Clinical trial NCT02107261
Conditions: Dystonia
Keywords: Musician's Dystonia
Sponsor: Icahn School of Medicine at Mount Sinai
Start date: 2014-03-01; Completion date: 2020-01-27
Enrollment: 21 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

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.

Detailed description:

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: incobotulinumtoxin A intervention 2: Placebo
Intervention descriptions: intervention 1: 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. intervention 2: matching placebo

Protocol documents:
Prot_SAP_000.pdf: 
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
PI: David Simpson, MD
NCT02107261
Document Date: Oct 22, 2019


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
1 
Revised  9/2/14 
Header: 

Protocol Title
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.
Principal Investigators
David Simpson, M.D. 

Date Revised
October 22, 2019

Study Number
GCO#13-1679/HSM#13-00822
Brief Summary of Research (250-400 words): 
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. 


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
2 
Revised  9/2/14 
1) Objectives:
The research question of this exploratory crossover pilot trial is: compared to 
placebo, does BoNT significantly improve the motor performance and subjective 
disability of patients suffering from focal task specific dystonia of the musician’s 
hand? Focal task-specific dystonia of the musician’s hand is a disorder that 
frequently impairs or ends the careers of highly skilled performing artists.  Dr. 
Frucht has personally evaluated more than 170 of these patients over the last 
decade; clinically and anecdotally, BoNT is often used to treat these musicians, 
but few studies exist that quantify their motor and subjective improvement or the 
prevalence of adverse effects.  This trial will be performed using BoNT versus 
placebo in 20 patients with musician’s hand dystonia, to refine quantitative 
measures of performance using Musical Instrument Digital Interface (MIDI) 
technology and high speed video analysis, demonstrate efficacy and tolerability of 
BoNT injections, and provide power calculations for a future multi-center double 
blind clinical trial.  
2) Background
Musician’s dystonia (MD) is characterized by sustained muscle contractions and the
loss of voluntary muscle control; this leads to incoordination and an inability to
properly play one’s musical instrument. The condition is almost exclusively triggered
by the act of playing music, and is therefore considered to be a type of focal task-
specific dystonia. (1,2,12,13) The dystonia can involve muscles of the hand, limb, or
embouchure.(1,4) MD typically affects highly trained musicians and is often
disabling; it affects up to 1% of professional musicians. (3)
The pathophysiology of musician’s dystonia is not well understood. A commonly accepted 
theory suggests deregulation of normal mechanisms of brain plasticity. Changes in brain 
plasticity have been demonstrated in string players where the sensory-motor cortical 
receptive fields of the fingers enlarge with repetitive tasks.(5) As these new cortical 
projections are created, they not only have the potential to augment fine motor control of 
individual fingers, but may also be susceptible to disorganization which may lead to 
dystonia. (6,7) Genetic predisposition is also thought to be a factor in the development of 
MD. In one study, up to 10% of patients with MD were found to have at least one family


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
3 
Revised  9/2/14 
member with dystonia. (3) This familial relationship was noted to be much higher in another 
study after a thorough history and clinical exam was conducted amongst musicians with 
dystonia as well as their family members. (8) No specific candidate gene has been identified 
to date.  
Risk factors that are thought to be contributory to the development of MD have been 
observed in a German study of 591 patients with MD. These included prolonged 
hours of practice, movements that required a high level of spatial and temporal 
precision as well as a predefined temporo-spatial constraints, chronic pain, anxiety 
and perfectionism. In addition, males appeared to be slightly more affected than 
females. (7) 
Treatment of musician’s dystonia is often challenging as the pathophysiology of the 
condition is not well understood, and there are often high expectations for a curative 
measure by the patient. Available treatment options include both pharmacologic and 
non-pharmacologic treatments. Non-pharmacologic treatment consists of 
rehabilitation techniques that practice tactile discrimination with the hope that 
sensory retraining could alleviate the motor symptoms of MD. Ergonomic changes to 
the musical instrument have also been tried to help alleviate motor symptoms. 
Pharmacologic treatment consists of oral medications such as trihexyphenidyl, 
baclofen, phenytoin and primodone, and injections with botulinum toxin. (9) 
Unfortunately, with the exception of botulinum toxin injections, most treatment 
options have shown suboptimal results. 
BoNT injections have shown mixed results in treating focal dystonia, including focal 
task specific dystonia.(11) The toxin can chemically denervate the overactive muscle 
by blocking the transmission of nerve impulses that innervate the dystonic muscle. 
With EMG/electrical stimulation guidance, the muscles contributing to the movement 
disorder can be targeted with fine precision. More recently ultrasound has been 
employed effectively in muscle targeting. BoNT therapy works best for forearm 
muscles and does not show great effect in treating embouchure’s dystonia or dystonia 
affecting shoulder or proximal arm muscles. (2,9) In one study that treated 84 patients 
with MD  with injections of botulinum toxin, 58% of musicians experienced 
improvement of symptoms and 36% experienced long term benefit in their 
performance ability. (10) 


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
4 
Revised  9/2/14 
Musician’s dystonia is a highly disabling disorder and can be a devastating condition 
to the professional musician. Although there is no cure that is currently available, 
treatment with BoNT can offer great symptomatic relief which may enable the 
musician to continue their ability to perform. 
3) Setting of the Human Research
The research will be conducted at the Faculty Practices of Dr. Simpson and Shin at
Mount Sinai Medical Center located at 1468 Madison Ave, New York, NY 10029.
The Faculty Practice and office of Dr. Frucht is located at The Marlene and Paolo
Fresco Institute for Parkinson’s and Movement Disorders.NYU Langone Medical
center. 240 East 38TH ST, 20th Floor, New York, NY, USA 10016. The offices of
Drs. Simpson and Shin are located on the 2nd Floor of the Annenberg Building in the
Neurophysiology Department, Section 218.
4) Resources Available to Conduct the Human Research
Drs. Frucht and. Simpson are experts in the treatment of focal dystonia. They have
many patients that fit the inclusion criteria of musician’s dystonia. Many of the
patients will be referred from Dr. Frucht’s  practice at NYU Langone Medical Center
due in part to his connections with musicians from the Julliard School and other
music schools, organizations, and support groups. A total enrollment of 20 patients is
anticipated over the course of the study.
The study team meets monthly to discuss the research projects which are enrolling
and the various stages of recruitment and to troubleshoot any issues which arise.
Additionally the study team will be educated about the protocol, the investigational
product, and their trial-related duties and functions, through these study team
meetings.  More frequent meetings will be added should a delay in enrollment occur
or if there are major issues concerning the flow of subjects through the visits of the
study.
Drs. Simpson’s, Shin’s and Frucht’s qualifications are included in this application
which includes their biosketches. Their required research education and conflict of
interest statements are available for review
5) Study Design
a) Recruitment Methods


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
5 
Revised  9/2/14 
Patients will be recruited from the Faculty Practices of Drs. Frucht and Simpson. A 
majority of patient recruitment is anticipated through Dr. Frucht’s practice. 
Furthermore, flyers will be posted throughout Mount Sinai Medical Hospital and 
NYU Hospital to increase the potential of recruitment of musicians diagnosed with 
dystonia and forwarded to musical training institutions, musical organizations and 
advocacy groups for patients with dystonia.  IRB approval will be sought when the 
flyers are designed and the study team deems the need for this approach to increase 
study enrollment.   
b) Inclusion and Exclusion Criteria
Any adult patient is eligible for inclusion, provided they meet the following inclusion and
exclusion criteria:
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 NYU Langone Hospital 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.
c) Patients with a medical condition that precludes them from receiving
BoNT injections. Number of Subjects
This will be a placebo-controlled, double-blind, randomized, cross-over pilot
study to assess the efficacy and tolerability of BoNT injections to treat musician’s
dystonia. The study will enroll a total of 2 patients that will be divided into two
groups:


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
6 
Revised  9/2/14 
1) Group 1: Naïve to BoNT treatment (10 patients).
2) Group 2: Prior treatment with BoNT (10 patients).
The study anticipates screening 26 patients to enroll 21 who are eligible   for   
randomization.   
d) Study Timelines
There will be 7 or 10 visits depending on which week would be your optimal dosing over the 
24-28 week study period.  Patients will be seen at weeks 1, 2, 4, 12, 14, 16, and 24, (see
attached flow sheet – appendix 1). If patient needs booster dosage at week 2 or 4, patient will
be asked to return to have another visit at 4 week after optimal dosing. There will be a total
of 7-10 research visits over a 24-28 week period.   All visits are expected to last
approximately 2-3 hours.   The study started in January 2014 and anticipates ending in June
2020 . During the study, we may split Visits so that the patient can be seen easily by Dr.
Frucht and not create a hardship for the participant. If the study visit is split, it will mean that
Dr. Frucht’s assessment will occur prior to the assessment and treatment at Dr. Simpson’s
location on two consecutive days.
e) Study Endpoints
Primary Outcome Measures: 
The principal outcome measure will be improvement in musical performance, 
measured by self-rated questionnaire, quantitative MIDI analysis and blinded high 
speed video analysis. 
Secondary Outcomes Measures: 
Patient reported outcomes will be measured by questionnaires that address adverse 
events; and modified hospital anxiety depression scale (mHADS), and perceived 
stress scale to capture impact of anxiety, depression and stress.   
Motor strength will be tested using the Medical Research Council (MRC) muscle 
scale and a dynamometer to document any weakness the treatment may produce as 
compared to the baseline visit. 


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
7 
Revised  9/2/14 
f) Procedures Involved in the Human Research
Every patient’s dystonic movement disorder will be videotaped at each time point.
The patient will bring in their instrument if possible; a keyboard will be provided
for pianists. The patient will be encouraged to wear similar clothing/jewelry/nail
polish etc. so each video recording will be identical at each time point.
The study will last a total of 24-28 weeks with the schedule as follows:
Visit 1- (Day 0) - Screening and baseline: 
 Consent Form Process – completed prior to any research procedures 
 Comprehensive Neurologic History and Physical Examination (MRC scales and 
dynamometry) 
 Blood tests 
 Patient’s subjective rating scale of symptoms at baseline, HADS and perceived 
stress (questionnaires)  
 Video of targeted hand(s) by Dr. Frucht at NYU Langone medical center 
 Selection of Muscles to inject –  by Dr. Frucht at NYU Langone medical center. 
 Identification of the muscles and Injection of muscles 
Visit 2 and Visit 3 will contain the following evaluations: 
 Brief neurological exam to evaluate for weakness of the targeted muscles and 
surrounded non-targeted muscles (dynamometry, and MRC )  
 Patient’s subjective rating scale of symptoms, HADS and perceived stress 
(questionnaires)  
 Assess for side effects 
 Video of targeted hand(s) by Dr. Frucht at NYU Langone medical center. 
 Administer booster to patients who feel symptoms have not improved 
Visit 4 


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
8 
Revised  9/2/14 
 
Brief neurological exam to evaluate for weakness of the targeted muscles and surrounded 
non-targeted muscles (dynamometry, MRC) 
 Patient’s subjective rating scale of symptoms, HADS and perceived stress 
(questionnaires) 
 Assessment of side effects 
 Video of targeted hand(s) Injection of muscles by Dr. Frucht at NYU Langone 
medical center. 
Visit 4a or 4b. This is optional visit at Week 6, 8 are depending on optimal dosing at 
weeks 2 and 4.  
This visit will assess the improvement in musical performance. It will be 4 weeks after 
optimal booster injection.  
 Brief neurological exam to evaluate for weakness of the targeted muscles and 
surrounded non-targeted muscles (dynamometry, and MRC )  
 Patient’s subjective rating scale of symptoms and perceived stress (questionnaires) 
 Assess for side effects 
 Video of targeted hand(s) by Dr. Frucht at NYU Langone medical center. 
Visit 5; Week 12 (week 14 or 16 depending on previous dosing schedule) will contain the 
following evaluations: 
 Brief neurological exam to evaluate for weakness of the targeted muscles and 
surrounded non-targeted muscles (dynamometry, and MRC )  
 Patient’s subjective rating scale of symptoms, HADS and perceived stress 
(questionnaires)  
 Assess for side effects 
 Video of targeted hand(s) (Groups 1 & 2 will be crossed over and will receive their 
2nd injection cycle) by Dr. Frucht at NYU Langone medical center. 
 Treatment may be deferred for up to 2-4 weeks in any individuals who have 
persistent weakness from the first treatment cycle 


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
9 
Revised  9/2/14 
Visit 6 and visit 7; Week 14 or 16 or 18 depending on previous dosing schedule will contain the 
following evaluations: 
 Brief neurological exam to evaluate for weakness of the targeted muscles and 
surrounded non-targeted muscles (dynamometry, and MRC )  
 Patient’s subjective rating scale of symptoms, HADS and perceived stress 
(questionnaires)  
 Assess for side effects 
 Video of targeted hand(s) by Dr. Frucht at NYU Langone medical center 
 Administer booster to patients who feel symptoms have not improved 
Visit 7a or 7b is optional visit which will be 4 week after optimal dosing injection. 
 Brief neurological exam to evaluate for weakness of the targeted muscles and 
surrounded non-targeted muscles (dynamometry, and MRC )  
 Patient’s subjective rating scale of symptoms, HADS and perceived stress 
(questionnaires)  
 Assess for side effects 
 Video of targeted hand(s) by Dr. Frucht at NYU Langone medical center 
Visit 8 Final follow-up evaluation, this visit will be 12 weeks after optimal dosing 
injection which will be week 24 or 26 or 28 
 Brief neurological exam to evaluate for weakness of the targeted muscles and 
surrounded non-targeted muscles (dynamometry, and MRC )  
 Blood Tests 
 Patient’s subjective rating scale of symptoms, HADS and perceived stress 
(questionnaires) 
 Final assessment for side effects 
 Video tape targeted hand(s). This will occur at Dr. Frucht’s office at NYU 
Langone Medical Center. Participants will be referred for clinical care.  
Rating at the completion of the study: 


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
10 
Revised  9/2/14 
1. Patient rater (self): Will provide a subjective self-assessment score of symptom
improvement in questionnaire form at every visit. They will also be asked to rate
their recorded video performances that will be presented to them in a random
order.
2. Musician rater: A professional musician (of similar genre) will review the
recorded performances in random order and will be asked to rate performance and
presence of dystonia.
3. Neurologist rater: Will review the recorded performances in random order and
asked to rate dystonia and performance.
Participants will be asked to abstain from getting pregnant during the study treatment 
period.  Women who are of child bearing potential will have a pregnancy test prior to 
each visit which has an injection.  Participants (men and women) will be asked to 
maintain birth control throughout the study period and their choice of birth control will 
be notated in the source documents.   
Should a subject become pregnant during the study treatment period, study treatments 
will be discontinued and the pregnancy will be reported as an unexpected AE to the IRB. 
Pregnancies and their follow-up will be monitored  by the study team and reported to the 
sponsor and the IRB. The pregnancy follow-up will include the outcome of the 
pregnancy.  
g) Specimen Banking
Blood specimens are being banked for the possible future analysis of antibody
development. This will be done should there be an adverse event or lack of
response to treatment during the study or to provide safety data for publication
h) Data Management and Confidentiality
Source documents will be created during each study visit for each participant and stored in a 
locked cabinet in Dr. Simpson’s research locked office on Annenberg 2nd Floor.  Only study 
staff will have access to these paper records, and only as required to perform their roles.  The 
participant demographics form and the informed consent document, which contain 


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
11 
Revised  9/2/14 
identifying data will be kept separately from the other documents.  All other documents will 
be identified by the participant’s study identification (ID) number only.  De-identified data 
will be entered into a password protected database that is housed on a secure, encrypted, 
Mount Sinai network drive.  Every attempt will be made to videotape the study visits without 
showing a participant’s face nor will names be used.  The videos will be identified with the 
study subject number and stored in the locked cabinet and locked office in Dr. Frucht’s 
research area.  The de-identified videos will be downloaded on the password protected 
database that is on the secure, encrypted NYU Langone network drive.  Only the study team 
will  have access to these videos.  At the time of the analysis, a blinded neurologist and a 
blinded musician will be shown these tapes, on the  encrypted network within the locked 
office of the study team. Data will be shared through an approved platform called 
www.box.com  provided by the Sinai IT division for the purpose of sharing the data from this 
study. The videotapes will be kept indefinitely for scientific presentations and educational 
forums.   
The statistical analysis will be performed by the investigators with the help of a 
biostatistician at Mount Sinai research institute, Dr. Emilia Bagiella.  A total of 20 
subjects will be enrolled to this two-treatment (BoNT vs. placebo) crossover study.  
The probability is 80% that the study will detect a treatment difference at a two-sided 
0.05 significance level, if the true difference between the treatments is 0.935 units.  
This is based upon the assumption that the within-patient standard of the response 
variable is 1.  Although the signal to noise ratio is not optimal due to the small subject 
size, we believe that this study will be able to detect a significant difference between 
the study drug and placebo.  This is based on reviews of video of robust improvement 
in treated patients.  Keeping the sample size small also allows us to finish recruitment 
within two years, and to complete all phases of the study by 24 months in order to 
supple information for planning for a larger definitive study.  We hope that the 
dropout rate will be less than 3%.   
i) Provisions to Monitor the Data to Ensure the Safety of subjects
Drs. Frucht  and Simpson  will be responsible for monitoring the data to ensure
the safety of all of the participants in the study
MSSM Co-Principal Monitor:
Last Name: Frucht 
First Name: Steven  
Academic Title: Professor 
Phone: 212-263-4838 


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
12 
Revised  9/2/14 
Department: Neurology 
Fax: 646-501-9273 
Mailing Address: 240 East 38TH ST, 20th Floor, 
E-Mail:Steven.Frucht@nyumc.org
New York, NY, USA 10016 
MSSM Co-Principal Monitor: 
Last Name: Simpson  
 First Name:  David  
Academic Title: Professor  
 Phone:  212-241-8748
Department: Neurology 
 Fax: 212-987-3301  
Mailing Address: 1468 Madison Avenue, Box 1052 
New York, NY 10029 
E-mail:  david.simpson@mssm.edu
Drs. Frucht and Simpson have extensive experience in the area of movement disorders.  
Dr. Simpson is an expert in the use of toxin’s in the treatment of dystonia and Dr. Frucht 
in highly knowledgeable about the musicians who have been diagnosed with dystonia as 
it relates to playing his or her musical instrument. Their extensive knowledge will ensure 
patient safety throughout the study.   
1) Adverse events (AE) will be monitored for safety.  At each visit subjects will be
asked non-leading questions such as “do you feel different in any way since the last
visit?”  All observed or volunteered AE’s will be documented in the AE log.
2) Accumulated safety and data information will be reviewed by the monitors (Simpson
and Frucht) during study team meetings.
3) The study does not require any stopping rules for interrupting the study or altering the
study design. The treatments used for the study are lower doses than standard of care.
4) 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.  The selection sheet will be provided to the unblinded co-investigator to
preparing the syringes either with placebo or study drug.
5) AEs will be classified as mild, moderate or severe based upon the following
criteria:  Mild = symptoms do not alter the subject’s normal functioning,
Moderate= symptoms produced some degree of impairment to function but
are not dangerous, uncomfortable or embarrassing to the subject, Severe =


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
13 
Revised  9/2/14 
symptoms are dangerous to the subject’s well-being and causes significant 
impairment of function or incapacitation. 
The relationship of the AE to the treatment will be classified as follows:  
Related:  there is good reason(s) and sufficient evidence to assume that there 
is a causal relationship with the treatment and the AE.  Not related:  there is 
good reason(s) and sufficient evidence to exclude a causal relationship with 
the treatment.  
All AEs will require the investigator to obtain adequate information to 
determine the outcome of the AE and to assess whether it meets criteria as a 
serious adverse event (SAE), which requires immediate notification to the 
funding agency and ethics review board.  The investigator will obtain 
sufficient information to determine the causality of the AE (i.e. treatment or 
other cause); and provide their opinion on causal association (i.e., whether 
they consider the AE related or not related to the study intervention).  Subjects 
will receive follow up until the AE either resolves completely or stabilizes to a 
level acceptable to the investigator.  
All SAEs will be reported within 24 hours of the investigator’s knowledge of 
the event to the ethics review board and/or funding agency.  An SAE is any 
AE during the time period of the study that:  1) results in death, 2) is life 
threatening and places the subject  at immediate risk of death, 3) results in in-
patient hospitalization, 4) results in significant disability/incapacity, where the 
disability is a substantial disruption of a person’s ability to conduct normal 
daily life functions, 5) is an important medical event that may not result in 
death, be life threatening, or require inpatient hospitalization, but which based 
upon the appropriate medical judgment may require medical and/or surgical 
intervention to prevent one of the outcomes listed above. 
6) All data will be reviewed by Drs. Simpson and Frucht for completeness and
accuracy
Should a temporary or permanent suspension of the study occur, in addition to the 
PPHS, we would need to inform the funding agency.  The study has received an  
IND exemption from the FDA. 
j) Withdrawal of Subjects


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
14 
Revised  9/2/14 
Participants may withdraw from the study at any time, with an early withdrawal 
follow up visit to examine and ensure patient safety. Withdrawal or 
discontinuation due to an AE should be distinguished from 
withdrawal/discontinuation due to an insufficient response to the study 
drug/treatment.    
6) Risks to Subjects
Risks from BoNT injections: 
a)
Potential risks of BoNT includes over relaxation of the targeted muscles. Furthermore,
non-targeted muscles may be affected. Participants may experience pain and discomfort
while receiving the injections.
b) Risks for people with breathing or swallowing problems:
Treatment of BoNT to subjects with breathing or swallowing problems may pose
some degree of risk, although this is quite small, particularly with the very low
doses of BoNT (100 units or less) employed in this study of focal musician’s
dystonia. Muscles in the neck that help in breathing and swallowing may be over
relaxed. Subjects may experience severe breathing problems, and inability to
swallow. Food and water may also enter the lungs.
c) Risks from blood sampling
d) The risk of the loss of privacy.
e) There is always the possibility for unknown risks to occur
7) Provisions for Research Related Injury
Medical care will be available to participants in the occurrence of any adverse events.
The participant and his/her insurance company will be responsible for the medical
costs.
8) Potential Benefits to Subjects
While there are no direct benefits to the participants, injections of BoNT may
weaken  over-active muscles and improve the function of the hand(s). Participants
may then be able to play their desired instruments, possibly at the professional level.


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
15 
Revised  9/2/14 
Examination of the effects of BoNT will broaden the knowledge in the treatment of 
musician’s dystonia and other neurological illnesses for the scientific community.  
9) Provisions to Protect the Privacy Interests of Subjects
All Study visits will occur in private exam rooms.  Phone calls and any information
concerning the participant’s involvement in the study will be conducted with the
sensitivity of maintaining the participants privacy.
10)
Economic Impact on Subjects
Participants of the study will not be responsible for any costs. 
11)
Payment to Subjects
Participants will receive a payment of $75 for each visit including reimbursement for 
transportation from NYU Langone medical center to Mount Sinai Hospital by check which 
may take up to 4-6 weeks for processing.  
12)
Consent Process
The study team will use the SOP-090 for conducting the consent form process for
all potential study participants; said consent will apply for all subject visits. Prior
to any study activities, participants will be provided a copy of the consent form,
and undergo a consent process, be screened, and will discuss  the details of the
study. The exam rooms are located at the private practices of Dr. Simpson at
Mount Sinai Medical Center, located at 1468 Madison Ave, New York, NY
10029. The office of Dr. Frucht is located at The Marlene and Paolo Fresco
Institute for Parkinson’s and Movement Disorders. NYU Langone Medical
Center, 240 East 38th St., 20th Floor, New York, NY, 10016.
The offices of Drs. Shin and. Simpson are located on the 2nd Floor of the
Annenberg Building in the Neurophysiology Department, Section 218.
The study will not enroll cognitively impaired adults.   The study team will provide a
non-English language consent form for approval should a patient be eligible for the study
that does not speak English to the IRB prior to enrolling the subject.  A translator will
also be present during the consent form process for non-English speaking subjects.   The


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
16 
Revised  9/2/14 
study team is committed to including patients who are musicians suffering from task-
specific dystonia of the hand.   
13)
Process to Document Consent in Writing
The study will use the SOP-091 and the consent will be documented in writing
using the standard PPHS consent template.
14)
Vulnerable Populations
Include 
Exclude 
Vulnerable Population Type 
x 
Adults unable to consent 
x 
Individuals who are not yet adults (e.g. infants, children, 
teenagers) 
x 
Wards of the State (e.g. foster children) 
x 
Pregnant women 
x 
Prisoners 
15)
Multi-Site Human Research (Coordinating Center)
N/A
16)
Community-Based Participatory Research
N/A
17)
Sharing of Results with Subjects
Subjects will be offered generalized information about the study after the completion of
the data analysis.  Until the study is complete the participants will not be provided their
research information.


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
17 
Revised  9/2/14 
18)
External IRB Review History
N/A
19)
Control of Drugs, Biologics, or Devices
Note: The IDS has its own forms that must be completed and a review process that
must be followed before the IDS representative will sign off on Appendix B for
submission to the PPHS.
All study drug will be maintained by the study unblinded co-investigator in a locked cabinet, 
in a locked room which only the study team has access.  During the treatment visits, the 
blinded investigator will assess the patient and provide  detailed specifications on the 
injection form the muscles to be targeted and the amounts of drug/placebo to be prepared in 
syringes for injection.  The unblinded co-investigator will prepare the study drug/placebo 
according to the detailed information.  A log will be maintained by the study team of the 
study drug vials and the lot  used for each subject.  Upon completion of the study, used and 
unused study drug will be given to Pharmacy for destruction.  
References: 
1. Jankovic J., Ashoori A. Movement Disorders in Musicians. Movement Disorders 2008;
23:1957-1965.
2. Pullman S., Hristova A. Musician’s Dystonia. Neurology 2005;64:186-187.
3. Altenmu¨ller E. Focal dystonia: advances in brain imaging and understanding of fine
motor control in musicians. Hand Clin 2003;19:523–538.
4. Frucht SJ, Fahn S, Greene PE, et al. The natural history of embouchure dystonia. Mov
Disord 2001;16:899–906.
5. Elbert T, Pantev C, Wienbruch C, Rockstroh B, Taub E. Increased cortical representation
of the fingers of the left hand in string players. Science 1995;270(5234):305–307.
6. Munte,T.F., E. Altenm¨uller&L. J¨ancke. 2002. The musician’s brain as a model of
neuroplasticity. Nat. Rev. Neurosci. 3: 473–478.
7. Altenmuller E., Baur V., Hofmann A., et al. Musician’s cramp as manifestation of
maladaptive brain plasticity: arguments from instrumental differences. Annals of the New
York Academy of Sciences 2012; 1252:259-265.
8. Schmidt A, Jabusch HC, Altenmuller E, et al. Dominantly transmitted focal dystonia in
families with musician’s cramp. Neurology 2006;67:691–693.


Protocol Title: 
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 
Principal Investigator 
Name/Contact Info:  
David Simpson, M.D. 
Primary Contact 
Name/Contact Info 
Mary Catherine George 
Mary-catherine.george@mssm.edu  
Date Revised: 
10/22/2019 
Study Number: 
HS: 13-00822   GCO: 13-1679 
18 
Revised  9/2/14 
9. Altenmuller E., Jabusch HC. Focal Dystonia in Musicians: Phenomenology,
Pathophysiology, Triggering Factors, and Treatment. Medical Problems of Performing
Artists 2010; 25: 3-9.
10. Schuele S, Jabusch H-C, Lederman RJ, Altenmüller E. Botulinum toxin injections in the
treatment of musician’s dystonia. Neurology 2004; 64: 341–343.
11. Pullman SL, Greene P, Fahn S, Pedersen SF. Approach to the treatment of limb disorders
with botulinum toxin A. Experience with 187 patients. Arch Neurol 1996;53:617–624.
12. Peterson DA, Berque P, et al. Rating scales for musician’s dystonia: The state of the art.
Neurology 2013; 81(6):589-98.
13. Chang FC, Frucht SJ. Motor and Sensory Dysfunction in Musician’s Dystonia. Curr
Neuropharmacol 2013; 11(1):41-7.