A Non-Invasive Neuromodulation Device for Treatment of Migraine Headache
Phase: NA
Conditions: Migraine Headache, Episodic
Sponsor: Scion NeuroStim

1 
 
Version 072414 Schulman Version 4 
 


		


	
 
Title: A Non-Invasive Neuromodulation Device for Treatment 
of Migraine Headache 
Background  
 
This “Pivotal Study” is a multi-center, triple-blinded, placebo-controlled, randomized 
Pivotal Study for adjunctive prophylactic treatment of episodic migraine headache using 
a caloric vestibular stimulation (CVS) Device developed by Scion NeuroStim, LLC 
(SNS).  This Study has been reviewed by the FDA and is classified as NSR (non-
significant risk). 
 
Set forth at the end of this document is an alphabetical listing of the various capitalized 
definitions and terms that are used throughout the document, and attached are various 
forms that will be used to conduct and collect data during the Pivotal Study. 
  
Efficacy of neuromodulation therapy for migraines is reasonably well-established.  
Traditionally, however, neuromodulation, especially when accomplished through an 
expensive, surgically implanted device, has been available only as a treatment of last 
resort -- to be used (and covered by health insurance) if, but only after, patients have 
failed all other interventions, principally pharmaceuticals.  Typically, patients receive 
neuromodulation for migraines only after they are refractory or close to being refractory.  
SNS envisions changing that paradigm, providing effective early interventions and 
thereby improving outcomes for migraine patients.  The CVS-M Device is non-invasive 
and utilizes the same underlying mode of neural modulation (activation of the vestibular 
nuclei in the brainstem) that for a century has been well-understood by the medical 
profession and has been used safely via caloric irrigators for diagnostic purposes -- in 
ENT practices to assess balance and in the ER to assess brain function.   The SNS Device 
is relatively inexpensive and easy to operate; it can be used safely at home by a patient 
under the supervision of a prescribing physician.   Through availability and use of the 
SNS CVS-M Device, prophylactic neuromodulation therapy for migraines can become an 
inexpensive and early, rather than an expensive and belated, therapeutic option.  
 
Experience with pilot study patients as well as a theoretical understanding of CVS 
indicates that the SNS Device likely can effectively treat both episodic and chronic 
migraine patients, but this Pivotal Study will focus on only episodic patients.  The 
Investigators at the Pivotal Study sites will identify, select and treat a carefully defined 
population of individuals who are current patients with an established history of episodic 
migraines and who have substantial monthly migraine days and pain, but who have not 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B2 of 139

2 
 
Version 072414 Schulman Version 4 
 
yet become refractory to all conventional treatments.  CVS-M Device treatments will be 
evaluated as a therapy to be used alongside the therapies that are currently being utilized 
by participating patients (i.e., as an adjuvant), again underscoring the potential 
advantages of earlier neuromodulation therapy intervention. Limiting participation to 
patients who meet the carefully selected qualifications will simplify how the Pivotal 
Study is conducted and how the results are evaluated.  
 
All participants will be patients whose response to prior therapies has been partially 
successful, but limited, and whose disease state and current course represent risk for 
eventual refractoriness but who have not yet become fully refractory.  As defined in 
detail below, under International Headache Society (IHS) guidelines all of these patients 
will be classified as “episodic” or acute.  None will be classified as “chronic.”  In 
assessing the effectiveness of the SNS CVS-M Device, the Pivotal Study will consider 
both (1) a patient’s number of Headaches as well as (2) the severity of each and of all of 
those Headaches.  The current design path involves evaluating those two disease factors 
both separately and on a blended basis. The primary endpoint is based on a traditional 
measure with which both the FDA and the medical profession are quite familiar:   
outcomes data collected during the Treatment Period vs. baseline data from the Pre-
Treatment Baseline Period, focusing on comparative number of Migraine Headache 
Days. Additionally, the concept of blending those two disease measures into one 
quantitative assessment will be introduced:  a Total Monthly Headache Pain score.  As 
defined below, that Monthly measure will be the cumulative maximal Headache Pain 
Scores for all Headache Days (days on which the patient’s Headache Pain level is one or 
higher on an eleven-point scale) during the Month in question – thus, a quantitative 
indication of Total Monthly Headache Pain.  Study data can (and will) also be analyzed 
using other metrics, as described below. 
 
For the Pivotal Study to demonstrate efficacy from SNS CVS-M Device treatments, the 
therapy must provide prophylactic and/or abortive-response benefits for patients.  
(However, for clarity, CVS-M is viewed as providing adjunctive prophylactic therapy.) 
Experience from IRB-approved pilot studies indicates that beneficial preventive effects 
and diminished incidence and severity of Headaches are achieved through daily CVS-M 
treatments, but not necessarily beginning immediately upon the first treatment.  For that 
reason, patients will be treated for three Months and only the Headache burden during the 
last Month will be used for comparison with baseline data. 
 
Description of the Treatment Paradigm and Study 
 
1)  Intended Use/Indication for Use 
 
• Intended Use: The SNS CVS-M Device is intended to stimulate the vestibular 
system via external ear canals using controlled thermal waveforms.  
• Indication for Use: The SNS CVS-M Device is specifically indicated to treat 
episodic Migraine Headache pain. 
 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B3 of 139

3 
 
Version 072414 Schulman Version 4 
 
2)  Patient Selection Criteria Pre-Treatment Data   
In 
working 
with 
and 
through 
their 
respective 
designated 
Pivotal 
Study 
assistant(s)/coordinator(s), the Investigators will identify and screen potential 
participants, all of whom will have previously been diagnosed as episodic migraine 
patients. The Investigators will review the patients' medical records to select those 
individuals whom they identify as meeting the inclusion criteria for participating in the 
Study.  
• Inclusion Criteria: Each participant must have a Pre-Treatment History that, 
when initially screened by a Pivotal Study Investigator or designee, documents 
that she/he meets all elements of the following:   
o The patient must have been diagnosed with episodic Migraine Headache at 
least six months prior to entering into the Study, consistent with the 
International Headache Classification of Headache Disorders-II (ICHD-II) 
guidelines. 
o The patient must have a history of at least three consecutive months of 
stable Migraine Headaches prior to entering the Study.  The patients will 
not have had changes in medication usage for the three Months leading up 
to the Study, nor will they introduce new medications during the Study 
period. Patients will satisfy these criteria: On a Monthly basis, at least 
four, and not more than a total of fourteen (4-14), Headache Days  of 
which between four and fourteen (4-14) are Migraine Headache Days.  
o The patient must not have failed on more than two classes of properly 
administered 
prophylactic 
pharmaceutical 
therapies 
for 
migraine 
headache.  The patient may be on a single migraine prophylactic as long as 
the dosage has not been altered within three months of starting the Study 
and the dosage must not be altered for the duration of the Study; 
o The Investigator must have confidence in the patient's ability to reliably 
use the CVS-M Device and promptly complete the Daily Headache Diary 
forms and promptly return them to the Study coordinator.  That Daily 
Headache Diary will be completed from the beginning of the Pre-
Treatment Baseline Period through the end of the Pivotal Study. It is 
described more fully below and in the Definitions section at the end of this 
document. 
 
• Exclusion Criteria: Individuals who:  
o are pregnant  
o have a history of cardiovascular disease  
o work night shifts 
o have been diagnosed with vestibular migraine  
o have been diagnosed with migraine with aura  
o have menstrual migraine exclusively  
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B4 of 139

4 
 
Version 072414 Schulman Version 4 
 
o have been diagnosed with post-traumatic migraine   
o have a history of unstable mood disorder or unstable anxiety disorder  
o use a hearing aid 
o have a cochlear implant 
o have chronic tinnitus 
o have temporomandibular joint disease 
o have been diagnosed with traumatic brain injury 
o have been diagnosed with neurological disease other than Headaches 
o have a diagnosed vestibular dysfunction  
o abuse alcohol or other drugs 
o are experiencing medication overuse Headaches (individuals with respect 
to whom the Investigator is concerned that analgesic abuse is involved 
based on the ICHD-II guidelines).  
o are less than 18 years old or greater than 65 years old 
o have had eye surgery within the previous three months or ear surgery 
within the previous six months   
o have active ear infections or a perforated tympanic membrane 
o have participated in another clinical trial within the last 30 days or are 
currently enrolled in another clinical trial   
o are using Botox treatments for migraines. 
o Though not excluded, patients taking anti-histamines or anti-nausea drugs 
will be encouraged not to take such medications within four hours prior to 
a CVS-M treatment.  The Investigator should review other medications 
taken by the patient with properties that mimic anti-nausea or anti-
dizziness drugs as these may reduce responsiveness of the vestibular 
system to caloric stimulation.  Such medications should also be avoided 
within four hours prior to a CVS-M treatment. 
   
• Withdrawal Criteria 
o Subjects must be withdrawn from the clinical trial if any of the following 
events occur: 
 A subject does not continue to meet Inclusion/Exclusion criteria. 
 A subject is significantly non-compliant with the requirements of 
the protocol (Investigator decision). 
 A subject becomes pregnant during the trial as evidenced by a 
positive pregnancy test. 
 The subject develops an illness (Adverse Event) that would 
interfere with his/her continued participation. 
 The subject is unwilling to continue due to lack of efficacy. 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B5 of 139

5 
 
Version 072414 Schulman Version 4 
 
 The subject withdraws his/her consent. 
 The Investigator feels that it is the subject's best interest to be 
withdrawn. 
 Scion Neurostim discontinues the study or has achieved the 
targeted enrollment.   
 
If the subject is discontinued from the participation in the study for any 
reason, the Investigator must make every effort to perform all evaluations 
for the final visit and document the reasons for discontinuation.  
 
• Concomitant Medications 
o The use of acute abortive medications for the symptomatic treatment of 
migraine headache will be allowed during the clinical trial. Subjects may 
use their usual acute abortive medications, and medications should not be 
changed during the clinical trial.  A Treated Headache will be a Migraine 
Headache for which a patient has taken an acute abortive medication. 
o The patient may be on a single migraine prophylactic as long as the 
dosage has not been altered within three months of starting the Study and 
the dosage must not be altered for the duration of the Study.  The patient 
must not have failed on more than two classes of properly administered 
prophylactic pharmaceutical therapies for migraine headache. Prophylactic 
medications used to treat other medical conditions may be used, at the 
Investigator's discretion, if the subject is taking a stable dose for at least 
three months prior to screening and continues throughout the study. 
 
3)  Pivotal Study Size; Randomization 
The design size contemplates enrolling up to eighty (80) patients who will successfully 
follow through to completion of their participation in the Pivotal Study.  Half of these 
patients will be assigned a Treatment Device, and half will be assigned a Placebo Device.  
Whether a patient is in the treatment arm or placebo arm will be decided randomly based 
on an assignment within a sealed envelope, which will be opened only by the Pivotal 
Study coordinator at the relevant Pivotal Study site.  The envelopes will be randomized 
as described below and provided to the participating clinics.  A given patient and the 
Investigator will remain blinded as to the arm to which the patient has been assigned. The 
assessment of the primary endpoints will be completed by a blinded, central Statistician. 
The patients will be told, within the informed consent document, of the existence of a 
placebo arm. 
Block randomization with a block size of four (4) will be used at each site.  Each site will 
receive sets of well-shuffled envelopes in packets of four.  A given packet will be 
completed before the next packet is opened.  Each packet of four will contain two cards 
specifying that a subject should be in the active treatment arm and two cards specifying 
the placebo arm.  This procedure results in six possible different arrangements, for four 
patients, of the ordering of treatment and placebo assignments. The unblinded Pivotal 
Study coordinator will record the patient’s designation but will not share the assignment 
with the patient, Investigator, or Statistician. 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B6 of 139

6 
 
Version 072414 Schulman Version 4 
 
4)  Pivotal Study Schedule; Subject Enrollment and Activities; Monitoring 
The Pivotal Study Period will last one hundred and twelve days, beginning with a Pre-
Treatment Baseline Period of one Month (28 days), at the end of which the Investigator 
will reconfirm the appropriateness of the subject’s participation in the Pivotal Study, 
followed by a Treatment Period of three Months (84 days). 
As noted, subjects will be advised that during the Pivotal Study Period they may maintain 
patterns of usage of approved therapeutic medications that they normally use and that 
they should not initiate new medications, medicating patterns or other interventions. 
Accommodations for rescue medications will be made, using pharmaceuticals from an 
approved list developed by the Investigators. 
Potential participants will be required to keep a Daily Headache Diary throughout the 
Pivotal Study Period and, inter alia, to document times of CVS-M treatments.  They will 
enter the Daily Headache Diary information using a computer-based system.   
The phases and activities of the Pivotal Study are listed below: 
(i) 
Screening & Baseline Period: Once the subject has been established as 
having the appropriate Pre-Treatment History, she/he will be asked to 
complete a review of the informed consent.  If the subject agrees to participate 
in the Pivotal Study, the subject will then complete a Screening Visit. If the 
subject is recommended for continuation in the Study after the Screening Visit 
and tentatively approved by an Investigator, she/he will start a Daily Headache 
Diary and continue to make entries for twenty-eight consecutive days. The 
Pivotal Study coordinator will complete a Headache History Questionnaire for 
the subject. The subject will undergo a Vestibular Testing Procedure to 
establish a baseline record.  Any abnormality identified during the Vestibular 
Testing Procedure for a potential subject will be reported both to the relevant 
Investigator and to the Vestibular System Coordinator, either of whom can 
disqualify such potential subject from participating in the Pivotal Study. 
 
(ii) 
Clinic Period: After enrollment, the completion of one Month of Daily 
Headache Diary entries, and reconfirmation by the relevant Investigator of the 
subject’s participation in the Pivotal Study, the subject will come to the clinic 
for appointments for two days (within the same week) for treatments and for 
training with respect to use of the CVS-M Device. During the first clinic visit, 
the subject will complete a Quality of Life and Cognition Assessment exam.  
Also, women of childbearing age will complete a urine-based pregnancy test to 
reconfirm that they are not pregnant.  The local Pivotal Study coordinator will 
open, at random, an envelope assigning the patient to the treatment arm or the 
placebo arm.  The second clinic day may be skipped if the Study Coordinator 
feels that the patient is prepared to use the CVS-M device properly (this should 
be confirmed with a phone call on the second day). The clinic period is 
described below. 
 
On each visit during the clinic period, the subject will receive a treatment and 
be instructed in how to self-administer a defined, controlled treatment using 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B7 of 139

7 
 
Version 072414 Schulman Version 4 
 
the CVS-M Device.  During the first visit, the patient will complete a training 
session based on a set training module.  The patient will complete a 
proficiency evaluation and the Pivotal Study coordinator will certify the 
patient’s proficiency in the use of the CVS-M Device.  Blood pressure will be 
monitored every five minutes until the treatment is completed. The Pivotal 
Study coordinator will complete a Visit Assessment form each day. During the 
first clinic visit, the “2-week” visit and the final visit, the relevant Pivotal 
Study coordinator will collect treatment delivery data from the CVS-M 
Device.  The treatment delivery data from the CVS-M Device consists of 
temperature waveform files that contain actual measured temperature values 
that were delivered to the earpieces during treatments.  This data will be 
plotted in graphical form and the Pivotal Study coordinator will place the 
temperature data in the patient records.  This data is an independent record of 
the expected Device performance and is used for confirmation purposes only.  
The data files also record treatment times and patient compliance will be 
verified based on those time records.  At the end of training, a first Usability 
questionnaire will be completed by the patient. 
 
For clarity, the treatment schedule is: 
• Days 1 & 2: Completion of a set training module.  A single 
treatment administered by the Pivotal Study coordinator with the 
subject following the treatment procedure closely.  Both before 
and after the treatment the Pivotal Study coordinator will describe 
and demonstrate to the patient how a treatment procedure is 
initiated and successfully completed.  At the end of the session 
the Pivotal Study coordinator will ask the patient to proceed as if 
she or he were providing a treatment to herself or himself, and the 
Pivotal Study coordinator will observe, monitor and instruct as 
advisable.  If the Study Coordinator believes that the patient does 
not need a second day of training, a phone call interview can be 
conducted instead (in that case, the usability questionnaire should 
be completed on Day 1). If a second treatment day is used, a 
single treatment at the clinic administered by the subject with the 
Pivotal Study coordinator overseeing the treatment procedure 
closely and assessing the competence of the patient to self-treat is 
recommended. If the Pivotal Study coordinator concludes that the 
subject is ready, the subject will then be allowed to continue 
twice-daily treatments at home until the end of the Treatment 
Period.  The patient will be instructed that if she or he has any 
questions or encounters any issues at home, the patient should 
immediately call the Pivotal Study coordinator. If the Pivotal 
Study coordinator concludes that the patient is not ready for self-
treating at home and that additional training is needed, the patient 
will be instructed to return to the clinic the next day to receive 
such additional training.  A usability questionnaire will be 
completed. 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B8 of 139

8 
 
Version 072414 Schulman Version 4 
 
• Day 3-4: repeat the schema specified for Day 2 only if the subject 
needs additional training time. 
 
(iii) 
Treatment Period: The eighty-four days (3 Months) following the Pre-
treatment Baseline Period constitute the Treatment Period.  This is the test 
period, the results from which will be measured against the Pre-Treatment 
Baseline Period data.  Specifically, data from the last Month of the Treatment 
Period will be compared with the Monthly data from the one-month-long Pre-
treatment Baseline Period. Roughly two weeks after the start of treatment, a 
Pivotal Study clinical visit will occur and another Visit Assessment form will 
be completed, treatment delivery data from the CVS-M Device will be 
collected, and a Quality of Life and Cognition Assessment exam will be 
performed.  A Vestibular Testing Procedure will be completed.  A second 
usability questionnaire will be completed.  The patient will be asked to bring 
the CVS-M Device to the clinic to perform a treatment in front of the Pivotal 
Study coordinator to reaffirm proficiency in using the Device.  Any issues 
related to balance or other safety concerns will promptly be referred to both the 
relevant Investigator and the Vestibular System Consultant, either of whom 
can terminate the patient’s further participation in the Pivotal Study if 
necessary. 
 
(iv) 
Return of CVS-M Device & clinic visit: At the end of the Treatment Period 
the patient will be asked to return the CVS-M Device and a Quality of Life and 
Cognition Assessment exam will be performed. A Vestibular Testing 
Procedure will be completed.  A third usability questionnaire will be 
completed.  All remaining treatment delivery data from the CVS-M Device 
will be collected.  
 
(v) 
During each of the clinic visits, the relevant Pivotal Study coordinator will 
interview the subject, collect treatment delivery data from the CVS-M Device 
according to the schedule above and complete assessment forms. Collectively, 
data from the Daily Headache Diary, Quality of Life and Cognition 
Assessment and Visit Assessments will ensure assessment of safety and also 
coverage of all six core areas of assessment highlighted by Turk et al.:  (1) 
pain; (2) physical functioning; (3) emotional functioning; (4) global ratings of 
satisfaction; (5) any negative health states and/or adverse events; and (6) 
subject disposition.  Additionally, Visit Assessments and usability 
questionnaire forms will provide information to SNS with respect to 
satisfaction with the comfort, fit, operation, etc. of the CVS-M Device.  At all 
times throughout the Study Period all subjects will have access to an 
Investigator or her/his designated Study coordinator by telephone, email and/or 
visit.  
 
 
 
 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B9 of 139

9 
 
Version 072414 Schulman Version 4 
 
5)  Active Treatment Parameters; Placebo Treatments 
 
The following parameters will be set for active treatments using the CVS-M Device: 
• A standardized CVS time-varying waveform lasting approximately 19 minutes 
will be used for all active treatment patients at all Pivotal Study sites.  
Treatments will be administered twice daily.  The two daily treatments will be 
separated by at least one hour. 
• The waveform schedule for active treatment patients will consist of a warm 
sawtooth delivered to one ear and a cold sawtooth delivered to the other ear.  
The warm sawtooth will go from body temperature to 42 °C, and the cold 
sawtooth will go from body temperature to 17 °C.  The two waveforms will be 
delivered simultaneously, but will have different oscillation frequencies.  After 
each two-day period, the warm and cold waveforms will be switched so that 
the opposite ears will be treated with the different caloric stimulation.  Thus 
every two days the ear receiving the cold stimulus will be switched to the 
warm stimulus and vice versa. 
 
The following parameters will be set for the placebo treatments using the CVS-M 
Device: 
 
• A standardized CVS time-varying waveform lasting approximately 4 minutes 
will be used for all placebo treatment patients at all Pivotal Study sites.  
Treatments will be administered twice daily.  The two daily treatments will be 
separated by at least one hour. 
• The waveform schedule for placebo treatment patients will consist of turning 
on the cooling fans and leaving the earpieces unpowered for a ~4-minute 
period. 
• The earpiece tips will be covered with EVA rubber to prevent cooling of the 
ear canal by the metallic earpieces. 
 
The Placebo Device will look identical to the Treatment Device and will show, on its 
screen, a time-varying waveform similar to that for an active treatment.  The y-axis of the 
plot will be labeled “stimulation intensity” and will not list temperature values (the same 
will be true for the Treatment Device).  A patient receiving a placebo treatment will have 
the sensation of the earpieces creating some pressure in the ear canals and may feel the 
earpieces warm up to body temperature. Placebo patients will not undergo material 
caloric vestibular stimulation since no temperature gradient will be created across the 
horizontal semicircular canal. (The threshold for therapeutic benefit using CVS has not 
been established, but even small temperature changes can result in nystagmus 
(Sedjawidata et al. & Vesterhauge et al.).)  The term “CVS” will not be used in 
describing the Device to any patient and no reference to caloric stimulation will be made.  
The Device will be referred to as a neuromodulation device and the specific mechanism 
of action will not be disclosed to patients. 
 
All patients will be told that they may or may not benefit from the Device in terms of 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B10 of 139

10 
 
Version 072414 Schulman Version 4 
 
pain reduction and that, further, the point in the 3-month treatment period at which a 
change may be noticed is unknown and may vary from patient-to-patient – i.e., the 
treatment duration necessary for a potential reduction in pain is unknown for any 
particular individual.  Patients will be told that they may or may not sense slight pressure 
from the earpieces, a warming or cooling sensation, or slight nausea or dizziness, 
especially at the end of the treatment session.  At the conclusion of the Treatment Period, 
patients will be asked to identify which arm they believe they entered (active treatment or 
placebo). 
 
6)  Safety; Vestibular System Examination and Monitoring 
CVS has been used extensively and safely in the practice of medicine since its discovery 
more than a century ago by Dr. Robert Barany, a discovery for which he received the 
Nobel Prize in Physiology/Medicine in 1914.  There have been no reports in the literature 
of adverse events or significant negative side effects associated with CVS.  The side 
effect profile from use of the CVS-M Device is expected to be the same as that associated 
with diagnostic CVS procedures. 
CVS-M acts on the central nervous system via the vestibular organs.  This mechanism is 
distinctly different from most forms of neurostimulation that involve either electrical 
currents applied directly to a target nerve or region (implanted neurostimulators) or a 
diffuse current to larger areas of the cortex (TMS, CES, tDCS).  CVS is non-invasive and 
easily employed.  The SNS CVS-M Device enables its therapeutic use and utility by 
controlling thermal induction and providing safeguards that ensure treatments remain 
firmly within parameters established by the supervising physician. 
The Berg Balance test (Berg et al.) is well-established and widely used in clinical settings 
to asses a person’s static and dynamic balance abilities.  Inter alia, the Test is used to 
quantify clinical improvement or deterioration in patients -- from evaluation of “normals” 
to assessment of individuals with a wide range of balance impediments.  The long form 
Test consists of 14 balance- related tasks ranging from standing up from a sitting position 
to standing on one foot.  Each task is graded from 0 – 4, and the final measure is the sum 
from all elements of the Test: 
 
• 41-56 = low risk of fall 
• 21-40 = medium risk of fall 
• 0–20 = high risk of fall 
 
The Berg Balance test will provide a consistent and easily administered, task-based 
scheme for identification and quantification of deterioration, if any, of a subject’s balance 
that could be associated with use of the CVS-M Device.  The local clinical coordinators 
will undergo training on administration of the Berg test prior to the Study.  Abnormal 
findings with the Berg test may lead to a more extensive vestibular assessment 
evaluation. No unexpected side effects, nor any adverse events, have occurred in prior 
studies utilizing the CVS-M Device. 
   
 
7) Pivotal Study Endpoints 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B11 of 139

11 
 
Version 072414 Schulman Version 4 
 
 
• Primary Efficacy Endpoint for the Pivotal Study   
For active-treatment subjects as a group: During the third Month of the 
Treatment Period, their average total number of Monthly Migraine Headache 
Days will be lower than their comparable averages derived from the Pre-
Treatment Baseline Period. 
• Secondary Efficacy Endpoints for the Pivotal Study  
o The number of active-treatment subjects having a reduction of 50% or 
more in Migraine Headache Days during the third Month of the 
Treatment Period as compared with the Pre-Treatment Baseline Period 
will exceed the number of placebo-treatment patients having that 
response rate. 
o For active-treatment subjects as a group: During the third Month of the 
Treatment Period, their average Total Monthly Headache Pain Scores 
will be lower than their comparable averages derived from the Pre-
Treatment Baseline Period. 
o For active-treatment subjects as a group: During the third Month of the 
Treatment Period, their average number of Treated Headaches will be 
lower than their comparable averages derived from the Pre-Treatment 
Baseline Period. 
o For active-treatment subjects as a group: On average, in comparison 
with their Pre-Treatment Baseline Period, they will have at the end of 
the Treatment Period, improvement in scores associated with the 
Quality of Life and Cognition Assessment measures. 
• Safety Endpoint for the Pivotal Study: 
The principal safety endpoint for the Study is to verify the absence of material 
dizziness, with the associated risk of falls, as a consequence of using the 
active-treatment Device.  The Berg Balance test will be used to assess any 
changes in balance performance as a result of Device usage.  Transient nausea 
and minor dizziness may be experienced by patients, as is sometimes reported 
in the diagnostic CVS literature, and patients will be trained to verify balance 
stability after a treatment and before standing up.  Previous pilot studies using 
the Device did not identify nausea or dizziness as side effects attributable to 
the Device, based on patient self-reporting. 
 
8)  Calculating Total Monthly Headache Pain Scores   
For each subject the following Total Monthly Headache Pain calculations will be made: 
a. Using the Daily Headache Diary data from the Pre-Treatment Baseline Period, the 
cumulative Pain Scores for all of the days on which the subject had a Headache 
during the Month will be calculated; and 
b. For the third Month of the Treatment Period, the cumulative Pain Scores for all of 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B12 of 139

12 
 
Version 072414 Schulman Version 4 
 
the days on which the subject had a Headache during the Month will be 
calculated.   
At the conclusion of the Pivotal Study, Total Monthly Headache Pain score comparisons 
will be made for each subject: Pre-Treatment Baseline Period vs. the third Month of the 
Treatment Period.  Additionally, such Total Monthly Headache Pain scores for the active-
treatment subjects as a group will be compared with those for the placebo-treatment 
subjects as a group. 
 
 
9)  Statistical Analysis and Pivotal Study Size 
 
As noted above, an experienced, independent and blinded Statistician will be utilized to 
analyze and summarize the Daily Headache Diaries for all patients.  Also, as noted, a 
blinded Neuropsychologist will analyze and summarize the Quality of Life and Cognition 
Assessment data, and a Vestibular System Consultant will perform a blinded analysis and 
summary of the data from the Vestibular Testing Procedures. 
 
Summary of the analytical methodology to be used for the Primary Endpoints  
 
• No prospective stratification: Based on the inclusion and exclusion criteria, 
there is no medical reason to stratify the Pivotal Study’s episodic migraine 
population. 
 
• Statistical method:  The Pearson’s chi-square test will be used to evaluate the 
null hypothesis, which is that “There is no difference between the number of 
Migraine Headache Days (during the third Month of the Treatment Period as 
compared with the Month during the Pre-Treatment Baseline Period) when 
comparing subjects treated with the Treatment Device and subjects treated with 
Placebo Device.”  
 
The corresponding alternative hypothesis is that: “There is a reduction in 
Migraine Headache Days (during the third Month of the Treatment Period as 
compared with the Month during the pre-Treatment Baseline Period) when 
comparing subjects treated with the Treatment Device and subjects treated with 
Placebo Device.”  
 
We seek to power the Study so as to reject the null hypothesis and accept the 
corresponding alternative hypothesis.  The following power calculations are based 
on probabilities from binomial distributions (2-sided test): 
• Assumed efficacy metric (response rate): a reduction of 50% or more in 
Migraine Headache Days with respect to baseline. 
• Assumed range of efficacy measured in the placebo arm: 10-15% 
• Assumed range of efficacy measured in the treatment arm: 45-55% 
 
 
 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B13 of 139

13 
 
Version 072414 Schulman Version 4 
 
Treatment efficacy 
Placebo efficacy 
Statistical power 
Total 
minimum 
cohort size 
45% 
15% 
80% 
72 
50% 
15% 
80% 
54 
55% 
15% 
80% 
44 
45% 
10% 
80% 
50 
50% 
10% 
80% 
40 
55% 
10% 
80% 
32 
 
The ONSTIM (occipital nerve stimulator) study (Saper et al.) recorded a placebo 
(preset stimulation) efficacy of 6% and a responder rate (reduction of 50% or 
more in headache frequency) of 39%.  Results from the PREMICE study (Cefaly, 
supraorbital transcutaneous neurostimulation) cited by Lambert listed a placebo 
efficacy of 12.1% and a responder rate of 37%.  Both studies evaluated between 
60-70 patients. Therefore, the range of 10-15% for placebo efficacy is felt to be 
relatively conservative as compared with other recent studies involving 
neuromodulation devices addressing Migraine Headache.  The assumed efficacy 
rate range for the CVS Device is based on non-statistically significant 
observations in the two previous Migraine pilot studies.  We therefore conclude 
that a total Study size of 80 patients is likely to be sufficient for the most probable 
outcomes, as that number exceeds the minimum in the table above for the most 
likely treatment and placebo efficacy cases.  For comparison, Topiramate 
(Topamax) used as a prophylactic migraine treatment reports responder rates in 
the 37-54% range and a placebo response in the low 20% range.  Therefore CVS-
M responder rates in the 45-55% range would be clinically meaningful.  
 
• Cohort size:  Each of the sites will enroll subjects with an overall goal of 80 
patients. Once up to 80 subjects have completed the Pivotal Study successfully, 
enrollment in the Pivotal Study will be stopped (at least temporarily) and the data 
will be analyzed and summarized.  Using expected levels of efficacy for the 
Treatment and Placebo Devices, this cohort size will likely be more than adequate 
to demonstrate statistical significance and reject the null hypothesis.  The cohort 
size is also expected to be adequate to establish the low rate of unanticipated 
adverse events associated with usage of the Device.  The Sponsor may choose to 
extend the Study, with IRB approval, should it be necessary to increase the patient 
cohort size. 
 
 
Summary of analytical methodologies to be used for additional safety assessments 
and for the Secondary Endpoints: 
 
• Impact with respect to usage of abortive pain medications and co-morbid 
conditions such as nausea, dizziness, photophobia and phonophobia will be 
assessed based on the subjects’ Daily Headache Diary entries and the Visit 
Assessments performed by the Investigators and their designates.  An assessment 
will be made by the blinded Statistician as to whether there is evidence of acute or 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B14 of 139

14 
 
Version 072414 Schulman Version 4 
 
sustained alterations in the listed measures and co-morbidities during the 
Treatment Period as separately compared with the Pre-Treatment Baseline Period. 
• Data collected from the Quality of Life and Cognition Assessment questionnaires 
will be utilized for two purposes.  Scoring and analysis will be performed by a 
single, highly experienced, blinded Neuropsychologist.  Analysis first will involve 
review for safety, with protocols being reviewed for changes from baseline on the 
order of one standard deviation or greater on cognitive measures (using published 
data) and declines indicating clinical change on affective measures. Triggering 
during this review will prompt a broader review for consideration of withdrawal 
due to negative effects. Analysis will then secondarily involve pilot comparisons 
between Treatment and Placebo groups with respect to changes in scores across 
measures. While the present Study is not powered for detection of treatment 
effects on cognitive/affective measures, the acquired data can serve as pilot work 
to identify promising areas for future research. 
• The following null hypothesis and alternative hypothesis will be evaluated for the 
Total Monthly Headache Pain secondary endpoint: 
o  “There is no difference between the Total Monthly Headache Pain scores 
(during the third Month of the Treatment Period as compared with the 
Month during the Pre-Treatment Baseline Period) when comparing 
subjects treated with the Treatment Device and subjects treated with 
Placebo Device.” 
o “There is a reduction in Total Monthly Pain scores (during the third Month 
of the Treatment Period as compared with the Month during the Pre-
Treatment Baseline Period) when comparing subjects treated with the 
Treatment Device and subjects treated with Placebo Device.”   
 
10)  Quality Assurance Monitor   
An independent quality assurance monitor will be used to audit Pivotal Study Sites. 
 
11)  References:  
ICDH-2: (2004). "The International Classification of Headache Disorders: 2nd edition." 
Cephalalgia 24 Suppl 1: 9-160. 
 
Berg, K. O., S. Wood-Dauphinee, et al. (1989). "Measuring balance in the elderly: 
preliminary development of an instrument." Physiotherapy Canada 41(6): 304-311. 
 
Lambert, P. (2012). "Headaches and migraines: the contribution of neurostimulation." 
Tempo Medical(April): 1-4. 
 
Saper, J. R., D. W. Dodick, et al. (2011). "Occipital nerve stimulation for the treatment of 
intractable chronic migraine headache: ONSTIM feasibility study." Cephalalgia 31(3): 
271-285. 
 
Sedjawidada, R., D. Mangape, et al. (1995). "Minimum amount of calories needed to 
elicit the vestibulo-ocular reflex in normal human subjects." Acta Otolaryngol Suppl 519: 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B15 of 139

15 
 
Version 072414 Schulman Version 4 
 
17-20. 
 
Tfelt-Hansen, P., J. Pascual, et al. (2012). "Guidelines for controlled trials of drugs in 
migraine: third edition. A guide for investigators." Cephalalgia 32(1): 6-38. 
 
Turk, D. C., R. H. Dworkin, et al. (2006). "Developing patient-reported outcome 
measures for pain clinical trials: IMMPACT recommendations." Pain 125(3): 208-215. 
 
Vesterhauge, S., S. Holm-Jensen, et al. (1984). "Caloric testing with small temperature 
gradients. Caloric zero." ORL J Otorhinolaryngol Relat Spec 46(2): 105-110. 
 
12)  Test procedures, frequency and potential actions  
Test 
Test frequency 
Actions taken in case of a suspected 
adverse outcome 
Blood pressure monitoring 
At baseline, then during 
visits in the clinic period; 
measured every five 
minutes. 
A 20% change in either direction of 
diastolic or systolic BP shall constitute 
an adverse event. Treatment will be 
aborted and subject’s BP will be 
monitored until recovery.  
 
Quality of Life and Cognition 
Assessment  
During Treatment Day 1 
(in clinic), during the 
during the “2-week” visit 
and at the conclusion of 
the Study  
 
If the consulting Neuropsychologist 
concludes that the subject is exhibiting 
significant changes from baseline, the 
subject will be withdrawn from the 
treatment phase of the Pivotal Study and 
assessed again 3 months later. 
Vestibular Testing Procedure 
All patients will undergo 
testing at the start of the 
Pre-Treatment Baseline 
Period, during the “2-
week” visit and at the 
conclusion of the Pivotal 
Study.  The Berg Balance 
test long form will be used.  
If the subject is found to have a 
significant vestibular abnormality not 
detected or disclosed in the baseline 
history, prior to the start of the treatment 
phase he/she will be withdrawn from 
participation.  If the subject is found to 
have a change with respect to the 
baseline exam, upon completion of the 
Pivotal Study appropriate mitigating 
actions will be taken and the patient will 
be assessed again after 3 months. 

 

DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B16 of 139

16 
 
Version 072414 Schulman Version 4 
 

• Generally, International Headache Society (IHS) definitions, 
including the definition of Migraine Headache and episodic 
Migraine Headache, will be used in planning and conducting the 
Study.  The summary in Tfelt-Hansen et al. for prophylactic 
migraine studies serves as the principal reference. 
• CVS means caloric vestibular stimulation. 
• CVS-M shall mean using CVS therapy for migraine headaches. 
• Daily Headache Diary shall mean recordings of relevant Headache 
and other Pivotal Study information by each subject on a daily basis 
using the computer-based entry system.  Each subject will be 
instructed to complete the Daily Headache Diary report between six 
p.m. and midnight each day during the Study Period.  The Daily 
Headache Diary will ask the subject to record, for that day, what 
her/his maximum Headache Pain Score has been and the times at 
which she/he administered the treatments.  The Daily Headache 
Diary will be the principal instrument for assessing the Primary 
Endpoints and Secondary Endpoints, and the Diary data will be 
analyzed by a qualified, blinded clinical studies Statistician.  
• Enrollment Re-Confirmation Period shall be a few days (as few as 
reasonably practicable) immediately following the end of the Pre-
Treatment Baseline Period, during which time the relevant 
Investigator will evaluate a potential Pivotal Study participant’s data 
from the Pre-Treatment Baseline Period, assess all other factors and 
determine whether the individual should be enrolled and scheduled 
to begin treatments. 
• Headache shall mean a pain located within the subject’s head when 
the subject assigns to it a Pain Score between one and ten on the 
Headache Pain Scale. 
• Headache Day shall mean a day during which the subject has a 
Headache. 
• Headache-Free Day shall mean a day on which the subject does not 
have a Headache – that is, a day when the subject has a Headache 
Pain Score of zero. 
• Headache History Questionnaire shall mean a listing of patient 
history elements relevant to the assessment of her or his migraine 
headache status. 
• Headache Pain Scale shall mean an eleven-point pain measurement 
scale from zero (no pain) to ten (most intense pain).  The pain data 
will also be mapped onto a four-point (0 – 3) scale and to a 
description based on “mild/moderate/severe” categories to facilitate 
placing this Pivotal Study in the context of other prophylactic pain 
studies. Patients will be trained on the scale shown below in order to 
rank their pain on the 11-point scale: 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B17 of 139

17
Version 072414 Schulman Version 4
 
Pain scores will be summarized on a 4-point scale as well (0-3) 
where the transformation shall be achieved in accord with the graph 
below: 
 
• Investigators will include:   
o Daniel Laskowitz, MD, Ph.D., Duke U. Medical Center, 
Dept. of Medicine-Neurology, Durham, NC 
o Dianne Scott, MD, Duke U. Medical Center, Dept. of 
Anesthesiology-Pain Division, Durham, NC 
o Michael Hoffer, MD, Naval Medical Center San Diego, 
Dept. of Otolaryngology, San Diego, CA 
o Dr. Mohamed Sakel, FRCP, East Kent University Foundation 
Hospital Trust, Director/Consultant Physician of East Kent 
Neurorehab Unit, Kent, UK 
o David Wilkinson, Ph.D., Dept. of Psychology, University of 
Kent, UK 
o Joel Saper, MD, Michigan Headache and Neurology 
Institute, Ann Arbor, MI 
o Anne Calhoun, MD, Carolina Headache Institute, Chapel 
Hill, NC 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B18 of 139

18 
 
Version 072414 Schulman Version 4 
 
o Marshall Freeman, MD, Headache Wellness Center, 
Greensboro, NC 
 
• Migraine Headache In terms of diagnosis shall mean (following the 
ICDH-II guidelines) a Headache that lasts at least four hours, reaches 
a Pain Score of at least four on the Headache Pain Scale (moderate 
or severe), is not attributed to another disorder and has at least two of 
the following characteristics from A and at least one of the 
characteristics from B, respectively: 
o A:  (1) unilateral location; (2) pulsating quality; (3) moderate 
or severe pain intensity; (4) aggravation by or causing 
avoidance of routine physical activity (e.g., walking or 
climbing stairs); 
o B: During Headache: (1) nausea and/or vomiting; (2) 
photophobia and phonophobia;  
 
For the purpose of the Study, headaches will be classified using the 
patient’s own judgment.  Patients will receive instructions on how to 
differentiate a migraine headache from a non-migrainous headache.  
Treated Headaches will be considered to be Migraine Headaches.  
 
• Migraine Headache Day shall mean any calendar day during which 
a patient had a Migraine Headache of at least 30-minutes in duration.  
• Month or Monthly shall mean or refer to a period of twenty-eight 
days, usually consecutive in timing. 
• Neuropsychologist will be Deborah Attix, Ph.D., Duke U. Medical 
Center, Depts. of Medical Psychology and Medicine-Neurology, 
Durham, NC. 
• Pain Score shall mean a maximal pain rating made by a subject for 
an individual Headache or for a Headache-Free Day based on using 
the Headache Pain Scale (zero to ten).   
• Pivotal Study shall mean this SNS-sponsored, multi-site, 
randomized, triple-blinded, placebo-controlled, episodic migraine 
clinical study.  
• Pivotal Study Period shall mean, with respect to each Pivotal Study 
participant, a period of 112 days beginning with the first day of the 
subject’s Pre-Treatment Baseline Period and ending when she/he 
completes making recordings in her/his Daily Headache Diary at the 
end of the Treatment Diary Period (excluding the Enrollment Re-
Confirmation Period and any gaps due to clinic scheduling issues).  
In outline, the Study Period will chronologically consist of the 
following: 
o Days 1-28 – Pre-Treatment Baseline Period. 
o Whatever few days are required for the Enrollment Re-
Confirmation Period (it may be possible to complete this 
enrollment re-evaluation on the first day during the clinic 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B19 of 139

19 
 
Version 072414 Schulman Version 4 
 
treatment week).  Any time gap here is ignored in terms of 
listing the timeframe for the Pivotal Study. 
o One to four days during which the patient comes to the clinic 
for treatments. 
o Days 29 through 112  – Treatment Period (includes days of 
treatment in the clinic).   
 
• Pivotal Study Sites will be the Duke University Medical Center, the 
Naval Medical Center at San Diego, East Kent University Hospital 
& University of Kent in England, Michigan Headache and 
Neurological Institute, Carolina Headache Institute, and Headache 
Wellness Center. 
• Placebo Device shall mean the SNS CVS-M Device wherein the 
earpieces are maintained at body temperature, thus eliminating any 
therapeutically meaningful CVS effect from operation of the Device. 
• Pre-Treatment Baseline Period shall mean, with respect to each 
Pivotal Study participant, the first month (i.e., twenty-eight days) of 
the Pivotal Study Period for such patient. 
• Pre-Treatment History shall mean, with respect to each Pivotal 
Study participant, the established migraine headache history of that 
participant. 
• Quality of Life and Cognition Assessment will consist of: 
o General mood and cognition: the Beck Depression 
Inventory® (BDI-II), Beck Anxiety Inventory® (BAI), 
Everyday Cognition 20 (Ecog20-PT), Digit-Symbol Subtest 
of the WAIS-III, Trail Making, and Controlled Oral Word 
Association (COWA).  These tests will be administered at 
three time points during the Study. 
o Long & short-term memory: an old/new paradigm for face 
recognition administered during the start of the Treatment 
Period and again after the Treatment Period. 
o The test administration and scoring will be overseen by a 
qualified Neuropsychologist who is blinded as to the identity 
of each patient. 
• Screening Visit – Once a candidate patient has signed the informed 
consent document at her/his clinical site, a screening procedure will 
be implemented.  The screening exams will include a Vestibular 
Testing Procedure. 
• SNS means Scion NeuroStim, LLC, the Pivotal Study sponsor. 
• Statistician will be Maragatha Kuchibhatla, Ph.D, Duke University 
School of Medicine, Associate Professor of Biostatistics and 
Bioinformatics, Associate Professor of Psychiatry and Behavorial 
Sciences. Dr. Kuchibhatla will compile and analyze data from all 
sites in creating a summary report. 
• Total Monthly Headache Pain shall mean, for a subject for any 
relevant monthly period, the cumulative daily Pain Scores for all 
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B20 of 139

20 
 
Version 072414 Schulman Version 4 
 
days on which the subject has a headache during such month.  An 
example, with analysis, for a hypothetical month (twenty-eight days) 
is provided as follows: 
Number of Days 
 
   Pain Score on Those Days 
18 
 
 
 
 
0 
0 
 
 
 
 
1 
1 
 
 
 
 
2 
1 
 
 
 
 
3 
 
2 
 
 
 
 
4 
1 
 
 
 
 
5 
0 
 
 
 
 
6 
2 
 
 
 
 
7 
1 
 
 
 
 
8 
2 
 
 
 
 
9 
0 
 
 
 
 
10 
The subject’s Total Monthly Headache Pain for this hypothetical 
month would be fifty-eight, calculated as follows:  nothing for the 
eighteen Headache-Free Days when the subject’s Pain Score was 
zero; then, summing 0x1 plus 1x2 plus 1x3 plus 2x4 plus 1x5 plus 
0x6 plus 2x7 plus 1x8 plus 2x9 plus 0x10 = 58.  During the month 
the subject had ten Headache Days – i.e., ten days on which the 
subject had a Pain Score of one or greater – of which eight were 
Migraine Headaches Days (Pain Score of four or greater).  Thus, the 
patient qualifies to participate in the Study, providing she/he meets 
all other qualifications.  (See inclusion criteria discussion.)    
• Treated Headache: A Migraine Headache lasting at least 30 
minutes for which a patient takes an acute abortive medication. 
• Treatment Device shall mean a SNS CVS-M Device that is fully 
active and functioning. 
• Treatment Period shall mean, with respect to each Pivotal Study 
participant, the three months following the end of the pre-Treatment 
Baseline Period.  The third Month of the Treatment Period shall be 
the primary period for which efficacy of the SNS CVS-M Device 
treatments shall be evaluated. 
• Vestibular System Consultant will be Carey Balaban, Ph.D., U. of 
Pittsburgh Medical Center, Dept. of Otolaryngology, Pittsburgh, PA. 
• Vestibular Testing Procedure shall consist of the administration of 
the Berg Balance test. The test results will be reviewed by the 
Vestibular System Consultant (who will remain blinded).   
DE NOVO REQUEST: TNM™ Device 3.2
APPENDIX B: Clinical Testing (SNS-MIG-01)
APPLICANT: Scion NeuroStim, LLC | Confidential
Page B21 of 139