Clinical trial NCT01921270
Conditions: Oral Dystonia Tardive Dystonia
Keywords: Oromandibular Dystonia Oral Dystonia Tardive Dystonia botulinum toxin abobotulinumtoxinA
Sponsor: Emory University
Start date: 2013-08-01; Completion date: 2017-02-08
Enrollment: 18 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to study the efficacy and safety of AbobotulinumtoxinA (Dysport) for use in Oromandibular Dystonia (OMD).

Detailed description:
Oromandibular dystonia (OMD) is an uncommon, disabling form of cranial dystonia, involving involuntary movements of the lower facial, masticatory, and lingual muscles. This can cause jaw movements including opening, closure, protrusion, retraction, or deviation. Common additional facial movements involve grimacing or lip pursing. When there is tongue involvement, it usually presents as tongue protrusion or curling. Such patients are impaired in relation to eating, speaking and swallowing

This study aims to evaluate the efficacy and safety of a low dose of Dysport® deemed tolerable during phase 1 in subjects with oromandibular dystonia (OMD).

Participants will be injected with Dysport® only, with an unblinded open-label disclosure. The safety and efficacy pf receiving Dysport® will be recorded for all subjects that undergo injection. All subjects will be examined and videotaped at the injection visit, then at 6 and 12 weeks after injection with a standardized protocol. The primary outcome will be blinded examination scores of the videos performed after the study is complete.The evaluators will be three different movement disorders experts, not otherwise involved in the study, who will review the videotaped examinations, presented in a random order, using the Global Dystonia Rating scale (GDS). Evaluators will rate the dystonia at baseline (injection visit) and 6 weeks after injection.

Arms: arm 1: Participants with OMD who have been previously treated with any botulinum toxin Type A will be injected with Dysport®.
Interventions: intervention 1: Low Dose - AbobotulinumtoxinA
Intervention descriptions: intervention 1: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom.

Muscles that may be included for in injection for OMD with Jaw Closing:

Medial Pterygoid 50 units, Masseter 25 units

Muscles that may be included in injection for OMD with Jaw Opening:

Lateral Pterygoid 50 units, Anterior digastrics 10 units

Muscle that will be included in injection for OMD with Tongue Protrusion:

Genioglossus 7.5 units

Protocol documents:
Prot_SAP_000.pdf: 
A Pilot Dose Ranging Study of Dysport® (AbobotulinumtoxinA) in the Treatment of 
Oromandibular Dystonia 
 3 March 2015 
NCT01921270 
 
 


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Enter ESS Title : A Pilot Dose Ranging Study of Dysport® (AbobotulinumtoxinA) in the 
treatment of Oromandibular Dystonia 
EXTERNAL SPONSOR 
NAME, LOCATION : 
PI: Stewart Factor, DO 
Professor and Director, Movement Disorders Program 
Emory University 
12 Executive Park Drive 
Atlanta, GA 30329 
E-mail: sfactor@emory.edu 
Tel: 404.712-7262 
STUDY TITLE : 
A Pilot Dose Ranging Study of Dysport® 
(AbobotulinumtoxinA) in the treatment of Oromandibular 
Dystonia 
STUDY DESIGN : 
Study Rationale: 
Oromandibular dystonia (OMD) is an uncommon, disabling 
form of cranial dystonia, involving involuntary movements 
of the lower facial, masticatory, and  lingual muscles.  This 
can cause jaw movements including opening, closure, 
protrusion, retraction, or deviation. Common additional 
facial movements involve grimacing or lip pursing. When 
there is tongue involvement, it usually presents as tongue 
protrusion or curling [1, 2].  Such patients are impaired in 
relation to eating, speaking and swallowing. Most cases are 
idiopathic, followed by drug induced (tardive dystonia) [3]. 
OMD comprises 3.1% of all focal dystonias [4]  and its 
prevalence has been estimated in several studies to be 0.3 
per 100,000 [5], 68.9 per million in the US [6] , 2.8 per 
100,00 in Iceland [7] , and 0.8 per 100,000 in an Oslo, 
Norway based study[8]. When included as part of a 
segmental dystonia, which includes “cranial dystonia,” 
“Brueghel’s Syndrome,” or “Meige’s Syndrome,” the 
prevalence is increased. 
Botulinum toxin injection is considered the treatment of 
choice for most patients with focal dystonia, including 
OMD.  Oral medications can also be used, including 
benzodiazepines (e.g., clonazepam, diazepam), 
anticholinergics (e.g., trihexyphenidyl, benztropine), and 
GABAergic drugs (e.g., baclofen, tizanidine).  However, 
the impact of these medications is generally disappointing. 
For those patients with a tardive dystonia, tetrabenazine can 
be used [9]. 


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Study Design: 
Interventional , single site, prospective study with 2 parts: 
1/ Dose raging (aim 1): 3 OMD groups undergoing 3 
different Dysport® dosages with a step wise approach 
based on safety response. 6 weeks duration for the 3 
groups. 
2/ Efficacy & safety assessment of Dysport® selected dose 
from study part 1 (aim 2): 1 single arm with OMD subjects. 
12 weeks duration. 
 
Study Specific Aims: 
 
Aim 1: To determine the best dose range for Dysport® for 
the treatment of oromandibular dystonia 
 
In order to address Aim 1, patients with OMD who have 
been previously treated with any botulinum toxin Type A 
(abobotulinumtoxinA, onabotulinumtoxinA and 
incobotulinumtoxinA) and responded will be recruited into 
this study.  The muscles to be injected will be tailored to 
the individual’s presentation and up to the injector’s 
discretion, but if a muscle is chosen it will be given a set 
amount of Dysport® (abobotulinumtoxinA )(see table 2). 
The subject will be injected with Dysport® only, with an 
unblinded open-label disclosure.  There will be three dose 
levels and three subjects will be injected in each (OMD 
type for each group: 2 jaw opening + 1jaw closing). 
As there is no standard amount of Dysport® used for the 
treatment of OMD, we have estimated a dose range from 
cases in the literature [10, 11] [12] and discussion with Dr. 
Raymond Rosales of the Philippines who has a substantial 
experience injecting the jaw in Filipino patients with Lubag 
disease.  There was some discrepancy in dosages between a 
review paper by Bhidayasiri [12] and Dr. Rosales’ personal 
recommendations.  We based our estimations on Dr. 
Rosales’ recommendations since he has the largest personal 
experience in injecting Dysport® for OMD. The review in 
question gathered its data from several sources which 
would have variation in its technique.  These various 
sources had limited experience regarding this particular 
medication in OMD. 
 
As is the case in any type of dystonia, the dosing range of 
botulinum toxin is broad.  We will separate subjects into 
three groups with a certain level of dosage: low, medium, 


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and high.  The study will start with a cohort of three 
subjects with OMD and inject using the low range of 
Dysport®.  After efficacy and safety is assessed 6 weeks 
later, it will be determined if it is appropriate to increase the 
dosage to the next level.  Safety alone, and not efficacy, 
will be the determinant on whether or not to proceed to the 
next dosing range although efficacy measure will be 
performed.  If determined to be safe, three additional 
subjects with OMD will be injected with the medium range. 
These subjects will be assessed 6 weeks later, and if 
determined to be safe, three more subjects will be injected 
at the high range.   This method will be utilized to assure 
safety at the particular dosages of Dypsort®. 
 
This optimal dosage will be the safest dosage that provides 
adequate efficacy. This will be based on the Clinical Global 
Impression Scale’s Efficacy Index[13]. Subjects from Aim 
1 will be offered enrollment into Aim 2. 
 
Aim 2: To determine the efficacy and safety of Dysport® 
for the treatment of oromandibular dystonia 
 
20 subjects will be included in the second part of the study 
and will be injected with the determined optimal dosage 
found at the end of the first study part.  They would be 
injected for Aim 2 after at least 12 weeks have passed, 
given that the effect from the prior injection had either 
completely abated or at least declined significantly.  The 9 
subjects from Aim 1 will be offered to enter study part 2 
unless they have severe adverse event (AE), ongoing AE or 
AE considered  inappropriatefor study continuation.  Their 
previous injections with Dysport® should not confound the 
results of Aim 2 since botulinum toxins Type A and 
Dysport® should both have minimal clinical effect at 12 
weeks out from injection.  Since the local population 
suffering from OMD is small, the inclusion of the Aim 1 
subjects into Aim 2 would lead to a much more rapid 
completion of recruitment. 
 
Amendment 2 January 26, 2015:  In the aim 1 protocol the 
result was that 2 of 3 of the first, lowest level, experienced 
adverse effects that were likely toxin related.  It was 
determined that it was not safe to move to level 2.  Since 
aim 2 will utilize the same dose as the completed aim 1 it is 
the plan to alter the number from 9 in part 1 and 20 in part 


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2 (total 29) to 3 in part 1 and 17 in part 2 total being 20 
subjects.  This will not alter the power of the study since 
that was passed on the 20 subjects in part 2.  In addition, for 
those in part 2, the option will be given to receive a second 
injection with an adjusted dose either up or down to their 
needs. 
 
In both Aim 1 and Aim2, the safety and efficacy will be 
recorded for all subjects that undergo injection.  All 
subjects will be examined and videotaped at the injection 
visit, then at 6 and 12 weeks after injection with a 
standardized protocol.  The primary outcome will be 
blinded examination scores of the videos performed after 
the study is complete. The evaluators will be two different 
movement disorders experts, not otherwise involved in the 
study, who will review the videotaped examinations, 
presented in a random order, using the Global Dystonia 
Rating scale (GDS) [14].  They will rate the dystonia at 
baseline (injection visit) and 6 weeks after injection.  The 
change in GDS score from baseline to 6 weeks after 
injection is the best objective measure of efficacy and will 
serve as the study’s primary endpoint.  We chose the GDS 
over other dystonia scales because of its ease of use, 
sensitivity to clinical changes because of its continuous 
rating system, internal consistency, and inter-rater 
reliability[14]. 
 
Secondary measures will include GDS scoring by blinded 
evaluation at 12 weeks after injection to assess duration of 
effect; GDS scoring by injecting practitioner at baseline, 6, 
and 12 weeks; Unified Dystonia Rating Scale (UDRS) [14] 
scoring of videos by the blinded evaluators, Clinical Global 
Impression at baseline and then along with the Efficacy 
Index at 6 and 12 weeks.  We will also assess a score from 
a patient completed questionnaire regarding interference 
with eating, swallowing, drooling, speaking, pain, and 
quality of life. 
 
 
Study Objectives: 
Study subjects will be patients with symptoms of OMD 
seen in our practice who warrant therapy with botulinum 
toxin injection. This study plans for 9 patients to complete 
Aim 1 of the study and 20 patients (not necessarily 
different patients) to complete Aim 2. 


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Amendment 2 January 26, 2015: the number is altered 3 in 
aim 1 and 17 in aim 2. 
 
Primary: Standardized assessments (including the video) will be 
completed at baseline prior to injection and at weeks 6 and 12. 
The patient will be objectively evaluated by 2 blinded video 
raters as well as the injecting physician in face-to-face clinical 
examination.  All raters will be movement disorder experts with 
experience in evaluating dystonias. 
 
The standardized video protocol will be as follows: 
a. Subject looks at camera and rests with eyes open for 10 
seconds 
b. Subject looks at camera and rests with eyes closed for 10 
seconds 
c. Opening and closing mouth three times each from front 
view, lateral view from right, lateral view from left 
d. Subject opens mouth with tongue resting in floor of 
mouth for 10 seconds 
e. Subject opens mouth with tongue protruding for 10 
seconds 
f. Reading the “Grandfather Passage” 
g. Having a conversation 
h. Eating two crackers without water, swallowing bolus of 
food 
i. 
Drinking water from a cup 
j. 
Subject has mouth closed and at rest, but performing 
tasks that may activate OMD: 5 seconds of tapping the 
thumbs to the index fingers and 5 seconds of opening 
and closing each hand 
 
Rating will be evaluated by “Lower face” and “Jaw and tongue” 
sections in the Global Dystonia Severity Rating Scale (GDS) for 
a maximal severity score of 10 in each section and 20 total. 
This assessment will be completed by the injector live and by the 
blinded raters viewing the video. The Ipsen reviewers had 
initially requested a change in the GDS that would be considered 
clinically significant.  Based on our experience, a change of 2 or 
more points in a certain section marks a significant change in the 
patient’s condition. We will be able to further validate this by 
correlating it with all of the subjective measures we will be 
gathering. 


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Subjects will also be rated by the Unified Dystonia Rating Scale 
by blinded raters via video and injectors live. 
 
Secondary: The patients will be evaluated subjectively by 
questionnaire.  Evaluations will be performed at baseline (day of 
injection), 6, and 12 weeks after injection. Drooling and 
chewing/swallowing scales are not specifically designed for 
dystonia, but are well validated and are appropriate for 
quantifying symptom severity in OMD. 
1. Measure of jaw pain by visual analogue scale (0-100) 
2. Drooling (SCS-PD [19]) 
3. Tendency for tongue biting (estimated number of tongue 
bites per day) 
4. Ease of chewing and  swallowing (SDQ [20], modified 
to exclude questions 5, which is redundant since it 
regards drooling and question 15 which is not relevant to 
the study as it involves prior aspiration pneumonias) 
5. Ease of speaking: Fahn-Marsden Scale Part B “Speech” 
question [21] 
6. Quality of Life: Oromandibular dystonia questionnaire 
(OMDQ-25) [22] 
7. Global Clinical Impression Scale (CGI) with Efficacy 
Index [13] 
 
Statistical analysis: 
This is a pilot study.  Subjects will be their own controls. 
The primary end point will be the change in the GDS from 
baseline to week 6 based on the blinded video review. 
Analysis will be performed with a standard t-test. 
 
Secondary measures will also examine change of subjective 
symptoms from baseline to weeks 6 and 12 including 
questionnaire scores of pain, quality of life, drooling, 
tongue biting, chewing, swallowing and speaking as 
delineated above.  GDS from the injecting practitioner at 
the injection visit, week 6, and week 12 will be measured as 
will the blinded video raters’ GDS score at 12 weeks. 
UDRS will also be rated at baseline, 6 weeks, and 12 weeks 
by blinded evaluators of the videos. CGI will be performed 
at baseline to determine the severity of the dystonia and 
then at weeks 6 and 12 to determine the safety and efficacy 
of the injections. 
 
Study Sites: 


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Emory University Movement Disorders Clinic only 
 
Timeline: 
This study will be completed within two years. 
 
References: 
1. 
Weiner, W.J. and E. Tolosa, Hyperkinetic movement 
disorders. Handbook of clinical neurology. 2011, 
Edinburgh: Elsevier. p. 
2. 
Stacy, M.A., Handbook of dystonia. Neurological 
disease and therapy. 2007, New York: Informa 
Healthcare. xvii, 412 p., 1 leaf of plates. 
3. 
Tan, E.K. and J. Jankovic, Botulinum toxin A in patients 
with oromandibular dystonia: long-term follow-up. 
Neurology, 1999. 53(9): p. 2102-7. 
4. 
Fahn, S., J. Jankovic, and M. Hallett, Principles and 
practice of movement disorders. 2nd ed. 2011, 
Edinburgh ; New York: Elsevier/Saunders. vii, 548 p. 
5. 
Nutt, J.G., et al., Epidemiology of dystonia in Rochester, 
Minnesota. Adv Neurol, 1988. 50: p. 361-5. 
6. 
Jankovic, J. and J. Orman, Blepharospasm: demographic 
and clinical survey of 250 patients. Ann Ophthalmol, 
1984. 16(4): p. 371-6. 
7. 
Asgeirsson, H., et al., Prevalence study of primary 
dystonia in Iceland. Mov Disord, 2006. 21(3): p. 293-8. 
8. 
Le, K.D., B. Nilsen, and E. Dietrichs, Prevalence of 
primary focal and segmental dystonia in Oslo. 
Neurology, 2003. 61(9): p. 1294-6. 
9. 
Batla, A., M. Stamelou, and K.P. Bhatia, Treatment of 
focal dystonia. Curr Treat Options Neurol, 2012. 14(3): 
p. 213-29. 
10. 
Rosales, R.L., et al., The broadening application of 
chemodenervation in X-linked dystonia-parkinsonism 
(Part II): an open-label experience with botulinum toxin- 
A (Dysport(R)) injections for oromandibular, lingual, 
and truncal-axial dystonias. Int J Neurosci, 2011. 121 
Suppl 1: p. 44-56. 
 
11. 
Van den Bergh, P., et al., Five-year experience in the 
treatment of focal movement disorders with low-dose 
Dysport botulinum toxin. Muscle Nerve, 1995. 18(7): p. 
720-9. 
12. 
Bhidayasiri, R., F. Cardoso, and D.D. Truong, Botulinum 
toxin in blepharospasm and oromandibular dystonia: 
comparing different botulinum toxin preparations. Eur J 
Neurol, 2006. 13 Suppl 1: p. 21-9. 
13. 
Guy, W., ed. Clinical global impression. ECDEU 
Assessment Manual for Psychopharmacology, ed. W. 
Guy. 1976, DHEW: Rockville, Maryland: National 


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Institute of Mental Health. 
14. 
Comella, C.L., et al., Rating scales for dystonia: a 
multicenter assessment. Mov Disord, 2003. 18(3): p. 
303-12. 
19. 
Perez Lloret, S., et al., Validation of a new scale for the 
evaluation of sialorrhea in patients with Parkinson's 
disease. Mov Disord, 2007. 22(1): p. 107-11. 
20. 
Manor, Y., et al., Validation of a swallowing disturbance 
questionnaire for detecting dysphagia in patients with 
Parkinson's disease. Mov Disord, 2007. 22(13): p. 1917- 
21. 
21. 
Burke, R.E., et al., Validity and reliability of a rating 
scale for the primary torsion dystonias. Neurology, 
1985. 35(1): p. 73-7. 
22. 
Merz, R.I., J. Deakin, and M.R. Hawthorne, 
Oromandibular dystonia questionnaire (OMDQ-25): a 
valid and reliable instrument for measuring health- 
related quality of life. Clin Otolaryngol, 2010. 35(5): p. 
390-6. 
STUDY POPULATION : 
Sample size calculation: 
Power and Sample Size Analysis: This is a pilot study 
therefore does not require a power analysis 
Inclusion and exclusion criteria: 
Eligible OMD patients will be asked to join the study. If 
interested, they will be properly consented with an IRB 
approved consent form. 
Inclusion criteria: Patients will be included if they meet 
the following inclusion criteria: a diagnosis of primary or 
tardive OMD; moderate or severe severity, defined as GDS 
score ≥4 in either “lower face” or “jaw and tongue” section; 
age>18 years; and capability of attending the scheduled 
visits. Candidates are only those who have been previously 
injected with any botulinum toxin type A and responded to 
that treatment, and are at least 12 weeks post last injection. 
Women of childbearing age need to use contraception in 
order to be included. 
Exclusion criteria: Existence of a systemic disease that 
could confound the evaluation; previous placement of Deep 
Brain Stimulation electrodes to treat dystonia; concomitant 
oral medications that could interfere with the action of BTX 


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Type A (e.g., aminoglycosides), on an unstable dosage of 
any medication prescribed to treat dystonia (e.g., 
benzodiazepines, baclofen or anticholinergics), any known 
hypersensitivity to any botulinum toxin preparation and 
allergy to cow’s milk protein, immunoresistance to other 
forms of botulinum toxin type A, existence of a 
concomitant neuromuscular disorder (e.g., Myasthenia 
Gravis or Lambert-Eaton syndrome, etc); infection at the 
proposed injection sites; pregnant women; women of 
childbearing age NOT on contraception, breastfeeding 
women, inability to comply with scheduled visits; and 
patients who had been previously injected but who did not 
respond. 
INVESTIGATIONAL 
MEDICINAL PRODUCT : 
Dysport® (AbobotulinumtoxinA), provided by Ipsen: 1 
injection cycle for each group and each study part. 
Location of injections will be determined by the clinician to 
treat the particular dystonic symptom and documented in 
the source document.  Muscle choice will be at the 
discretion of the injector but will follow the injection 
technique from Table 1 and dosing guidelines from Table 
2.  There will be two expert practitioners performing the 
injections using EMG guidance. Each practitioner will stay 
with the patient for the duration of the study.  Dysport® 
will be reconstituted at a concentration of 1.5 cc of normal 
saline/300 units. 
Table 1: Injection techniques that will be used in study: 
Lateral 
Pterygoid 
Using the technique as described by 
Barbano, 2007  [15]. Under EMG 
guidance. The needle will be inserted 
into the notch inferior to the 
zygomatic arch and in between the 
condylar and coronoid processes in 
the mandibular ramus. 
Medial 
Pterygoid 
Using technique by Brin et al [16]. 
Under EMG guidance.  Needle is 
inserted beneath the angle of the 
mandible, angled superiorly and 
anteriorly to hug the inside of the 
mandible. 
Anterior 
digastrics 
Using technique by Esper et al [17]. 
The patient is supine with the head 
tilted back. The placement of the 
needle is approximately two 


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fingerbreadths back from the midline 
of the body of the mandible and 1-2 
cm lateral. The needle is placed, with 
EMG guidance, into the digastric 
muscle. 
Masseter 
Under EMG guidance. The needle is 
inserted where the muscle can be 
palpated over the inferior mandibular 
ramus.  As in Cardoso et al [18]. 
Genioglossus 
Under EMG guidance.  Needle is 
directed one finger breadth laterally 
from midline of mandible and one 
finger breadth posterior. As in Esper 
et al [17]. 
References: 
15. 
Barbano, R.L., Handbook of dystonia. Neurological 
disease and therapy, ed. M.A. Stacy. 2007, New York: 
Informa Healthcare. xvii, 412 p., 1 leaf of plates. 
16. 
Brin, M.F., F. Danisi, and A. Blitzer, Handbook of 
botulinum toxin treatment. 2nd ed, ed. P. Moore and M. 
Naumann. 2003, Malden, Mass.: Blackwell Science. xii, 
463 p. 
17. 
Esper, C.D., A. Freeman, and S.A. Factor, Lingual 
protrusion dystonia: frequency, etiology and botulinum 
toxin therapy. Parkinsonism Relat Disord, 2010. 16(7): 
p. 438-41. 
18. 
Cardoso, F., R. Bhidayasiri, and D. Truong, Manual of 
botulinum toxin therapy, ed. D. Truong, D. Dressler, and 
M. Hallett. 2009, Cambridge, UK ; New York: 
Cambridge University Press. xvi, 218 p. 
Table 2: Doses of Dysport® per muscle if selected for 
injection: 
Muscles that may be included for in injection for OMD 
with Jaw Closing: 
1st cohort of 
2nd   cohort 
3rd   cohort 
subjects 
of subjects 
of subjects 
Medial 
50 
75 
100 
Pterygoid 
Masseter 
25 
50 
75 
Muscles that may be included in injection for OMD with 
Jaw Opening 
1st cohort of 
subjects 
2nd   cohort 
of subjects 
3rd   cohort 
of subjects 


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Lateral 
50 
75 
100 
Pterygoid 
Anterior 
10 
20 
30 
digastrics 
Muscle that will be included in injection for OMD with 
Tongue Protrusion 
*After 10 subjects were completed it appeared 15 units was 
too high as four developed dysphagia and dysarthria. 
Starting on subject 11 this will be cut to 7.5 units 
STUDY ENDPOINTS : 
PRIMARY EFFICACY 
ENDPOINT : 
For study Part 2: 
The primary end point will be the change in the GLOBAL 
DYSTONIA RATING SCALE (GDS) from baseline to week 6 
based on the blinded video review. 
SECONDARY EFFICACY 
ENDPOINT 
(IF APPLICABLE) : 
For study Part 2: 
Secondary measures will examine change of subjective 
symptoms from baseline to weeks 6 and 12 including 
questionnaire scores of pain, quality of life, drooling, 
tongue biting, chewing, swallowing and speaking as 
delineated above.  GDS from the injecting practitioner at 
the injection visit, week 6, and week 12 will be measured as 
will the blinded video raters’ GDS score at 12 weeks. 
UDRS will also be rated at baseline, 6 weeks, and 12 weeks 
by blinded evaluators of the videos. CGI will be performed 
at baseline to determine the severity of the dystonia and 
then at weeks 6 and 12 to determine the safety and efficacy 
of the injections. 
Exploratory endpoints: assessments (previous measures) for 
jaw opening and jaw closing groups. 
SAFETY ENDPOINTS AND 
EVALUATIONS : 
Collection of AEs will be done throughout both study 
parts. 
These evaluations will be made by the study coordinator 
in-person at the injection visit, weeks 6, and 12 and also 
by phone conversation with the patient at weeks 2 and 
4. 
Definition of some potential AEs: 
1st cohort 
of subjects 
2nd   cohort 
of subjects 
3rd   cohort 
of subjects 
Genioglossus 
7.5* 
25 
35 


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-Swallowing: any choking or aspiration. 
-Chewing: losing ability to chew something that subject 
could before the injections. 
-Soft palate incompetence: fluid leaking out from mouth 
through the nose. 
-Speaking: worse than baseline speech. 
PEC RECOMMENDATION 
ON STUDY 
□ NO OBJECTION 
□ NO OBJECTION WITH RECOMMENDATIONS : 
Please enter recommendations below : 
□ REJECTION 
Please enter below justification for rejection : 
DEVELOPMENT 
COMMITTEE 
STATEMENT 
□ NO OBJECTION 
□ NO OBJECTION WITH SUGGESTIONS : 
Please enter suggestions below : 
□ REJECTION 
Please enter below justification for rejection : 


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APPENDIX 1: 
The Global Dystonia Severity Rating Scale (tailored for OMD) 
 
The global score is an overall score for the body area. The investigator rates the patient in 
relationship to all patients. If the dystonia changes during the examination, the rating for the 
maximal dystonia is recorded. 
 
Each body area is rated from 0 to 10: 
 
 
0 
No dystonia present in that body area 
 
1 
Minimal dystonia 
 
5 
Moderate dystonia 
 
10 
Most severe dystonia 
 
Two body areas will be tested, each on a 0-10 scale: 1. lower face and 2. Jaw and tongue 
 
Note: The aggregate score will be on a range from 0-20 (in order to meet inclusion criteria, 
subject must have at least a 4 in at least one of the affected body parts). 
 
APPENDIX 2 
 
The Unified Dystonia Rating Scale (UDRS) (tailored for OMD) 
 
Factor/area Criteria 
Duration 
0 None 
0.5 Occasional (_25% of the time); predominantly submaximal 
1.0 Occasional (_25% of the time); predominantly maximal 
1.5 Intermittent (25–50% of the time); predominantly submaximal 


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2.0 Intermittent (25–50% of the time); predominantly maximal 
2.5 Frequent (50–75% of the time); predominantly submaximal 
3.0 Frequent (50–75% of the time); predominantly maximal 
3.5 Constant (_75% of the time); predominantly submaximal 
4.0 Constant (_75% of the time); predominantly maximal 
Motor severity 
 
Lower face 
0 None 
1 Mild: grimacing of lower face with minimal distortion of mouth (_25% maximal) 
2 Moderate: grimacing of lower face with moderate distortion of mouth (_25% but _50% 
Maximal) 
3 Severe: marked grimacing with severe distortion of mouth (_50% but _75% maximal) 
4 Extreme: intense grimacing with extreme distortion of mouth (_75% maximal) 
Jaw and tongue 
0 None 
1 Mild: jaw opening or tongue protrusion _25% of possible range or forced jaw clenching 
Without bruxism 
2 Moderate: jaw opening or tongue protrusion _25% but _50% of possible range or forced jaw 
Clenching with mild bruxism secondary to dystonia 
3 Severe: jaw opening and/or tongue protrusion _50% but _75% of possible range or forced jaw 
Clenching with pronounced bruxism secondary to dystonia 
4 Extreme: jaw opening or tongue protrusion _75% of possible range or forced jaw clenching 
with inability to open mouth 
 
 
APPENDIX 3 
Sialorrhea Clinical Scale for PD (SCS-PD) ( from Perez et al. [19]): 
 
Please read the following questions and try to answer them on the 
basis of how you felt during the past week. 
 
A. During the day, when do you feel there is more saliva in your 
mouth? 
1- Never. 
2- At meal times. 
3- Throughout the day, not related to meals. 
3- All the time, even when I am asleep. 
 
B. When you are asleep, how much saliva is there in your mouth? 
0- I don’t notice an increase in saliva. 
1- I notice increased amounts of saliva in my mouth, but my pillow 
doesn’t get wet. 
2- My pillow gets wet. 
3- My pillow and other bedclothes get wet. 


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C. While you are awake, 
0- I don’t drool. 
1- Saliva wets my lips. 
2- Saliva accumulates on my lips, but I don’t drool. 
3- I drool. 
 
D. Does accumulation of saliva in your mouth impair your speech? 
0- No. 
1- I must swallow frequently to avoid difficulties. 
2- I have trouble speaking. 
3- I can’t speak at all. 
 
 
 
 
E. Does accumulation of saliva in your mouth impair your eating 
ability? 
1- No. 
2- I must swallow frequently to avoid difficulties. 
2- I have trouble eating. 
3- I can’t eat at all. 
 
F. How many times do you drool during the daytime? 
0- Never. 
1- Not more than 3 times. 
2- Often. I have to carry a handkerchief with me all the time. 
3- Permanently. 
 
G. When you go out or on social occasions, does saliva accumulation 
bother you? 
1- No. 
2- I notice an accumulation, but it does not bother me. 
3- I realize other people notice it, but I can control the situation (for 
example, with a handkerchief). 
4- I have stopped attending social meetings. 
 
 
APPENDIX 4 
Swallowing Disturbance Questionnaire [20] (without questions 5 and 15) 
 
 
Questions 
Never=0 
Seldom (once a 
month or less)=1 
Frequently (1-7 
times per week)=2 
Very frequently 
(more than 7 times a 
week)=3 
1. Do you experience 
difficulty chewing solid 


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food like an apple, 
cookie or a cracker? 
2. Are there any food 
residues in your mouth, 
cheeks, 
under your tongue or 
stuck to your palate after 
swallowing? 
3. Does food or liquid 
come out of your nose 
when you eat or 
drink? 
4. Does chewed up food 
dribble from your mouth? 
6. Do you swallow 
chewed up food several 
times before it goes 
down your throat? 
7. Do you experience 
difficulty in swallowing 
solid food (i.e., do 
apples or crackers get 
stuck in your throat)? 
8. Do you experience 
difficulty in swallowing 
pureed food? 
9. While eating, do you 
feel as if a lump of food is 
stuck in 
your throat? 
10. Do you cough while 
swallowing liquids? 
11. Do you cough while 
swallowing solid foods? 
12. Immediately after 
eating or drinking, do you 
experience a 
change in your voice, 
such as hoarseness or 
reduced? 
13. Other than during 
meals, do you experience 
coughing or 
difficulty breathing as a 
result of saliva entering 
your windpipe? 
14. Do you experience 
difficulty in breathing 
during meals? 
 
 
APPENDIX 5: 
From: Fahn-Marsden Dystonia Rating Scale [21] 
 
Part B “Speech” question 
0=Normal 
1=Slightly involved, easily understood 
2=Some difficulty understanding 
3=Marked difficulty understanding 
4=Complete or almost complete anarthria 


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APPENDIX 6: 
Oromandibular Dystonia Questionnaire (OMDQ-25) 
Please answer the following questions according to your problems with oromandibular dystonia 
in the past two weeks. Mark or tick only one answer per question and ensure to complete all 25 
questions. 
 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
22. Have you had problems with nasal regurgitation from your disease? 
21. Have you had problems getting understood when talking in public or in loud surroundings? 
20. Have you had problems getting understood when in quiet surroundings? 
19. Have you had problems getting understood when talking on the telephone? 
18. Have you taken painkillers because of this? 
17. Have you had pain in the face, head or neck? 
16. Have you injured your tongue, lips or cheeks while eating? 
15. How often have you dropped food or drink onto your clothes while eating? 
14. Have you preferred to eat alone because of your dystonia? 
13. Have you avoided going out for dinners, e.g. a restaurant or a pub? 
12. How often have you had problems keeping your tongue in your mouth? 
11. Have you felt embarrassed or ashamed because of your look/ outer appearance? 
10. How often have you complained about grimacing? 
9. How often has your dystonia affected your outer appearance? 
8. Have you had problems with close friends or your family because of your dystonia? 
7. Have you felt insecure while being in public? 
6. Have you avoided situations where many people are present? 
5. Have you felt angry or annoyed? 
4. Have you felt down and/ or depressed? 
3. Have you felt lonely or isolated because of your dystonia? 
2. Has your work or housework been affected by the disease? 
1. How often has oromandibular dystonia affected your everyday life? 


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Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
Never – Seldom – Sometimes – Often – Always 
 
 
 
APPENDIX 7: 
Clinical Global Impression Scale [13] 
CLINICAL GLOBAL IMPRESSION SCALE 
1. Severity of Illness of Disease Under Study 
Considering your total clinical experience with this particular population, how incapacitated has 
the subject been within the last week? 
0=Not assessed 
1=Normal, not at all incapacitated 
2=Borderline incapacitated 
3=Mildly incapacitated 
4=Moderately incapacitated 
5=Markedly incapacitated 
6=Severely incapacitated 
7=Among the most extremely incapacitated 
subjects 
 
 
2. Global Improvement 
Rate total improvement whether or not, in your judgment, it is due entirely to drug treatment. 
Compared to baseline, how much has the subject changed? 
0=Not assessed 
1=Very much improved 
2=Much improved 
3=Minimally improved 
4=No change 
5=Minimally worse 
6=Much worse 
7=Very much worse 
25. How often have you had to drink to enable swallowing? 
24. Have you had to watch the consistency of the food before eating it? 
23. Has it been difficult for you to keep food in your mouth while chewing or swallowing? 


 
 
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3. Efficacy index-Rate this item on the basis of DRUG EFFECT ONLY 
Select the terms which best describe the degrees of therapeutic effect and side effects and 
record the number in the box where the two items intersect. This is scored as Therapeutic 
effect score divided by the side effect score. 
Side effects 
Therapeutic 
effect 
None 
(1) 
Do not significantly 
interfere with 
subject’s 
functioning (2) 
Significantly 
interferes with 
subject’s 
functioning (3) 
Outweighs 
therapeutic effect 
(4) 
MARKED-Vast 
improvement. 
Complete or nearly 
complete remission 
of all symptoms (4) 
4/1=4 
4/2=2 
4/3=1.33 
4/4=1 
MODERATE- 
Decided 
improvement. Partial 
remission of 
symptoms (3) 
3/1=3 
3/2=1.5 
3/3=1 
3/4=0.75 
MINIMAL-Slight 
improvement which 
doesn’t alter status of 
care of subject (2) 
2/1=2 
2/2=1 
2/3=0.67 
2/4=0.5 
UNCHANGED OR 
WORSE (1) 
1/1=1 
1/2=0.5 
1/3=0.33 
1/4=0.25 
NOT ASSESSED 
(0)) 
0 
0 
0 
0