:

- 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

1. 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;

2. 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;

3. laryngeal problems, such as vocal fold paralysis, paresis, vocal fold nodules and polyps, carcinoma, chronic laryngitis;

4. known past or present history of grade 2 or higher hepatic and renal dysfunction according to the NCI criteria.;

5. known past or present history of moderate to severe congestive heart failure;

6. 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Sodium oxybate
Sodium oxybate

Locations

Country Name City State
United States Icahn School of Medicine at Mount Sinai New York New York

Sponsors (3)

Lead Sponsor Collaborator
Kristina Simonyan National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Rumbach 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. — View Citation

Simonyan K, Frucht SJ. Long-term Effect of Sodium Oxybate (Xyrem®) in Spasmodic Dysphonia with Vocal Tremor. Tremor Other Hyperkinet Mov (N Y). 2013 Dec 9;3. pii: tre-03-206-4731-1. doi: 10.7916/D8CJ8C5S. eCollection 2013. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Day 1
Secondary Number of Voice Breaks The number of SD-characteristic voice breaks in each sentence at pre-drug and post-drug assessment baseline and Day 1
Secondary Voice Harshness Severity Visual analog scale of severity (0 for none, 100 for most severe/profound) baseline and Day 1
Secondary Breathlessness Severity Visual analog scale of severity (0 for none, 100 for most severe/profound) baseline and Day 1
Secondary Voice Tremor Severity Visual analog scale of severity (0 for none, 100 for most severe/profound) baseline and Day 1
See also
  Status Clinical Trial Phase
Recruiting NCT06111027 - Usability of Vibro-tactile Stimulation to Treat Spasmodic Dysphonia Phase 1/Phase 2
Withdrawn NCT02061943 - Examining the Spasmodic Dysphonia Diagnosis and Assessment Procedure (SD-DAP) for Measuring Symptom Change N/A
Recruiting NCT05158166 - DaxibotulinumtoxinA Injection for Treatment of Adductor Spasmodic Dysphonia Phase 1/Phase 2
Recruiting NCT05580302 - Cortical Silent Period in Laryngeal Dystonia
Recruiting NCT05150106 - Characterization of Clinical Phenotypes of Laryngeal Dystonia and Voice Tremor
Recruiting NCT05216770 - Understanding Disorder-specific Neural Pathophysiology in Laryngeal Dystonia and Voice Tremor Early Phase 1
Recruiting NCT05150093 - Deep Brain Stimulation in Laryngeal Dystonia and Voice Tremor N/A
Completed NCT00713414 - Role of Neurotransmission and Functional CNS Networks in Spasmodic Dysphonia
Completed NCT00118586 - Neuropathology of Spasmodic Dysphonia
Not yet recruiting NCT04938154 - A Phase 2 Trial of Deep Brain Stimulation for Spasmodic Dysphonia Phase 2
Active, not recruiting NCT03292458 - Sodium Oxybate in Spasmodic Dysphonia and Voice Tremor Phase 2/Phase 3
Completed NCT02957942 - rTMS in Spasmodic Dysphonia N/A
Completed NCT02558634 - Thalamic Deep Brain Stimulation for Spasmodic Dysphonia- DEBUSSY Trial N/A
Terminated NCT00895063 - Effect of Vocal Exercise After Botulinum Toxin Injection for Spasmodic Dysphonia N/A
Completed NCT05158179 - Assessment of Laryngopharyngeal Sensation in Adductor Spasmodic Dysphonia N/A
Enrolling by invitation NCT05892770 - Zinc Supplementation Prior to Botox Injections for Spasmodic Dysphonia Phase 1/Phase 2
Completed NCT04648891 - Spasmodic Dysphonia Pain Phase 2/Phase 3
Completed NCT03042962 - Brain Networks in Dystonia
Not yet recruiting NCT06078527 - Assessment of Laryngopharyngeal Sensation: Cancer Survivor Cohort N/A
Completed NCT03746509 - Laryngeal Vibration for Spasmodic Dysphonia N/A