Voice Tremor in Spasmodic Dysphonia: Central Mechanisms and Treatment Response
Condition: Spasmodic Dysphonia; Voice Tremor
MeSH terms: Dysphonia; Hoarseness; Tremor
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Spasmodic dysphonia (SD) is a chronic debilitating condition, characterized by selective loss
      of voluntary voice control during speech production due to uncontrolled spasms in the
      laryngeal muscles. SD becomes even more incapacitating when it is associated with
      action-induced voice tremor (VT) due to its poor response to gold standard treatment with
      botulinum toxin. There is, therefore, a critical need to identify new treatment opportunities
      for SD/VT patients who receive limited, if any, benefits from botulinum toxin injections. The
      design and use of novel therapeutic approaches for these patients will, however, be largely
      unattainable if the central mechanisms of SD and VT development remain unknown. Our long-term
      goal is to determine the pathophysiology of SD and related disorders, such as VT, for the
      development of new diagnostic and treatment options for these patients. The objective of this
      application is to identify brain abnormalities in SD and SD/VT patients as the basis for
      characterization of central mechanisms underlying symptom improvement following the use of
      sodium oxybate, a novel pharmacological agent for treatment of ethanol-responsive dystonia.
      Our central hypothesis is that, compared to SD patients, SD/VT patients will have additional
      brain abnormalities within the sensorimotor brain circuits controlling voice production,
      which are being modulated to a greater extent with sodium oxybate treatment. We further
      postulate that clinical efficacy of sodium oxybate treatment will correlate with its central
      modulatory effects. The rationale for the proposed research is that identification of
      distinct brain mechanisms underlying SD and SD/VT clinical manifestations would provide the
      necessary insights into the pathophysiology of these disorders, while understanding the
      neural correlates of sodium oxybate action would allow establishment of a scientific
      rationale for the use of a novel treatment in these disorders. Using a comprehensive approach
      of multi-modal neuroimaging and clinico-behavioral testing, our central hypothesis will be
      tested by pursuing two specific aims: (1) determine disorder-specific brain abnormalities in
      SD and SD/VT patients, and (2) characterize the central effects of sodium oxybate treatment
      in ethanol-responsive SD and SD/VT patients. This research is innovative because it focuses
      not only on identification of distinct pathophysiological factors contributing to SD and VT
      development, but also on discovery of mechanisms of central effects of a novel oral
      medication, sodium oxybate, which holds promise for treatment of refractory symptoms in SD
      and SD/VT. The proposed research is significant because it will advance our understanding of
      the pathophysiology of dystonia in general and SD in particular as well as will have direct
      impact on improvement of clinical management of SD and SD/VT patients.
    

Intervention name(s): Sodium oxybate
Intervention type(s): Drug
Intervention description(s): Sodium oxybate
Other intervention name(s): Xyrem
Intervention MeSH terms: Sodium Oxybate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: dystonia; tremor; treatment; sodium oxybate; brain activity