Dystonia Treatment With Injections Supplemented By Transcranial Magnetic Stimulation
Phase: NA
Conditions: Cervical Dystonia
Sponsor: University of Florida

 NCT04916444 
 
Title:  Dystonia Treatment With Injections Supplemented By Transcranial Magnetic Stimulation 
 
Document Date: 6/17/2022 

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IRB Research Protocol 
Title: Dystonia Treatment With Injections Supplemented by TMS: the D-TWIST study 
Principal Investigator: John Yu, MD 
Faculty Mentor for Student PI and Co-Investigator: Aparna Wagle Shukla, MD   
Other Study Personnel: Coralie de Hemptinne, PhD; Jackson Cagle, PhD; Julie Segura; Manahil Wajid; Liam 
Kugler; Kara Johnson, PhD; Janine Lopes; Lauren Fanty, MD; Jessica Frey, MD 
Background: Dystonia is a hyperkinetic movement disorder defined by excessive, involuntary, and often 
painful muscle contractions.1,2 The most common form of adult-onset isolated dystonia is cervical dystonia.3 In 
addition to pain and abnormal posture, dystonia is associated with non-motor symptoms such as increased 
rates of depression, anxiety, and cognitive changes. There is also evidence to show clinical and subclinical gait 
changes in dystonia. 4-8 Currently, the gold standard treatment for dystonia is botulinum toxin (BoNT) injections 
administered every 12 weeks to affected muscle groups.9-11 However, these injections can be painful, can be 
complicated by side effects such as dysphagia and neck weakness, and patients commonly report that the 
benefits of BoNT do not last the entire 12 weeks.11  In a retrospective analysis of dystonia patients injected at 
our center (n = 150), we found the average duration of benefit was about 9.5 weeks, which was similar to 
reports by other studies.12,13 Also, BoNT treatment provides only pure symptomatic motor benefits and does 
not modify the disease pathophysiology.14-16 Other treatment options such as deep brain stimulation may be 
effective for some types of dystonia, but it is an invasive procedure and not all patients are appropriate 
candidates for this surgery.2,9 Therefore, there is clear merit in exploring other options to potentiate and 
possibly prolong the benefits of BoNT therapy.  
 
Transcranial magnetic stimulation (TMS) is a painless and non-invasive neuromodulation technique that uses a 
magnetic field to induce an electric field in the cortex. TMS pulses delivered on a repetitive basis known as 
repetitive TMS (rTMS) has the ability to modulate dystonia networks and lead to clinical improvements. rTMS 
delivered at low-frequency (≤ 1 Hz) mimics long-term depression, leading to decreased cortical excitability, 
while high-frequency TMS (> 5 Hz) mimics long-term potentiation, leading to increased cortical excitability.10,17 
rTMS delivered over multiple sessions has cumulative benefits which last beyond the stimulation period.9,10 
rTMS effects extend beyond the area targeted for stimulation and can influence remote brain regions.   
 
Dystonia is a network disorder involving the motor cortex, premotor cortex, and their connections with other 
brain regions. The therapeutic role of rTMS in dystonia has been investigated in only a few studies, which 
employed low-frequency stimulation parameters and found the dorsal premotor cortex (dPMC) as an important 
brain target for modulation of the dystonia network.11 These studies mostly focused on patients with arm and 
hand dystonia, even though cervical dystonia is the most common form of dystonia.18-21 Furthermore, these 
studies were small, many involved only a single session of rTMS, the follow-up time period was limited, and 
they have yet to investigate the interactions between BoNT and rTMS as a potential adjuvant therapy. Finally, 
rTMS targeted to the dystonia network is likely to influence motor and non-motor symptoms such as 
depression, anxiety, and cognitive impairment; however clinical studies conducted so far have not assessed 
non-motor benefits.17 
 
The primary goal of the proposed study is to determine whether low-frequency rTMS delivered to the dPMC 
has synergism with BoNT therapy in patients with isolated cervical dystonia. We will determine whether rTMS 
serves as a therapeutic bridge for early fading of BoNT benefits (Aim 1). We will select patients receiving 
BoNT injections every 12 weeks but endorsing clinical benefits lasting < 9 weeks. We will initiate active versus 
sham rTMS therapy in a crossover design at 9 weeks after receiving BoNT injections. We will measure the 
effects at baseline or prior to the first TMS session (T0), immediately after (T1) and 2 weeks after (T2) rTMS 
(Figure 1). The T2 visit will coincide with their next round of botulinum toxin injections (this study visit will be 
approximately 12 weeks after their initial BoNT injection. The participants will then undergo the same exact 
study protocol but will have either active or sham rTMS (whichever treatment they were not assigned to in the 
first round). As the rTMS therapy requires multiple sessions spanning weeks for cumulative benefits, feasibility 

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and compliance for completion of therapy can be challenging. We therefore propose an accelerated rTMS 
protocol which will condense multiple sessions into 4 consecutive days. Accelerated rTMS protocols have 
shown success and safety in other patient populations22-24, but have not yet been studied in dystonia. In 
addition, the crossover design will be feasible because these patients are already traveling to UF clinic for 
botulinum toxin injections every 12 weeks as part of their standard of care, so most if not all will live within an 
acceptable driving distance for them to complete the protocol.  
 
In addition to clinical outcomes, we will investigate the physiological changes underlying the clinical effects 
(Aim 2). Single-pulse and paired-pulse studies in patients with dystonia have revealed inhibitory dysfunction, 
particularly increased motor evoked potential (MEP), prolonged cortical silent period (CSP), and reduced short 
intracortical inhibition (SICI).25-30 These findings implicate a primary dysfunction of the motor cortex. To further 
understand the motor cortex functions, we recently employed high-density electroencephalogram (HD-EEG) 
techniques. We found there was an impaired cortical desynchronization in the alpha and beta bands during 
voluntary movement in patients with cervical dystonia.31  
 
OBJECTIVES/SPECIFIC AIMS: 
Specific Aim #1: Determine the Clinical effects of rTMS combined with BoNT in isolated cervical 
dystonia. We will determine the clinical effects of active vs. sham rTMS on motor, non-motor, and gait 
symptoms. We will examine the motor effects with the standardized Toronto Western Spasmodic Torticollis 
Rating Scale (TWSTRS), mood with the Beck Depression Inventory, cognition with the Wisconsin Card Sorting 
Task and Trail Making Test, and gait with the instrumented Zeno walkway system. We hypothesize there will 
be greater improvement in the motor (primary outcome), nonmotor, and gait measures (secondary outcomes) 
at T1, and T2 compared to baseline in the active rTMS group compared to the sham rTMS group. 
Specific Aim #2: Determine the Physiological effects of rTMS combined with BoNT in isolated cervical 
dystonia. We will determine the physiological effects of active vs. sham rTMS using TMS and EEG 
techniques. We will examine the cortical excitability with established TMS parameters including MEP, CSP, 
and SICI, and we will examine cortical desynchronization of alpha and beta band with resting state HD-EEG. 
We hypothesize that the change in TMS measures and EEG measures at T1, and T2 compared to baseline 
will significantly improve in the active rTMS group compared to the sham rTMS group and will correlate with 
the clinical improvements as outlined in specific Aim #1. 
RESEARCH PLAN AND METHODOLOGY: Patients with a diagnosis of isolated cervical dystonia receiving 
BoNT every 12 weeks at our movement disorders center will be enrolled. Diagnosis of cervical dystonia will be 
established in accordance with the Consensus Statement of the Movement Disorders Society.1  
 
Inclusion Criteria: patients 18-85 years of age who receive regular BoNT scheduled every 12 weeks, on 
stable optimized doses but with reported benefits lasting ≤ 9 weeks for 2 consecutive cycles. Patents followed 
at our center routinely fill out a self-reported form to document the duration of benefits perceived with BoNT 
therapy. Participants will be allowed to continue oral medications that they are taking for dystonia concurrently 
and will be encouraged to continue this regimen throughout the duration of the study . 
Exclusion Criteria: 1) Presence of metallic objects or neurostimulators in the brain (including the following: 
cochlear implants, implanted electrodes/stimulators such as deep brain stimulators and vagus nerve 
stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry and hair barrettes) , 2) pregnancy, 
3) history of active seizures or epilepsy, 4) patients with severe scoliosis or other gait impairment that will 
preclude them from participating in gait evaluation. 
Enrollment: Our target is to enroll 10 total patients in the study in a crossover design, with all 10 patients 
receiving both active and sham rTMS in blinded, random order. In order to enroll 10, we will need to screen 
more than that number. We anticipate that we will need to screen 20 patients in order to find 10 that are eligible 
for enrollment. Of those 20, we anticipate that 10 will enroll but later choose not participate in the study.   

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IRB approved informed consent will be obtained. The study procedures will be explained, and subjects will 
have a detailed medical history and neurological examination. Patients will be randomly assigned to receive 
either active or sham stimulation first (S1), and will then crossover and switch to the other treatment type 
during the second session (S2). Patients will have primary and secondary outcome measures performed at 
three time points: Baseline (T0), following rTMS (T1), and 2 weeks after rTMS (T2) (Figure 1). Patients will 
have the next round of regularly scheduled botulinum toxin injections during the T2 study visit, after the 
outcome measures have been obtained. Then the entire study protocol will be performed again but the patients 
will undergo either active or sham rTMS during S2 (whichever option they were not exposed to during S1). The 
study protocol will take place over approximately 24 weeks. Details of specific parts of the protocol are 
included below.  
 
 
Primary Outcome: Motor symptoms of dystonia will be measured with TWSTRS; a widely accepted 
composite rating scale for cervical dystonia with subscales for clinical severity, functional disability, and 
associated pain. We will record videos of subjects at baseline and follow-up time points, which will be scored 
by two independent blinded raters.  
Secondary Outcomes: Non-motor symptoms will be measured as follows: mood with the Beck Depression 
Inventory (BDI) and cognitive tasks as measured by the Wisconsin Card Sorting Task (WCST) and Trail 
Making Test (TMT); gait  with Zeno walkways system for temporal parameters (stance time, double support 
time, stride time, and cadence), spatial parameters (stride length, step width, step length, step asymmetry), 
and the dynamic stability index (ratio between single and double support time)4,5; physiological outcomes will 
be measured with standard procedures for TMS based MEP, CSP, and SICI25-30 and HD-EEG based power of 
alpha and beta bands during resting state.31 
 
Randomization: A random number generator will be used to assign patients to active or sham stimulation 
during the S1 time period. If the number is even, the patient will be assigned active stimulation. If the number is 
odd, the patient will be assigned sham stimulation. The study team member who makes these assignments will 
be aware of which patients are receiving active or sham stimulation but will be different from the blinded 
reviewer. The blinded reviewer will be unaware of the patient’s assignment to active or sham stimulation. 
Following crossover, the patients will undergo whichever treatment condition (active or sham) they were not 
exposed to during S1.  
 

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rTMS protocol: rTMS will be delivered using a NeuroStar TMS therapy system (Neuronetics, Malvern, PA). 
The resting motor threshold (RMT) will be defined as the lowest stimulation intensity required to evoke a 50 μV 
potential in a target muscle (i.e. first dorsal interosseus muscle/FDI). A figure of eight coil will be used to deliver 
the stimulation. Patients will be seated in a comfortable reclined chair. The dPMC target will be defined as 1 
cm medial and 2 cm anterior to the site of RMT acquisition.11 The rTMS protocol will be as follows: each 
session will consist of 1-Hz rTMS over the dPMC for 30 minutes (1800 pulses) at 90% of the RMT. Patients will 
receive 4 sessions per day for 4 consecutive days with a 10-minute break between each session. Daily 
duration of the rTMS protocol, including breaks, will last approximately 160 minutes. Constant coil position will 
be continuously monitored during the experiment. During rTMS, all participants will wear earplugs in order to 
protect the ears from the acoustic artefact associated with the discharge of the stimulation coil.  
 
Sham protocol: Participants will undergo the same procedure for identifying target location and RMT used in 
patients receiving real rTMS. Simulated rTMS will be administered using a NeuroStar sham coil, which 
produces discharge noise and vibration without stimulating the cerebral cortex. This technique has been 
suggested to provide more effective blinding compared to other methods use in previous controlled studies.17 
Although the physician administering TMS will be aware of the status of the subject in terms of real TMS 
versus sham TMS, this physician will play no role in any of the outcome measures, and will not be present 
during any of the outcome measure assessments. Similarly, the investigator who performs the outcome 
measures will not be present during any of the TMS sessions, and therefore will remain blinded to the status of 
the patients with respect to real rTMS versus sham rTMS.  
 
Single and paired-pulse TMS paradigms: A MagStim BiStim device (Whitland, UK) will be used for the 
single and paired-pulse TMS paradigms. These will be followed per established protocols in the literature 
(Figure 2 A and C).10 A single-pulse of TMS will be targeted over the motor cortex to generate a motor evoked 
potential (MEP), which can be captured on EMG. The rest of the EMG will be analyzed to assess the time 
between the TMS pulse and the MEP (also known as the latency) and the amount of time muscle activity 
remains silent following 
the MEP (also known as 
the cortical silent period). 
In a paired-pulse TMS 
paradigm, a subthreshold 
pulse will be provided 
followed by an 
interstimulus interval and 
then subsequent delivery 
of a suprathreshold pulse. 
When the interstimulus 
interval is short (1-4 
msec), the ratio of MEP 
amplitudes produced by 
these two pulses is known 
as short interval 
intracortical inhibition 
(SICI). 
 
EEG protocol: High-
Density EEG using 128 
electrodes as the setup 
will be implemented. Each 
EEG session should last about 1 hour. Patients will be seated comfortably in a chair and a cap will be 
stretched across the scalp. This cap has 128 contacts where the electrodes will be connected using biosoluble 
glue. The electrodes will be placed appropriately by a clinician or technician trained to place the EEG 
electrodes. The patient’s electrical activity will be recorded under two conditions: at rest and with maximal 

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range of motion/excursion in six directions: up, down, left, right, left shoulder, right shoulder. Patients will also 
be instructed to perform arm movements while the EEG is recording. A sensor such as the Delsys system will 
be used to measure the patient’s motion at the neck and head throughout this procedure. This portion of the 
study will be videotaped (Figure 2B and D).  
Safety: Since the most important safety concern with rTMS is the possibility of seizure, participants with active 
seizure disorder or those at increased risk of seizure will be excluded. Low frequency protocols carry less risk 
of seizure as compared to high frequency protocols given that high frequency generates cortical excitability.32 
In spite of the theoretically increased risk of seizure in accelerated rTMS protocols, several accelerated high-
frequency protocols have been safely performed in other patient populations and have been tolerated well by 
patients without evidence of increased adverse events.22-24 The majority of these accelerated protocols are 
high-frequency stimulation, whereas our protocol calls for low-frequency stimulation which actually has an 
inhibitory effect and may actually be protective against seizures. A fuller review of accelerated rTMS protocols 
in a variety of different patient populations, with all adverse events listed can be found in the supplementary file 
included with this submission- it should be noted that the seizure risk was not greater in accelerated rTMS 
protocols compared to standard rTMS protocols. Other mild and transient side effects that participants may 
experience secondary to TMS include transient eye pain, toothache, muscle twitch, facial pain, neck stiffness, 
and pain or discomfort at the application site and skin.  
 
Depression measure and suicide risk: If the Beck Depression Inventory reveals that the patient has feelings 
of harming themselves (Question 9 score 2 or above), we will refer them to mental health services available at 
Shands at the University of Florida. 
 
Clinical Assessments: 
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): This is an objective scale evaluating 
patients on a variety of features including maximal excursion, duration, effects of sensory trick, shoulder 
elevation, range of motion, and time. This portion of the study will be videotaped.  
Beck Depression Inventory (BDI): This is a 21-question survey evaluating depression in patients on a 0 to 3 
scale.  
Trail-Making Test: This is a 2-part evaluation in which patients are instructed to connect circles in ascending 
numerical order and are scored on how quickly they are able to complete the task.  
Wisconsin Card Sorting Test (WCST): This is a cognitive task that asks patients to sort cards based on color, 
number, and shape.  
Gait Assessment: Patients will be asked to walk across the Zeno walkways system for temporal parameters 
(stance time, double support time, stride time, and cadence), spatial parameters (stride length, step width, step 
length, step asymmetry), and the dynamic stability index (ratio between single and double support time). This 
portion of the study will be videotaped.  
 
Patient will also have HD-EEG and TMS measures (MEP, CSP, and SICI) performed as described above. 
 
Patients will have primary and secondary outcome measures performed at six timepoints: Baseline (T0), 
following rTMS (T1), and 2 weeks following rTMS (T2) during session 1 (S1) and baseline (T0), following rTMS 
(T1), and 2 weeks following rTMS (T2) during session 2 (S2) (Figure 1). The study protocol will take place over 
approximately 24 weeks. All events related to the study procedure will take place within +/- 14 days of the 
expected timeline, with more details below (Table 1).  
 
 
Table 1. Timeline of study events and expected study activities at each timepoint.  
 
 

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Session 
S1 
S2 
Study 
Events (to 
occur +/- 14 
days) 
Screen-
ing 
Botox- 
Week 0 
Baseline 
(T0)- 
Week 9 
rTMS 
protocol 
(4 days) 
Post-
TMS 
(T1)- 
Week 10 
2 weeks 
post-
TMS 
(T2)- 
Week 12 
Botox- 
Week 12 
Baseline 
(T0)- 
Week 21 
rTMS 
protocol 
(4 days) 
Post-
TMS 
(T1)- 
Week 22 
2 weeks 
Post-
TMS 
(T2)- 
Week 24 
Informed 
Consent 
 
 
 
 
 
 
 
 
 
 
 
Medical 
History 
 
 
 
 
 
 
 
 
 
 
 
Neurologic 
Exam 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy 
Test (if 
woman of 
childbearing 
age) 
 
 
 
 
 
 
 
 
 
 
 
Demographic
s 
 
 
 
 
 
 
 
 
 
 
 
Botox 
 
 
 
 
 
 
 
 
 
 
 
Active or 
Sham rTMS 
 
 
 
 
 
 
 
 
 
 
 
TWSTRS 
 
 
 
 
 
 
 
 
 
 
 
BDI 
 
 
 
 
 
 
 
 
 
 
 
Trail Making 
Test 
 
 
 
 
 
 
 
 
 
 
 
WCST 
 
 
 
 
 
 
 
 
 
 
 
MEP 
 
 
 
 
 
 
 
 
 
 
 
CSP 
 
 
 
 
 
 
 
 
 
 
 
SICI 
 
 
 
 
 
 
 
 
 
 
 
Gait 
assessment 
 
 
 
 
 
 
 
 
 
 
 
HD-EEG 
 
 
 
 
 
 
 
 
 
 
 
Study 
Compensatio
n 
 
 
 
 
 
 
 
 
 
 
 
 
Compensation: Participants who live a minimum of 50 miles from Gainesville will be offered a 4-night hotel 
stay of up to $100 per night in Gainesville (for 4 nights) so that they can complete the 5 consecutive days at 
the S1:T1 and S2:T1 timepoints. That way they can complete this portion of the study without having to travel 
back to their home each night. This will be paid in the form of gift cards at the time the patient and family are 
staying at the hotel ($400 for the S1 time period and $400 for the S2 time period). In addition, participants will 
be compensated up to $300 ($150 for gas and $150 for food) during their visits to the Fixel Center/UF related 
to participation in this study. This will be prorated so that they will receive $50 in gift cards ($25 for gas and $25 
for food) in 6 equal installments at each of the outcome measure timepoints: S1:T0, S1:T1, S1:T2, S2:T0, 
S2:T1, and S2:T2. Participants will also be compensated $150 for taking part in the study (for their time). This 
compensation will be prorated, so that patients will receive $25 in gift cards in 6 equal installments, correlating 
with the S1:T0, S1:T1, S1:T2, S2:T0, S2:T1, and S2:T2 outcome timepoints.  
  
Data Safety Monitoring Plan: The research team monitors the patient safety and data collection of each 
study visit.  The Data Safety and Monitoring Committee will meet once each year to review the recruitment, 
adverse events, data collection, and other aspects of the study.  The Data Safety and Monitoring Committee 
will be notified of any adverse events that occur during the course of the study, within 2 business days of the 

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specific adverse event.  This will allow the DSMC to review any issues that arise in a timely manner.  Breaches 
of confidentiality will also be monitored by the DSMC.  If there is possible harm to subject safety or the 
possibility of, any harm due to something new that was learned during the study, the DSMC will be 
convened.  If there is possible harm to subject safety or the possibility of, any harm due to something new that 
was learned during the study, the DSMC will be convened. In addition, the DSMC will meet after the first two 
patients in the study have completed the protocol to ensure safety and tolerability parameters are being met. 
Coralie de Hemptinne, PhD, Ashley Rawls MD, and Aparna Wagle Shukla MD will monitor the safety of the 
project yearly. Dr. Rawls will serve as an independent health professional on the Data Safety Monitoring 
Committee.  
Location: The clinical portions of the study will be performed at the Fixel Neurological Institute; patients will 
have the clinical outcome measures collected in a clinic or research room. Patients will have the clinical 
outcome measures collected in a clinic or research room. The NeuroStar TMS machine is located in a 
separate TMS room within the Fixel Neurologic Institute. The Zeno gait walkway system is also located in the 
Fixel Neurologic Institute. Other devices necessary to complete the study inclue these portable devices which 
will reside in the TMS room during the study procedure:  
EMG system: Bagnoli™ Desktop EMG system (Delsys, Inc., Boston, Massachusetts). It includes four surface 
electrodes to detect muscle movement  
EEG system: ActiveTwo system (Biosemi, Amsterdam, Netherlands). It has a cap with electrodes in a 
preconfigured montage, using 128 Ag-AgCl electrodes. 
 
Possible Discomforts and Risks: There are some possible discomforts and risks for participants taking part in 
this study, most of which are mild or transiently related to the study protocol and will abate afterwards. 
TMS: 
• 
Headaches – Headaches and neck aches can occur. They can be related to stabilizing the neck when 
measuring TMS. They are usually short lasting and respond easily to over the counter analgesics. 
• 
Transient hearing threshold shift – There is a possibility of temporary mild hearing loss due to the noise of the 
TMS machine. The rate of this risk is unknown yet. Earplugs will be provided to the participant to reduce the 
potential for this risk.   
• 
Seizure – A theoretical risk associated with brain stimulation. Since FDA clearance of TMS, the seizure risk is 
≤0.1% per patient (less than 1 in 1000 patients).  In the event that the participant has a seizure, the study 
staff will immediately stop the treatment session and make sure that the participant is safe during the seizure.  
The participant will be watched for a period of time after the seizure to make sure he or she is feeling well. 
Individuals with an active seizure disorder are excluded. 
• 
Fainting – Not directly related to magnetic stimulation. It is thought to be related to anxiety and psycho-
physical discomfort during the procedure. The laboratory is equipped, and staff is trained to respond to this 
risk if fainting occurs. However, the participant will be at very low risk (less than 1%) for fainting. Transfer to 
the emergency room might be needed if the participant fails to improve as expected. 
• 
Effect of Magnetic Stimulation – The NeuroStar TMS Therapy System is contraindicated for use in patients 
who have conductive, ferromagnetic, or other magnetic-sensitive metals implanted in their head within 30 
cm of the treatment coil. Examples include cochlear implants, implanted electrodes/stimulators, aneurysm 
clips or coils, stents, bullet fragments, jewelry and hair barrettes. Failure to follow this restriction could 
result in serious injury or death. The NeuroStar TMS Therapy System is contraindicated for use in patients 
who have active or inactive implants (including device leads), including deep brain stimulators, cochlear 
implants, and vagus nerve stimulators. Contraindicated use could result in serious injury or death. To avoid 
these complications, participants with any of the above listed implanted objects will be excluded from this 

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study.Childbearing Potential- There may be unknown risks to the fetus. Therefore, women of childbearing 
age will complete a pregnancy test for the TMS portion of the study at each visit. In order for the women of 
childbearing age to participate in this study, the participant should avoid becoming pregnant from their first 
day of most recent menses.  A negative pregnancy test does not absolutely prove that a woman is not 
pregnant.  If the female participant thinks that there is a possibility that she might be pregnant, the study team 
should be notified immediately. Nursing mothers are not eligible for participation in this project.  The 
possibility exists that complications and undesirable side effects, which are unknown at this time, could occur.   
EEG: 
• 
A gel paste is used to attach the sensors during EEG which may mildly and briefly irritate the skin on the 
scalp or face. Hair products cannot be used on the day of testing (or should be washed out prior to testing), 
which may be inconvenient to the participant. 
 
Possible Benefits: The participant may or may not benefit from taking part in the study. All participants will 
continue receiving botulinum toxin injections every 12 weeks as part of their standard of care. All patients will 
receive both active and sham rTMS; since the active rTMS is hypothesized to augment the effects of botulinum 
toxin injections, patients may experience further reduction in symptoms or sustained response to botulinum toxin. 
The information gathered from this study will benefit the neurology department and the larger research 
community as we continue to seek the most efficacious treatments for cervical dystonia.  
Regulatory Approval and Statistics: The study will be approved by the University of Florida Institutional Review 
Board, and all subjects will provide written informed consent. The study is highly feasible given the relatively 
large number of patients with cervical dystonia that receive botulinum toxin injections on a regular basis.  This is 
a pilot study so it has not been powered for statistical significance. We will use descriptive statistics and ANOVA 
to run analysis on the data that has been collected.  
Confidentiality: Information collected about the patient will be stored in locked filing cabinets or in computers 
with security passwords.  Only certain people have the legal right to review these research records, and they will 
protect the secrecy (confidentiality) of these records as much as the law allows. These people include the 
researchers for this study, certain University of Florida officials, the hospital or clinic (if any) involved in this 
research, and the Institutional Review Board (IRB; an IRB is a group of people who are responsible for looking 
after the rights and welfare of people taking part in research). Otherwise the research records will not be 
released without participant permission unless required by law or a court order. 
 
Researchers will take appropriate steps to protect any information they collect about participants. However, 
there is a slight risk that information about participants could be revealed inappropriately or accidentally.  
Depending on the nature of the information such a release could upset or embarrass them, or possibly even 
affect their insurability or employability.   
 
If the results of this research are published or presented at scientific meetings, patient identity will not be 
disclosed. 
 
 
 
 
 
 
 
 
 
 

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