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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 : January 4, 2018
Sponsor:
Collaborator:
National Institute on Deafness and Other Communication Disorders (NIDCD)
Information provided by (Responsible Party):
Kristina Simonyan, Massachusetts Eye and Ear Infirmary

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.

Condition or disease Intervention/treatment Phase
Spasmodic Dysphonia Voice Tremor Vocal Fold Nodules Drug: Sodium Oxybate Phase 2 Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 175 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Central Mechanisms and Treatment Response of Sodium Oxybate in Spasmodic Dysphonia and Voice Tremor
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : August 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Club Drugs Tremor

Arm Intervention/treatment
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.
Drug: Sodium Oxybate
Alcohol challenge test and oral administration of a single dose of sodium oxybate and the matching placebo.
Other Names:
  • Placebo
  • Alcohol

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.
Drug: Sodium Oxybate
Alcohol challenge test and oral administration of a single dose of sodium oxybate and the matching placebo.
Other Names:
  • Placebo
  • Alcohol




Primary Outcome Measures :
  1. Symptom improvement following sodium oxybate vs. placebo intake [ Time Frame: 5 years ]
    Perceptual evaluation of voice symptoms before and after drug and placebo intake


Secondary Outcome Measures :
  1. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03292458


Contacts
Contact: Kristina Simonyan, MD, PhD 617-573-6016 Simonyan_Lab@MEEI.HARVARD.EDU
Contact: Samantha Guiry, MA 617-573-6016 Simonyan_Lab@MEEI.HARVARD.EDU

Locations
United States, Massachusetts
Massachusetts Eye and Ear Infirmary Recruiting
Boston, Massachusetts, United States, 02114
Contact: Kristina Simonyan, MD, PhD    617-573-6016    Simonyan_Lab@MEEI.HARVARD.EDU   
Contact: Samantha Guiry    617-573-6016    Simonyan_Lab@MEEI.HARVARD.EDU   
Sponsors and Collaborators
Kristina Simonyan
National Institute on Deafness and Other Communication Disorders (NIDCD)
Investigators
Principal Investigator: Kristina Simonyan, MD, PhD Massachusetts Eye and Ear Infirmary

Additional Information:
Publications:
Responsible Party: Kristina Simonyan, Director of Laryngology Research, Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT03292458     History of Changes
Other Study ID Numbers: 17-070H
R01DC012545 ( U.S. NIH Grant/Contract )
First Posted: September 25, 2017    Key Record Dates
Last Update Posted: January 4, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kristina Simonyan, Massachusetts Eye and Ear Infirmary:
spasmodic dysphonia
laryngeal dystonia
functional MRI
Xyrem

Additional relevant MeSH terms:
Tremor
Dysphonia
Hoarseness
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Voice Disorders
Laryngeal Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Ethanol
Sodium Oxybate
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General
Anesthetics