Sodium Oxybate in Spasmodic Dysphonia and Voice Tremor

NCT03292458 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2019P001680R01DC012545
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

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.

Conditions

Spasmodic Dysphonia; Voice Tremor

Keywords

spasmodic dysphonia; laryngeal dystonia; functional MRI; Xyrem

Outcome Measures

Primary Outcomes (2)

• Symptom Severity

  A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and after drug vs. placebo intake. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group.

  40 min after drug or placebo administration

• Minimum Treatment Efficacy

  Pre-specified to analysis based only on alcohol responsiveness (EtOH+). A combined clinician-objective and patient-subjective change in visual analog scale score (min-max 0-100, a higher score is the worse outcome) of symptom severity in EtOH+ patients.

  40 min after drug or placebo administration

Secondary Outcomes (4)

• Treatment Efficacy Dependent on LD Clinical Type

  40 min after drug or placebo administration

• Length of Treatment Efficacy

  40 min to 5 hours after drug or placebo administration

• Relationship Between Alcohol-responsiveness of Symptoms and Drug-induced Symptom Improvement

  40 min after drug or placebo administration

• Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics

  40 min after drug or placebo administration

Study Arms (2)

Clinical response to sodium oxybate

EXPERIMENTAL

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

Central markers of clinical response

EXPERIMENTAL

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

Interventions

Sodium Oxybate DRUG

Alcohol challenge test and oral administration of a single dose of sodium oxybate and the matching placebo.

Also known as: Placebo, Alcohol

Central markers of clinical response; Clinical response to sodium oxybate

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Healthy controls will be healthy volunteers with a negative history of laryngeal, neurological, or psychiatric problems (existing neuroimaging data will be used);
• Age from 21 to 80 years.
• Native English speakers.
• Right-handedness (based on Edinburgh Handedness Inventory).

You may not qualify if:

• Subjects who are incapable of giving an informed consent will be excluded from the study.
• 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.
• All patients with a past or present history of the following conditions will be excluded from the study;
• 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.
• 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.
• Any laryngeal problems, such as vocal fold paralysis, paresis, carcinoma, chronic laryngitis, will be excluded from the study.
• 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.
• Patients with a known past or present history of moderate to severe congestive heart failure will be excluded.
• Patients with a known past or present history of cognitive impairment and active suicidal ideations will be excluded.
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Kristina Simonyan: lead
• National Institute on Deafness and Other Communication Disorders (NIDCD): collaborator

Study Sites (1)

Massachusetts Eye and Ear

Boston, Massachusetts, 02114, United States

Location

Related Publications (6)

• 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.

  PMID: 24386608 BACKGROUND

• 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.

  PMID: 27808415 BACKGROUND

• Battistella G, Fuertinger S, Fleysher L, Ozelius LJ, Simonyan K. Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia. Eur J Neurol. 2016 Oct;23(10):1517-27. doi: 10.1111/ene.13067. Epub 2016 Jun 27.

  PMID: 27346568 BACKGROUND

• Kirke DN, Battistella G, Kumar V, Rubien-Thomas E, Choy M, Rumbach A, Simonyan K. Neural correlates of dystonic tremor: a multimodal study of voice tremor in spasmodic dysphonia. Brain Imaging Behav. 2017 Feb;11(1):166-175. doi: 10.1007/s11682-016-9513-x.

  PMID: 26843004 BACKGROUND

• Kirke 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.

  PMID: 25929664 BACKGROUND

• Simonyan K, Ludlow CL. Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study. Cereb Cortex. 2010 Nov;20(11):2749-59. doi: 10.1093/cercor/bhq023. Epub 2010 Mar 1.

  PMID: 20194686 BACKGROUND

Related Links

• NIH grant description

MeSH Terms

Conditions

Dysphonia

Interventions

Sodium Oxybate; Ethanol

Condition Hierarchy (Ancestors)

Voice Disorders; Laryngeal Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxybutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Alcohols

Limitations and Caveats

A single-center trial: However, the patients were recruited across the US, the UK, and Australia, thus expanding the generalizability of the findings. An inclusion of a greater number of Non-Hispanic White females: LD is well-documented to affect the Non-Hispanic White population with a 4:1 female to male prevalence. Thus, the demographics of patients recruited for this trial reflect the clinical demographics of the disorder in general.

Results Point of Contact

• Title: Prof. Kristina Simonyan
• Organization: Massachusetts Eye and Ear

kristina_simonyan@meei.harvard.edu

617-573-6016

Study Officials

• Kristina Simonyan, MD, PhD

  Massachusetts Eye and Ear

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Otolaryngology - Head & Neck Surgery, Director of Laryngology Research

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 25, 2017
• Study Start: January 22, 2018
• Primary Completion: December 29, 2021
• Study Completion: October 11, 2024
• Last Updated: December 30, 2025
• Results First Posted: April 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)