Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician's Hand

Study Overview
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Brief Summary
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The investigational drug being studied in this protocol is Incobotulinumtoxin A (Xeomin®). Botulinum toxin (BoNT) prevents the release of the acetylcholine from peripheral nerves, inhibiting muscle contractions. BoNT is effective in relaxing overactive muscles. In musician's dystonia, the ability to reduce abnormally overactive muscles in the hand can be critical for the musical professional to continue his or her career. With the use of EMG/electrical stimulation and/or ultrasound guidance, the injector can precisely localize the individual muscles that are affected in this condition with great accuracy. Prior studies have shown that BoNT injections produce beneficial effects in forearm muscles, and less effect in shoulder or proximal arm muscles. Possible risks in treating patients with BoNT include excessive weakness of the injected muscles. The drug may also affect non-targeted muscles. However these risks will be minimized during the screening period by carefully targeting the affected muscles and by administering low doses of BoNT. Small booster doses may be given at follow up visit (2, 4, 14 and 16-weeks after the primary injection date) if the initial injection was insufficient to produce sufficient efficacy in relief of the focal dystonia and did not produce excess weakness of the targeted muscle.

Official Title
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A Placebo-Controlled, Double-Blind, Randomized, Cross Over Pilot Study Of The Efficacy And Tolerability Of Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician's Hand

Conditions
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Dystonia

Intervention / Treatment
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* Drug: incobotulinumtoxin A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with focal task-specific dystonia of one or both hands, selectively triggered by performance on a musical instrument. Patients must have been evaluated by Dr. Frucht at the Movement Disorders Division of Mount Sinai Medical Center as part of their clinical care. Patients whose performance on an instrument is directly linked to their occupation. Patients must be between the ages of 18 and 80. Impairment in musical performance must be visible and demonstrable. Exclusion Criteria: Patients whose dystonia is not severe enough to interfere with musical performance in the opinion of a skilled examiner. Patients with unstable medical conditions or psychiatric conditions. Patients with a medical condition that precludes them from receiving BoNT injections.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo Then Botulinum Toxin<br>Placebo dose first does then boosters at week 2 and week 4 then 4 weeks washout, then Incobotulinumtoxin A first dose, with boosters at 2 week and week 4. | Drug: incobotulinumtoxin A<br>* Incobotulinumtoxin A is being used on average doses between 10U and 30 Units per subject, but at no time will any subject receive over 100 Units. Each study visit, the assessing physician will select the muscles and the amounts of medication to be injected.<br>* Other names: Xeomin;Drug: Placebo<br>* matching placebo<br>|
| Active Comparator: Incobotulinumtoxin A Then Placebo<br>Incobotulinumtoxin A dose first does then boosters at week 2 and week 4 then 4 weeks washout, then Placebo first dose, with boosters at 2 week and week 4. | Drug: incobotulinumtoxin A<br>* Incobotulinumtoxin A is being used on average doses between 10U and 30 Units per subject, but at no time will any subject receive over 100 Units. Each study visit, the assessing physician will select the muscles and the amounts of medication to be injected.<br>* Other names: Xeomin;Drug: Placebo<br>* matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician Global Perception of Change - Blinded Rater 1 | The principal outcome measure was improvement in musical performance, measured by blinded rater, using physician global perception of change at post treatment compared to at 8 weeks. Categories are very much improved, much improved, minimal improved, no change, and minimal worse. | at visit 4 (week 8) | 
| Physician Global Perception of Change - Blinded Rater 2 | The principal outcome measure was improvement in musical performance, measured by blinded rater, using physician global perception of change at post treatment compared to at 8 weeks. Categories are very much improved, much improved, minimal improved, no change, and minimal worse. | at visit 4 (week 8) | 
| Rating of Overall Musical Performance - Blinded Rater 1 | Rating of overall musical performance based on comparison to baseline video at week 8. Rating from +3, very much improved to -3, very much worse. Higher score indicates more improvement. | baseline and at 8 weeks | 
| Rating of Overall Musical Performance - Blinded Rater 2 | Rating of overall musical performance based on comparison to baseline video at week 8. Best Overall Musical Performance on 7 point scale from +3 Very much improved to -3 Very much worse. Higher score indicates more improvement. | baseline and week 8 | 
| Quantitative MIDI Analysis Comparison | The principal outcome measure will be improvement in musical performance, measured by self-rated questionnaire, quantitative Musical Instrument Digital Interface (MIDI) analysis and blinded high speed video analysis post treatment compared to baseline and 24 weeks. | baseline at 24 weeks | 
| Blinded High Speed Video Analysis Comparison | The principal outcome measure will be improvement in musical performance, measured by self-rated questionnaire, quantitative MIDI analysis and blinded high speed video analysis post treatment compared to baseline and 24 weeks. | baseline and at 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Perceived Stress Scale (PSS) | Patient reported outcomes measured by questionnaires that address adverse events and the impact of quality of life using the perceived stress scale. A 10-item questionnaire, each item scored 0 (never) to 4 (very often), full scale from 0-40, with higher score indicating higher perceived stress. the more often the person perceives stress Change in PSS at week 8 compared to baseline | baseline and at 8 weeks | 
| Change in Medical Research Council (MRC) Scale | Motor strength using a dynamometer of the finger/wrist/elbow flexors to document any treatment induced weakness. Scale from 0-4, higher score indicates poorer health outcomes. | baseline and at 8 weeks | 
| Change in Motor Strength Comparison | Motor strength tested using a dynamometer to document any weakness the treatment may produce as compared to the baseline visit and 8 weeks. Dynamometer (DYN) - is a mechanical device that measures the pounds of force that a muscle exerts, Grip - a device that measures grip strength, and finger flexors digit 2 and 3 (FF d2-3). These measures are the amount of lbs of force exert. The higher number is the highest exerted out of 3 tries. | baseline and at 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Musician's Dystonia