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Sodium Oxybate in Spasmodic Dysphonia and Voice Tremor

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ClinicalTrials.gov Identifier: NCT03292458
Recruitment Status : Recruiting
First Posted : September 25, 2017
Last Update Posted : February 20, 2020
Sponsor:
Collaborator:
National Institute on Deafness and Other Communication Disorders (NIDCD)
Information provided by (Responsible Party):
Kristina Simonyan, Massachusetts Eye and Ear Infirmary

Tracking Information
First Submitted Date  ICMJE September 20, 2017
First Posted Date  ICMJE September 25, 2017
Last Update Posted Date February 20, 2020
Actual Study Start Date  ICMJE September 1, 2017
Estimated Primary Completion Date August 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2017)
Symptom improvement following sodium oxybate vs. placebo intake [ Time Frame: 5 years ]
Perceptual evaluation of voice symptoms before and after drug and placebo intake
Original Primary Outcome Measures  ICMJE
 (submitted: September 20, 2017)
Symptom improvement following sodium oxybate intake vs. placebo [ Time Frame: 5 years ]
Perceptual evaluation of voice symptoms before and after drug and placebo intake
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2017)
Attenuation of brain functional abnormalities following sodium oxybate vs. placebo [ Time Frame: 5 years ]
Statistical examination of brain functional activity before and after drug and placebo intake
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sodium Oxybate in Spasmodic Dysphonia and Voice Tremor
Official Title  ICMJE Central Mechanisms and Treatment Response of Sodium Oxybate in Spasmodic Dysphonia and Voice Tremor
Brief Summary Using a comprehensive approach of clinico-behavioral testing, neuroimaging and pharmacogenetics, the researchers will examine the clinical effects of sodium oxybate and the matched placebo on voice symptoms in spasmodic dysphonia and voice tremor.
Detailed Description Spasmodic dysphonia (SD), or laryngeal dystonia, is a chronic debilitating condition that selectively affects speech production due to involuntary spasms in the laryngeal muscles. SD often extends beyond the impairment of vocal communication causing significant occupational disability and life-long social isolation. SD becomes even more incapacitating when it is associated with dystonic voice tremor (VT), which is present in about 1/3 of SD patients and is characterized by the inability to sustain a vowel for more than a few seconds. Current treatment of these disorders is limited to the temporary management of voice symptoms with repeated injections of botulinum toxin into the laryngeal muscles. These injections, however, are not fully effective in all SD patients and even less so in combined SD and VT cases. There is, therefore, a critical need to identify alternative therapeutic options that specifically target the pathophysiology of these disorders. On the other hand, the design and the use of such novel therapeutic approaches will be largely unattainable if their central mechanisms of action remain unknown. The objective of this study is to elucidate the primary determinants of clinical response to a novel oral medication, sodium oxybate (Xyrem®), in alcohol-responsive SD and VT patients. Using a comprehensive approach of clinico-behavioral testing, neuroimaging and pharmacogenetics, we aim to determine the clinical response of SD and VT symptoms to sodium oxybate and identify the primary markers of its clinical benefits. This study will use a controlled experimental design that focuses on detailed characterization of primary effects of a novel oral medication, sodium oxybate, for treatment of SD and VT symptoms.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE
  • Spasmodic Dysphonia
  • Voice Tremor
  • Vocal Fold Nodules
Intervention  ICMJE Drug: Sodium Oxybate
Alcohol challenge test and oral administration of a single dose of sodium oxybate and the matching placebo.
Other Names:
  • Placebo
  • Alcohol
Study Arms  ICMJE
  • Experimental: Clinical response to sodium oxybate
    In contrast to placebo but similar to alcohol, sodium oxybate is expected to be most effective in reducing voice symptoms in alcohol-responsive SD and VT.
    Intervention: Drug: Sodium Oxybate
  • Experimental: Primary markers of clinical response
    The clinical outcome is expected to be determined by selective modulation of functional abnormalities in the brain regions controlling speech sensorimotor processing and integration in association with underlying gene variants.
    Intervention: Drug: Sodium Oxybate
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 20, 2017)
175
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 31, 2022
Estimated Primary Completion Date August 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients with SD and combined SD and VT will have a clinically documented adductor or abductor form of disorder, either with or without positive effects of alcohol on their voice symptoms;
  2. Patients with vocal fold nodules (VFN) will have clinically documented vocal fold nodules;
  3. Healthy controls will be healthy volunteers with a negative history of laryngeal, neurological, or psychiatric problems (existing neuroimaging data will be used);
  4. Age from 21 to 80 years.
  5. Native English speakers.
  6. Right-handedness (based on Edinburgh Handedness Inventory).

Exclusion Criteria:

  1. Subjects who are incapable of giving an informed consent will be excluded from the study.
  2. 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 to and during the study. 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.
  3. All patients with a past or present history of the following conditions will be excluded from the study;

    1. Except for SD and dystonic VT, any neurological disorders, such as stroke, movement disorders, brain tumors, traumatic brain injury with loss of consciousness, ataxias, myopathies, myasthenia gravis, demyelinating diseases, alcoholism, drug dependence. Patients with tremor affecting other body parts will be excluded from the study. All patients who have dystonic movements in the body regions other than the larynx will be excluded from the study. This will allow maintaining the homogenous patient population and evaluating central drug effects without confounding by the presence of other neurological conditions.
    2. Any psychiatric problems, such as schizophrenia, major and/or bipolar depression, obsessive-compulsive disorder, will be excluded to maintain the homogenous patient population and allow for the evaluation of central drug effect without confounding by the presence of psychiatric conditions.
    3. Except for VFN in the VFN group, any laryngeal problems, such as vocal fold paralysis, paresis, carcinoma, chronic laryngitis, will be excluded from the study.
    4. Patients with a known past or present history of grade 2 or higher hepatic and renal dysfunction according to the NCI criteria will be excluded.
    5. Patients with a known past or present history of moderate to severe congestive heart failure will be excluded.
    6. Patients with a known past or present history of cognitive impairment and active suicidal ideations will be excluded.
  4. Patients who are not symptomatic due to treatment with botulinum toxin injections into the laryngeal muscles will be excluded from the study until the time when they are fully symptomatic. The duration of positive effects of botulinum toxin vary from patient to patient, lasting on average 3-4 months. All patients will be evaluated to ensure that they are fully symptomatic prior to the entering the study.
  5. To avoid the possibility of confounding effects of drugs acting upon the central nervous system, all patients 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 for sodium oxybate) will be excluded from the study.
  6. Patients 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.
  7. Patients who have tattoos, ferromagnetic objects in their bodies (e.g., implanted stimulators, surgical clips, prosthesis, artificial heart valve, etc.) that are not MRI comparable and/or cannot be removed for the purpose of MRI study participation will be excluded from the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kristina Simonyan, MD, PhD 617-573-6016 Simonyan_Lab@MEEI.HARVARD.EDU
Contact: Azadeh Hamzehei Sichani, MA 617-573-6016 Simonyan_Lab@MEEI.HARVARD.EDU
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03292458
Other Study ID Numbers  ICMJE 17-070H
R01DC012545 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kristina Simonyan, Massachusetts Eye and Ear Infirmary
Study Sponsor  ICMJE Kristina Simonyan
Collaborators  ICMJE National Institute on Deafness and Other Communication Disorders (NIDCD)
Investigators  ICMJE
Principal Investigator: Kristina Simonyan, MD, PhD Massachusetts Eye and Ear Infirmary
PRS Account Massachusetts Eye and Ear Infirmary
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP