Dystonia
Conditions
Keywords
Musician's Dystonia
Brief summary
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.
Interventions
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.
DRUGPlacebo
matching placebo
Sponsors
Merz North America, Inc.
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blinded High Speed Video Analysis Comparison | baseline and at 24 weeks | 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. |
| Rating of Overall Musical Performance - Blinded Rater 1 | baseline and at 8 weeks | 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. |
| Rating of Overall Musical Performance - Blinded Rater 2 | baseline and week 8 | 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. |
| Quantitative MIDI Analysis Comparison | baseline at 24 weeks | 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. |
| Physician Global Perception of Change - Blinded Rater 1 | at visit 4 (week 8) | 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. |
| Physician Global Perception of Change - Blinded Rater 2 | at visit 4 (week 8) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Medical Research Council (MRC) Scale | baseline and at 8 weeks | 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. |
| Change in Motor Strength Comparison | baseline and at 8 weeks | 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. |
| Change in Perceived Stress Scale (PSS) | baseline and at 8 weeks | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Then Botulinum Toxin 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. | 11 |
| Botulinum Toxin Then Placebo 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. | 10 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Cycle 2: Week 12-15 | Withdrawal by Subject | 0 | 1 |
| Washout: Weakness Back to Baseline | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Botulinum Toxin Then Placebo | Total | Placebo Then Botulinum Toxin |
|---|---|---|---|
| Age, Continuous | 49.66 years | 50.2 years | 52.68 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 19 Participants | 11 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 9 Participants | 19 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 21 |
| other Total, other adverse events | 12 / 20 | 7 / 21 |
| serious Total, serious adverse events | 0 / 20 | 0 / 21 |
Outcome results
Primary
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.
Time frame: baseline and at 24 weeks
Population: data not collected at 24 weeks
Primary
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.
Time frame: at visit 4 (week 8)
Population: Data not collected for one participant. Data results for Week 8 before crossover treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Physician Global Perception of Change - Blinded Rater 1 | Much Improved | 1 Participants |
| Placebo | Physician Global Perception of Change - Blinded Rater 1 | No Change | 3 Participants |
| Placebo | Physician Global Perception of Change - Blinded Rater 1 | Minimally Improved | 3 Participants |
| Placebo | Physician Global Perception of Change - Blinded Rater 1 | Minimally Worse | 3 Participants |
| Placebo | Physician Global Perception of Change - Blinded Rater 1 | Very much improved | 1 Participants |
| Incobotulinum Toxin Injection | Physician Global Perception of Change - Blinded Rater 1 | Minimally Worse | 1 Participants |
| Incobotulinum Toxin Injection | Physician Global Perception of Change - Blinded Rater 1 | Very much improved | 1 Participants |
| Incobotulinum Toxin Injection | Physician Global Perception of Change - Blinded Rater 1 | Much Improved | 4 Participants |
| Incobotulinum Toxin Injection | Physician Global Perception of Change - Blinded Rater 1 | Minimally Improved | 3 Participants |
| Incobotulinum Toxin Injection | Physician Global Perception of Change - Blinded Rater 1 | No Change | 0 Participants |
Primary
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.
Time frame: at visit 4 (week 8)
Population: Data not collected for one participant. Data results for Week 8 before crossover treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Physician Global Perception of Change - Blinded Rater 2 | Much Improved | 1 Participants |
| Placebo | Physician Global Perception of Change - Blinded Rater 2 | No Change | 3 Participants |
| Placebo | Physician Global Perception of Change - Blinded Rater 2 | Minimal Improved | 4 Participants |
| Placebo | Physician Global Perception of Change - Blinded Rater 2 | Minimal Worse | 3 Participants |
| Placebo | Physician Global Perception of Change - Blinded Rater 2 | Very much improved | 0 Participants |
| Incobotulinum Toxin Injection | Physician Global Perception of Change - Blinded Rater 2 | Minimal Worse | 1 Participants |
| Incobotulinum Toxin Injection | Physician Global Perception of Change - Blinded Rater 2 | Very much improved | 0 Participants |
| Incobotulinum Toxin Injection | Physician Global Perception of Change - Blinded Rater 2 | Much Improved | 2 Participants |
| Incobotulinum Toxin Injection | Physician Global Perception of Change - Blinded Rater 2 | Minimal Improved | 5 Participants |
| Incobotulinum Toxin Injection | Physician Global Perception of Change - Blinded Rater 2 | No Change | 1 Participants |
Primary
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.
Time frame: baseline at 24 weeks
Population: data not collected at 24 weeks
Primary
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.
Time frame: baseline and at 8 weeks
Population: Data not collected for one participant. Data results for Week 8 before crossover treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Rating of Overall Musical Performance - Blinded Rater 1 | +1 Minimally improved | 0 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 1 | -1 Minimal worse | 4 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 1 | +2 Much improved | 2 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 1 | -2 Much worse | 0 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 1 | 0 No change | 5 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 1 | -3 Very much worse | 0 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 1 | +3 Very much improved | 0 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 1 | -3 Very much worse | 0 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 1 | +3 Very much improved | 1 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 1 | +2 Much improved | 2 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 1 | +1 Minimally improved | 3 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 1 | 0 No change | 2 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 1 | -1 Minimal worse | 1 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 1 | -2 Much worse | 0 Participants |
Primary
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.
Time frame: baseline and week 8
Population: Data not collected for one participant. Data results for Week 8 before crossover treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Rating of Overall Musical Performance - Blinded Rater 2 | 0 No Change | 5 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 2 | +2 Much Improved | 3 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 2 | +1 Minimally Improved | 0 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 2 | -1 Minimally Worse | 3 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 2 | -2 Much worse | 0 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 2 | -3 Very much worse | 0 Participants |
| Placebo | Rating of Overall Musical Performance - Blinded Rater 2 | +3 Very much improved | 0 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 2 | -2 Much worse | 0 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 2 | +3 Very much improved | 0 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 2 | -1 Minimally Worse | 1 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 2 | +2 Much Improved | 2 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 2 | -3 Very much worse | 0 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 2 | +1 Minimally Improved | 4 Participants |
| Incobotulinum Toxin Injection | Rating of Overall Musical Performance - Blinded Rater 2 | 0 No Change | 2 Participants |
Secondary
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.
Time frame: baseline and at 8 weeks
Population: Data results for Week 8 before crossover treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Medical Research Council (MRC) Scale | Right FDP dig 2 | 0.07 score on a scale | Standard Error 0.0655 |
| Placebo | Change in Medical Research Council (MRC) Scale | R Lumb dig 4 | -0.013 score on a scale | Standard Error 0.0493 |
| Incobotulinum Toxin Injection | Change in Medical Research Council (MRC) Scale | Right FDP dig 2 | -0.087 score on a scale | Standard Error 0.0654 |
| Incobotulinum Toxin Injection | Change in Medical Research Council (MRC) Scale | R Lumb dig 4 | -0.1190 score on a scale | Standard Error 0.0492 |
Secondary
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.
Time frame: baseline and at 8 weeks
Population: Data results for Week 8 before crossover treatment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Motor Strength Comparison | DYN pnch 3 max | 0.5570 lbs of force exert | Standard Error 0.7079 |
| Placebo | Change in Motor Strength Comparison | Grip max | 3.084 lbs of force exert | Standard Error 4.6889 |
| Placebo | Change in Motor Strength Comparison | DYN pnch 4 avg | 1.065 lbs of force exert | Standard Error 0.5688 |
| Placebo | Change in Motor Strength Comparison | Grip avg | 4.944 lbs of force exert | Standard Error 4.721 |
| Placebo | Change in Motor Strength Comparison | DYN pnch 3 Avg | 1.1440 lbs of force exert | Standard Error 0.6354 |
| Placebo | Change in Motor Strength Comparison | FF D2-3 | 19.526 lbs of force exert | Standard Error 7.1284 |
| Placebo | Change in Motor Strength Comparison | DYN pnch 4 max | 0.679 lbs of force exert | Standard Error 0.5954 |
| Incobotulinum Toxin Injection | Change in Motor Strength Comparison | FF D2-3 | -4.423 lbs of force exert | Standard Error 6.5695 |
| Incobotulinum Toxin Injection | Change in Motor Strength Comparison | DYN pnch 4 max | -3.037 lbs of force exert | Standard Error 0.629 |
| Incobotulinum Toxin Injection | Change in Motor Strength Comparison | DYN pnch 4 avg | -2.323 lbs of force exert | Standard Error 0.5951 |
| Incobotulinum Toxin Injection | Change in Motor Strength Comparison | DYN pnch 3 max | -2.905 lbs of force exert | Standard Error 0.7522 |
| Incobotulinum Toxin Injection | Change in Motor Strength Comparison | DYN pnch 3 Avg | -2.2 lbs of force exert | Standard Error 0.6762 |
| Incobotulinum Toxin Injection | Change in Motor Strength Comparison | Grip max | -25.04 lbs of force exert | Standard Error 4.9933 |
| Incobotulinum Toxin Injection | Change in Motor Strength Comparison | Grip avg | -22.172 lbs of force exert | Standard Error 4.9974 |
Secondary
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
Time frame: baseline and at 8 weeks
Population: Data results for Week 8 before crossover treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Perceived Stress Scale (PSS) | -1.429 score on a scale | Standard Error 0.864 |
| Incobotulinum Toxin Injection | Change in Perceived Stress Scale (PSS) | -0.5031 score on a scale | Standard Error 0.946 |