The most common form of idiopathic dystonia is adult-onset cervical dystonia (CD), a focal form of dystonia affecting the muscles of the neck. CD is often associated with pain and limited range of motion, and frequently leads to reduced quality of life and disability. Effective long-term treatment options are extremely limited. Recurring botulinum neurotoxin (BoNT) injections can ease the symptoms of CD, but they frequently provide only partial relief and can be associated with intolerable side effects. Deep brain stimulation can be used to treat more severe cases of CD, but this neurosurgical procedure is invasive, on average only about 50% effective and may lead to serious adverse effects. Novel treatment approaches for CD are desperately needed to alleviate symptoms and improve the quality of life for the many who suffer from this chronic and disabling neurological disorder.
Idiopathic CD (neck musculature first and most prominently affected)
18-75 years old (participants excluded if their dystonia symptoms began before age 18 as childhood-onset dystonia typically represents a genetic and/or primary generalized form of dystonia)
Onset of dystonia ≥18 years old, no known hyperkinetic movement disorder-related genetic mutation
Dystonia severity more than minimal and not very severe as defined by Toronto Western Spasmodic Torticollis Rating Scale-2 Motor Severity (TWSTRS-2-Severity) score ≥ 5 and ≤ 20.
History of deep brain stimulation
History of uncontrolled or untreated depression in the prior 3 months, suicidality, or history of suicide attempts
History of uncontrolled liver disease or failure
History of tardive dyskinesia or tardive dystonia
Crossover
Valbenazine
DrugTo assess if valbenazine 80mg daily improves motor symptoms in idiopathic CD patients with persistent symptoms despite current treated with botulinum toxin injections.
Placebo
DrugPlacebo
Toronto Western Spasmodic Torticollis Rating Scale-2 (TWSTRS)-severity score change at 12 weeks of treatment
TWSTRS-2-severity score change at 12 weeks of treatment. The isolated TWSTRS-2-Severity score change was chosen as the primary outcome because the TWSTRS-2-Severity had items dropped from the original TWSTRS as they failed to meet criteria for utility in clinimetric testing,11 and because the primary effect of Valbenazine is expected to be on the motor symptoms and less on pain and disability. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-2) uses the following scoring system for severity: 0: Absent, 1: Mild, which is less than one-third of the possible range and can be intermittent or constant 2: Moderate, which is one-third to two-thirds of the possible range and constant, or severe, which is more than two-thirds of the possible range and intermittent, and 3: Severe and constant
Global Dystonia Severity Rating Scale (GDSRS)
Pain in Dystonia Scale (PIDS), The GDS is a Likert type scale with ratings from 0 to 10 (0 is no dystonia, 1 minimal, 5 moderate and 10 severe dystonia). There are no modifying ratings or weighting factors in the GDS. The total score is the sum of the scores for all the body areas. The maximal total score of the GDS is 140.
Hospital Anxiety and Depression Scale (HADS)
It comprises 14 items (7 items each for anxiety and depression), with a score ranging between 0 and 21 for the anxiety and depression subscales. For each subscale the total score is at most 21. A score of ≥11 is considered a clinically significant disorder, whereas a score between 8 and 10 suggests a mild disorder.
Pittsburgh Sleep Quality Index (PSQI)
The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Scores for each question range from 0 to 3, with higher scores indicating more acute sleep disturbances. Developers have suggested a cut- off score of 5 for the global scale as it correctly identified 88.5% of the patient group in their validation study.
Epworth Sleepiness Scale (ESS)
The ESS is a short, self-administered questionnaire designed to measure sleep propensity in a simple, standardized way (only 8 questions on a total scale of 0 to 24).
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