Voice Tremor in Spasmodic Dysphonia: Central Mechanisms and Treatment Response

NCT01961297 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GCO 09-1156R01DC012545
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Spasmodic Dysphonia; Voice Tremor

Keywords

dystonia; tremor; treatment; sodium oxybate; brain activity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of Voice Breaks

  baseline and Day 1

• Voice Harshness Severity

  baseline and Day 1

• Breathlessness Severity

  baseline and Day 1

• Voice Tremor Severity

  baseline and Day 1

Study Arms (1)

Sodium oxybate

EXPERIMENTAL

Oral administration of a single dose of sodium oxybate (0.75-2.0 gm)

Drug: Sodium oxybate

Interventions

Sodium oxybate DRUG

Sodium oxybate

Also known as: Xyrem

Sodium oxybate

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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;
• 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;
• laryngeal problems, such as vocal fold paralysis, paresis, vocal fold nodules and polyps, carcinoma, chronic laryngitis;
• known past or present history of grade 2 or higher hepatic and renal dysfunction according to the NCI criteria.;
• known past or present history of moderate to severe congestive heart failure;
• 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.

Sponsors & Collaborators

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

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (5)

• 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 RESULT

• O'Flynn LC, Frucht SJ, Simonyan K. Sodium Oxybate in Alcohol-Responsive Essential Tremor of Voice: An Open-Label Phase II Study. Mov Disord. 2023 Oct;38(10):1936-1944. doi: 10.1002/mds.29529. Epub 2023 Jul 14.

  PMID: 37448353 DERIVED

• Simonyan K, Frucht SJ, Blitzer A, Sichani AH, Rumbach AF. A novel therapeutic agent, sodium oxybate, improves dystonic symptoms via reduced network-wide activity. Sci Rep. 2018 Oct 31;8(1):16111. doi: 10.1038/s41598-018-34553-x.

  PMID: 30382161 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Dysphonia; Dystonia; Tremor

Interventions

Sodium Oxybate

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; Dyskinesias

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

A limitation of this study was reliance on patients' self-reports of alcohol response.

Results Point of Contact

• Title: Dr. Kristina Simonyan
• Organization: Icahn School of Medicine at Mount Sinai

kristina.simonyan@mssm.edu

212-241-0656

Study Officials

• Kristina Simonyan, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 9, 2013
• First Posted: October 11, 2013
• Study Start: July 1, 2012
• Primary Completion: June 30, 2017
• Study Completion: June 30, 2017
• Last Updated: November 22, 2017
• Results First Posted: November 22, 2017

Record last verified: 2017-10

Locations

US (1)