Sodium Oxybate in Spasmodic Dysphonia and Voice Tremor

October 24, 2023 updated by: Kristina Simonyan

Central Mechanisms and Treatment Response of Sodium Oxybate in Spasmodic Dysphonia and Voice Tremor

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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

Enrollment (Estimated)

140

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts Eye and Ear

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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. Healthy controls will be healthy volunteers with a negative history of laryngeal, neurological, or psychiatric problems (existing neuroimaging data will be used);
  3. Age from 21 to 80 years.
  4. Native English speakers.
  5. 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. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Symptom improvement following sodium oxybate vs. placebo intake
Time Frame: 5 years
Perceptual evaluation of voice symptoms before and after drug and placebo intake
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kristina Simonyan

Collaborators

National Institute on Deafness and Other Communication Disorders (NIDCD)

Investigators

  • Principal Investigator: Kristina Simonyan, MD, PhD, Massachusetts Eye and Ear

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2018

Primary Completion (Estimated)

August 31, 2024

Study Completion (Estimated)

August 31, 2024

Study Registration Dates

First Submitted

September 20, 2017

First Submitted That Met QC Criteria

September 20, 2017

First Posted (Actual)

September 25, 2017

Study Record Updates

Last Update Posted (Actual)

October 26, 2023

Last Update Submitted That Met QC Criteria

October 24, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019P001680
  • R01DC012545 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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