Voice Tremor in Spasmodic Dysphonia: Central Mechanisms and Treatment Response
Condition: Spasmodic Dysphonia; Voice Tremor
MeSH terms: Dysphonia; Hoarseness; Tremor
Intervention: Sodium oxybate
Intervention description: Sodium oxybate
Intervention MeSH terms: Sodium Oxybate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: dystonia; tremor; treatment; sodium oxybate; brain activity

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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).

        Exclusion Criteria:

          -  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

               1. 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;

               2. 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;

               3. laryngeal problems, such as vocal fold paralysis, paresis, vocal fold nodules and
                  polyps, carcinoma, chronic laryngitis;

               4. known past or present history of grade 2 or higher hepatic and renal dysfunction
                  according to the NCI criteria.;

               5. known past or present history of moderate to severe congestive heart failure;

               6. 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.