A Pilot Study of the Safety of a Novel Helmet Design in Patients With Seizures
Phase: NA
Conditions: Drug Resistant Epilepsy, Drop Seizures, Generalized Tonic Clonic Seizure, Complex Partial Seizure, Fall Due to Seizure
Sponsor: Michael A. Gelfand, MD, PhD

Inflatable Helmet for Seizures 
 
Version 5 
  
 
A PILOT STUDY OF A NOVEL HELMET DESIGN IN PATIENTS 
WITH SEIZURES 
 
 
Sponsor & Principal 
Investigator 
Michael Gelfand, MD PhD 
Department of Neurology  
University of Pennsylvania 
3400 Spruce Street, 3 W Gates 
Philadelphia, PA 19104 
215-662-7227 
Michael.Gelfand@uphs.upenn.edu 
 
Sub-Investigator 
 
David Coughlin, MD 
Department of Neurology  
University of Pennsylvania 
3400 Spruce Street, 3 W Gates 
Philadelphia, PA 19104 
David.Coughlin@uphs.upenn.edu 
 
 
Study Contacts 
 
Ashlie Jefferson 
Ashlie.Jefferson@uphs.upenn.edu  
Meryl Lozano 
Meryl.Lozano@uphs.upenn.edu  
215-662-7227 
Investigational Product: 
Hövding Inflatable Helmet  
 
IRB Number: 
 
824620 
IDE Number: 
N/A 
ClinicalTrials.gov Number       NCT03443388 
 
 
 
Initial version 1:  
 
23 June 2016  
Amended Version 2 
   
30 January 2018 
Amended Version 3 
   
20 March 2018 
Amended Version 4 
   
12 June 2018 
Amended Version 5 
 
08 October 2018 
 

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Table of Contents 
 
TABLE OF CONTENTS ............................................................................................................................... 2 
STUDY SUMMARY ...................................................................................................................................... 5 
BACKGROUND AND STUDY RATIONALE ................................................................................................ 7 
1 
INTRODUCTION .................................................................................................................................. 7 
1.1 
BACKGROUND AND RELEVANT LITERATURE ..................................................................................... 7 
1.2 
NAME AND DESCRIPTION OF THE INVESTIGATIONAL PRODUCT .......................................................... 7 
1.1.1 
Nonclinical Data....................................................................................................................... 8 
1.1.2 
Clinical Data to Date ................................................................................................................ 8 
2 
STUDY OBJECTIVES ......................................................................................................................... 8 
2.1 
PART 1 OBJECTIVES ....................................................................................................................... 8 
2.1.1 
PRIMARY OBJECTIVE ...................................................................................................................... 8 
2.2 
PART 2 OBJECTIVES ....................................................................................................................... 9 
2.2.1 
PRIMARY OBJECTIVE ...................................................................................................................... 9 
2.2.2 
SECONDARY OBJECTIVE ................................................................................................................. 9 
3 
INVESTIGATIONAL PLAN .................................................................................................................. 9 
3.1 
GENERAL DESIGN .......................................................................................................................... 9 
3.1.1 
Part 1: Helmet Deployment in Controls ................................................................................... 9 
3.1.1.1 
Screening Phase ................................................................................................................. 9 
3.1.1.2 
Study Intervention Phase .................................................................................................... 9 
3.1.2 
Part 2: Helmet Deployment During Seizures ........................................................................ 10 
3.1.2.1 
Visit 1: Screening Phase ................................................................................................... 10 
3.1.2.2 
Study Intervention Phase .................................................................................................. 10 
3.1.2.3 
Visit 2 ................................................................................................................................ 10 
3.1.2.4 
Visit 3 ................................................................................................................................ 11 
3.2 
STUDY ENDPOINTS....................................................................................................................... 11 
3.2.1 
Part 1 Endpoints .................................................................................................................... 11 
3.2.1.1 
Primary Study Endpoints .................................................................................................. 11 
3.2.2 
Part 2 Endpoints .................................................................................................................... 11 
3.2.2.1 
Primary Study Endpoints .................................................................................................. 11 
3.2.2.2 
Secondary Study Endpoints .............................................................................................. 11 
4 
STUDY POPULATION AND DURATION OF PARTICIPATION ...................................................... 12 
4.1 
PART 1 ........................................................................................................................................ 12 
4.1.1 
INCLUSION CRITERIA .................................................................................................................... 12 
4.1.2 
EXCLUSION CRITERIA ................................................................................................................... 12 
4.2 
PART 2 ........................................................................................................................................ 12 
4.2.1 
INCLUSION CRITERIA .................................................................................................................... 12 
4.2.2 
EXCLUSION CRITERIA ................................................................................................................... 12 
4.3 
SUBJECT RECRUITMENT ............................................................................................................... 12 
4.3.1 
PART 1 ........................................................................................................................................ 12 
4.3.2 
PART 2 ........................................................................................................................................ 12 
4.4 
DURATION OF STUDY PARTICIPATION ............................................................................................ 13 
4.5 
TOTAL NUMBER OF SUBJECTS ...................................................................................................... 13 
4.5.1 
PART 1 ........................................................................................................................................ 13 
4.5.2 
PART 2 ........................................................................................................................................ 13 
4.6 
VULNERABLE POPULATIONS: ........................................................................................................ 13 
5 
STUDY INTERVENTION ................................................................................................................... 13 

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5.1 
DESCRIPTION ............................................................................................................................... 13 
5.2 
INTERVENTION REGIMEN .............................................................................................................. 13 
6 
STUDY PROCEDURES ..................................................................................................................... 14 
6.1 
PART 1 ........................................................................................................................................ 14 
Table 1: Schedule of Part 1 Study Procedures .................................................................................. 14 
6.1.1 
SCREENING/INTERVENTION........................................................................................................... 14 
6.1.1.1 
VISIT 1 .................................................................................................................................... 14 
6.2 
PART 2 ........................................................................................................................................ 14 
Table 2: Schedule of Part 2 Study Procedures .................................................................................. 14 
6.2.1 
VISIT SCHEDULE .......................................................................................................................... 15 
6.2.1.1 
VISIT 1 .................................................................................................................................... 15 
6.2.1.2 
STUDY INTERVENTION PART 1 .................................................................................................. 15 
6.2.1.3 
VISIT 2 .................................................................................................................................... 15 
6.2.1.4 
STUDY INTERVENTION PART 2 .................................................................................................. 15 
6.2.1.5 
VISIT 3 (END OF STUDY) .......................................................................................................... 15 
6.3 
SUBJECT WITHDRAWAL ................................................................................................................ 16 
6.3.1 
Data Collection and Follow-up for Withdrawn Subjects ........................................................ 16 
6.4 
EARLY TERMINATION VISITS ......................................................................................................... 16 
7 
STUDY EVALUATIONS AND MEASUREMENTS ............................................................................ 16 
7.1 
DEMOGRAPHICS/MEDICAL HISTORY .............................................................................................. 16 
7.2 
PHYSICAL AND NEUROLOGICAL EXAM ........................................................................................... 16 
7.3 
PREGNANCY TESTING .................................................................................................................. 16 
7.4 
SUBJECT TRAINING ...................................................................................................................... 16 
7.5 
SEIZURE CALENDAR ..................................................................................................................... 16 
7.6 
SEIZURE QUESTIONNAIRE ............................................................................................................. 17 
7.7 
HELMET DEPLOYMENT QUESTIONNAIRE ........................................................................................ 17 
7.8 
RIVERMEAD POST-CONCUSSIVE SCALE ........................................................................................ 17 
7.9 
INJURY-RELATED MEDICAL RECORD COLLECTION ......................................................................... 17 
7.10 
MONTHLY CONTACT ..................................................................................................................... 17 
8 
STATISTICAL PLAN ......................................................................................................................... 17 
8.1 
PART 1 ENDPOINT ........................................................................................................................ 17 
8.1.1 
Part 2 Endpoints .................................................................................................................... 17 
8.1.1.1 
Primary Study Endpoints .................................................................................................. 17 
8.1.1.2 
Secondary Study Endpoints .............................................................................................. 17 
8.2 
SAMPLE SIZE AND POWER DETERMINATION ................................................................................... 18 
8.3 
STATISTICAL METHODS ................................................................................................................ 19 
8.3.1 
Baseline Data ........................................................................................................................ 19 
8.3.2 
Efficacy Analysis.................................................................................................................... 19 
8.3.2.1 
PART 1 .................................................................................................................................... 19 
8.3.2.2 
PART 2 .................................................................................................................................... 19 
8.3.3 
Safety Analysis ...................................................................................................................... 19 
8.3.3.1 
PART 2 .................................................................................................................................... 19 
8.3.3.2 
PART 2 .................................................................................................................................... 19 
8.4 
SUBJECT POPULATION(S) FOR ANALYSIS ....................................................................................... 19 
9 
ADVERSE DEVICE EFFECTS AND ADVERSE EVENTS ............................................................... 19 
9.1 
DEFINITIONS ................................................................................................................................ 19 
9.1.1 
Adverse Device Effects ......................................................................................................... 19 
9.1.2 
UNANTICIPATED ADVERSE DEVICE EFFECTS (UADES) .................................................................... 20 
9.1.3 
Adverse Event ....................................................................................................................... 20 
9.1.4 
Serious Adverse Event .......................................................................................................... 20 
9.2 
RECORDING OF ADVERSE DEVICE EFFECTS AND ADVERSE EVENTS ............................................... 21 
9.3 
AE/ADE ASSESSMENT ................................................................................................................. 21 

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9.4 
Investigator Reporting ........................................................................................................... 22 
9.4.1 
Reporting to the FDA ............................................................................................................. 22 
9.4.2 
OTHER REPORTING TO THE PENN IRB .......................................................................................... 23 
9.4.3 
Follow-up reports ................................................................................................................... 23 
9.5 
STOPPING RULES ......................................................................................................................... 23 
10 
STUDY ADMINISTRATION, DATA HANDLING AND RECORD KEEPING .................................... 23 
10.1 
CONFIDENTIALITY ......................................................................................................................... 23 
10.2 
DATA COLLECTION AND MANAGEMENT .......................................................................................... 24 
10.3 
RECORDS RETENTION .................................................................................................................. 24 
11 
STUDY MONITORING, AUDITING, AND INSPECTING .................................................................. 24 
11.1 
STUDY MONITORING PLAN ............................................................................................................ 24 
11.2 
AUDITING AND INSPECTING ........................................................................................................... 24 
12 
ETHICAL CONSIDERATIONS .......................................................................................................... 24 
12.1 
RISKS .......................................................................................................................................... 24 
12.1.1 
PART 1 .................................................................................................................................... 24 
12.1.2 
PART 2 .................................................................................................................................... 25 
12.2 
BENEFITS .................................................................................................................................... 25 
12.2.1 
PART 1 .................................................................................................................................... 25 
12.2.2 
PART 2 .................................................................................................................................... 25 
12.3 
RISK BENEFIT ASSESSMENT ......................................................................................................... 25 
12.3.1 
PART 1 .................................................................................................................................... 25 
12.3.2 
PART 2 .................................................................................................................................... 25 
12.4 
INFORMED CONSENT PROCESS / HIPAA AUTHORIZATION .............................................................. 26 
13 
STUDY FINANCES ............................................................................................................................ 26 
13.1 
FUNDING SOURCE ........................................................................................................................ 26 
13.2 
CONFLICT OF INTEREST ................................................................................................................ 26 
13.3 
SUBJECT STIPENDS OR PAYMENTS ............................................................................................... 26 
14 
PUBLICATION PLAN ........................................................................................................................ 26 
15 
REFERENCES ................................................................................................................................... 26 
 
 
 

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Study Summary 
Title 
A Pilot Study of the Safety of a Novel Helmet Design in Patients with Seizures 
Short Title 
Inflatable Helmet for Seizures 
IRB Number 
824620 
Methodology 
Open Label Pilot Study 
Study Duration 
1 year 
Study Center(s) 
Single Center: University of Pennsylvania 
Objectives 
Part 1: 
• 
To determine reliability in helmet deployment, as evidenced by 
deployment of the helmet during 4 staged falls with normal controls or 
dummies 
Part 2: 
Primary: 
• 
To compare rates and types of head injuries and post concussive 
symptoms in seizures resulting in falls occurring while the helmet was 
worn versus seizures resulting in falls occurring while the helmet was 
not being worn. 
Secondary: 
• 
To determine helmet deployment in seizures versus helmet 
deployment in non-seizure situations. 
• 
To understand adverse events associated with helmet deployment 
during seizures and otherwise. 
• 
To compare rates and types of head injuries and post concussive 
symptoms from seizures leading to helmet deployment versus 
seizures in which the helmet did not deploy. This is contingent on 
there being episodes of helmet non-deployment. 
Number of Subjects 
Part 1:  4 
Part 2:  20 
Main Inclusion and 
Exclusion Criteria 
Part 1: Healthy controls  
Part 2:  Subjects who experience at least one seizure every 6 months who do 
not wear static solid helmets. 
Investigational 
Product  
Hövding Inflatable Helmet  

Inflatable Helmet for Seizures 
 
 
 
 
 
 
 
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Duration of 
administration (if 
applicable) 
Part 1: 1 day 
Part 2: 6 months 
Reference therapy 
Static solid helmet 
Statistical 
Methodology 
Part 1: the number of times that the helmet deploys in normal controls falling 
from standing. 
 
Part 2: We will compare the rates of injury and post concussive symptoms in 
patients wearing a helmet during a seizure leading to a fall (independent of 
whether or not the helmet deployed), compared to patients not wearing a 
helmet during a seizure leading to a fall. We will also collect the number of 
days that subjects assigned to wear the helmet wore the helmet.    
Safety Evaluations  
Medical Record Review, Rivermead Post Concussive Scale, Qualitative 
Subject Report  
Data and Safety 
Monitoring Plan  
The Sponsor-Principal Investigator will conduct a self-assessment to review 
and evaluate study data and activities. The details of monitoring are included 
in the Data and Safety Monitoring Plan. 
 
 
 

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 BACKGROUND AND STUDY RATIONALE 
This study will be conducted in full accordance all applicable University of Pennsylvania Research 
Policies and Procedures and all applicable Federal and state laws and regulations.  
1 
Introduction 
Patients with epilepsy often sustain head injuries from the falls that occur during their seizures.  While 
neurologists often advise patients with difficult to control seizures to wear helmets at all times to prevent 
injuries, patients nearly universally refuse because of social stigma and impracticality.  A new, less 
obtrusive, inflatable helmet has been designed by Hövding Inc. that may encourage increased helmet 
use; and therefore, potentially result in decreased head injuries caused by seizures.   
 
The primary goal of this study is to estimate effect size and trial outcome instruments to design a study of 
the safety of a new helmet designed by Hövding Inc. for use in patients with risk of head injury from 
seizures.  The target population with be patients with poorly controlled seizures.  Subjects will wear the 
helmet, fill out a seizure calendar and describe how the helmet reacted during a seizure and during its 
use in everyday life.  
1.1 
Background and Relevant Literature  
Epilepsy is a common chronic neurological condition defined by recurrent seizures that frequently lead to 
falls; the original description of epilepsy translated to “The Falling-Down Disease.1”  The CDC estimates 
that 2.3 million adults in the United States have Epilepsy, with 150,000 people developing the condition 
each year2,3.  The total indirect and direct cost of Epilepsy in the United States is estimated to be $15.5 
billion.  Recent studies have concluded that the rates of severe head injuries, lacerations, dislocations, 
fractures, and drowning in Epileptic patients are higher than their non-Epileptic counterparts4,5,6,7.  The 
risk is increased for children and as well as adults8,9. One study reported that injuries were reported in as 
many as 15% of epilepsy patients evaluated in an emergency room setting for a seizure10.  This 
population of patients is also specifically susceptible to head injuries during their seizures.  In a recent 
study that followed 247 Epilepsy patients over 10 years. 16% of patients had seizure related injuries, 79% 
of which were cranial soft tissue lacerations or contusions11.   However, these injuries can be severe and 
result in traumatic brain injury, skull fractures, and intracranial bleeding.  
 
Helmets are effective in reducing the injuries from serious falls and accidents.  A meta-analysis of 
motorcycle helmets, for example, suggest that they reduce head injuries 69% (OR 0.31, 95% CI 0.25 to 
0.38)12.   Moreover, improvements in motorcycle helmet design significantly different (reduced?) rates of 
facial injury and skull fractures13.  However, the same attention has not been paid to the helmets used in 
Epilepsy patients. In one study, 33 institutionalized young patients with drug resistant Epilepsy were 
provided with helmets to wear. 59 injuries were recorded during the trial, over half of which were scalp 
and facial bruising, with 48% of those required medical attention.  The helmet provided was not in use in 
41% of these injuries; and even so, there were not significant differences in rates of laceration, bruising, 
or the need to seek medical attention at the time of injury in the group wearing helmets versus the group 
who were not wearing the helmets.   This study not only demonstrates the difficulties with static helmet 
compliance even in a controlled setting but also calls into question whether or not standard static helmets 
themselves are optimized to prevent injuries during seizures.  
 
Patients with frequent or difficult to control seizures, are often recommended to wear a helmet at all 
times.  Unfortunately, this can result in significant social stigma.  The use of static helmets may be a 
reasonable goal for patients with significant cognitive disability, but is often not acceptable in cognitively 
normal patients who view them as socially unacceptable and impractical.  Consequently, they can 
accumulate seizure related head injuries and the financial costs resulting from subsequent emergency 
room visits and hospitalizations.  
1.2 
Name and Description of the Investigational Product  
In 2012, a Swedish company named Hövding began to manufacture a new type of inflatable bicycle 
helmet.  The helmet is designed as a collar with a deployable airbag that inflates when a sensor detects 

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rapid changes in acceleration.  When the rider encounters a crash, the airbag deploys and wraps the 
back and sides of the users head in inflated nylon fabric which then slowly deflates after deploying.  Its 
design is meant to be unobtrusive and fashion conscious to encourage greater compliance among the 
cyclist population; it is tested to a higher pounds per square inch standard than the current industry 
requirements for conventional bicycle helmets.  This technology could be adapted to serve as a potential 
safety device for patients with drug resistant epilepsy (DRE), and patients might use such a device 
because of its novel, less obtrusive and more fashion conscious design.  We believe that use of these 
helmets by individuals with DRE would reduce the number and severity of head injuries incurred by the 
DRE population. 
1.1.1 
Nonclinical Data 
The Hövding helmet is currently commercially marketed in Europe.  It is CE (Conformité Européenne) 
marked after undergoing an extensive process for approval by Science Partner Technical Research 
Institute of Sweden. CE marking is required for a cycle helmet to be able to be sold in Europe and 
certifies that the helmet complies with the requirements endorsed by the EU Directive for personal 
protection equipment. 
 
Complete protection in the event of an accident and functioning during normal use are basic criteria for 
CE marking.  For this helmet, “normal use” is defined as wearing the helmet correctly while cycling.  All 
types of helmets have to provide protection for the head in the form of shock absorption and force 
distribution in an accident to obtain CE marking.  The helmet must also be designed so as to cause no 
unnecessary risks, i.e. there must be no sharp edges, etc. which could injure the wearer. The 
environmental tolerance criteria for helmets dictate that they must be able to withstand moisture and work 
in heat and cold and when subjected to the sun’s ultraviolet light. 
 
As with many other new types of products launched on the market, for Hövding there was no standard for 
testing airbag cycle helmets. This meant that SP, which was commissioned to CE mark Hövding, had to 
develop a new test method in accordance with the requirements of the Personal Protective Equipment 
Directive, that was adapted for airbag cycle helmets. When the test method had been developed, it was 
accredited and approved by SWEDAC (the Swedish Board for Accreditation and Conformity 
Assessment). The test method for Hövding consists partly of tests that are the same as those for 
traditional cycle helmets, such as an impact test on a flat surface and on a curbstone, and tests relating to 
the features of an airbag helmet that are unique and that differ from those of traditional cycle helmets. For 
example, tests are performed to ensure that Hövding inflates when it should, doesn’t inflate when it 
shouldn't and the durability of the airbag fabric1. 
 
The Hövding helmet is not an approved medical device in the European Union or the United States.  
1.1.2 
Clinical Data to Date 
To date, there is no available clinical research data on the Hövding Inflatable Helmet. 
2 
Study Objectives 
The overall objective is to conduct a pilot study of the use of the Hövding helmet in patients with risk of 
head injury as a result of seizures to help plan a larger study to determine the safety and efficacy of the 
helmet for this indication.  Ultimately, we hope to demonstrate that its use decreases the rate or severity 
of head injuries due to seizures that occur from standing.  This study will help confirm the assumed safety 
of this device for use in patients with seizures, estimate the effect size, and pilot the use of novel patient-
administered outcome instruments and a previously validated post concussive syndrome scale.    
2.1 Part 1 Objectives 
2.1.1 
Primary Objective 
• Reliability in helmet deployment, as evidenced by the deployment of the helmet during 4 
staged falls with normal controls or dummies. 

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2.2 Part 2 Objectives 
2.2.1 
Primary Objective 
• To compare rates and types of head injuries and post concussive symptoms in seizures 
resulting in falls occurring while the helmet was worn versus seizures resulting in falls 
occurring while the helmet was not being worn 
2.2.2 
Secondary Objective 
3 
Investigational Plan  
3.1 General Design 
We propose to investigate the safety of the Hövding helmet device in patients with DRE.  While 
the Hövding helmet is commercially marketed in Europe, it has not been specifically used in a defined 
epilepsy population.  Our project would aim to analyze the safety of the use of the device during 5 
seizures from a standing position.   For Part 1 of this pilot study, the study team will test helmets on 4 
normal controls (or dummies) and have subjects fall directly over onto their sides on a padded floor and 
record whether or not the helmet deploys.  Assuming that the helmet deploys in at least 3/4 of the 4 falls 
in this scenario as we believe it will, we would proceed to the next phase of the trial. 
For Part 2, we propose to enroll 20 subjects from our DRE population who suffer frequent 
seizures Some patients are already identified and their seizure frequency is documented in a database 
maintained at the University of Pennsylvania.  We will also accept referrals from outside providers and 
review their records of seizure type, frequency, age, and pregnancy status to see if their patients qualify 
for the study.   
 This is a single-center, randomized, 2-way crossover study design. Using block randomization, 
enrolled participants will be assigned to first enter either the “helmet” or “no helmet” group following 
consent and confirmation that they meet all inclusion and none of the exclusion criteria.  At the time of a 
seizure that results in a fall, subjects will be asked to fill out a questionnaire to help document the 
circumstances of the seizure and if any injuries occurred.  If the patient seeks medical attention, their 
medical records will be reviewed afterwards.  If a head injury is sustained, they will be asked to fill out the 
Rivermead Post Concussive scale 48 hours after their seizure in order to quantify their head injuries.2  If 
the subject was wearing a helmet at the time of the fall and it deploys, or of the helmet deploys for any 
other reason, subject or their representatives will be asked to fill out an additional questionnaire detailing 
the circumstances of its deployment.  After the helmet deploys, we will ask subjects to return their helmets 
to the University of Pennsylvania for Sponsor assessment.  After this fall, or after any helmet deployment, 
subjects in both groups will be asked to return to the University of Pennsylvania for a study visit during 
which they will switch groups.  If a subject is enrolled for 3 months without experiencing a seizure 
resulting in fall, they will be asked to come to the University of Pennsylvania to return the helmet, if 
applicable, and they will be considered a screen fail.  
During their participation in both groups, subjects will be asked to fill out a daily seizure calendar 
to help document the frequency of seizures and seizure types.   
3.1.1 
Part 1: Helmet Deployment in Controls 
3.1.1.1 Screening Phase 
For Part 1 of this pilot study, the study team will recruit 4 normal controls (or dummies) using flyers placed 
around the University of Pennsylvania.  The study team will obtain informed consent, and review 
inclusion/exclusion criteria to confirm eligibility. 
3.1.1.2 Study Intervention Phase 
After the study team obtains informed consent and eligibility is confirmed, normal control participants 
(defined as non-pregnant participants without epilepsy or other diagnosis that may result in falls) will be 
given helmets and asked to fall straight over onto their right or left side onto a padded surface.  Falls will 
be witnessed and video recorded by the study team.   If the participant significantly attempts to break their 

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fall and the helmet does not deploy, they may be asked to fall again.  If the helmet inflates in 3 out of 4 
falls, we will proceed with Part 2.  If the helmet does not inflate in at least 3/4 falls, we will stop the study. 
 
3.1.2 
Part 2: Helmet Deployment During Seizures 
3.1.2.1 Visit 1: Screening Phase 
20 subjects with high seizure frequencies (greater than one seizure every 2 months and at least 1 seizure 
every 6 months that could result in a fall) will be recruited.  The primary method of recruiting subjects for 
this study will be reviewing the epilepsy database at the University of Pennsylvania and communicating 
with attending neurologists about whether it is appropriate to introduce the study to potential subjects.  
We will offer participation in the trial as part of their standard of care visits in the neurology office.  We 
expect that 20 subjects will be sufficient in this preliminary study to determine safety and to suggest 
efficacy.  Written consent from subject or legally authorized representative (LAR) will be obtained prior to 
any study procedures being conducted.  
At visit 1, the following procedures will be performed: 
• 
Subjects or LARs will sign Informed Consent prior to any study activities 
• 
Medical History  
• 
Demographics 
• 
Physical Exam including height, weight, and neck circumference 
• 
Urine Pregnancy Test (if female of childbearing potential) 
• 
Randomization 
• 
Dispense Helmet, if applicable 
• 
Dispense Seizure Calendar 
• 
Dispense Seizure Questionnaire 
• 
Dispense Helmet Deployment Questionnaire (if subject is assigned to wear a helmet) 
• 
Dispense Rivermead Post Concussive Scale (for patients able to complete scale) 
3.1.2.2 Study Intervention Phase  
• 
Subjects assigned to wear the helmet will be asked to wear the Hövding Helmet during their daily 
lives with the following exceptions: swimming, bathing, driving or riding in a car, participating in 
activities with frequent changes in velocity such as sports, or handling children or infants.   
• 
All 20 Subjects will complete a Seizure Calendar that will detail which how often and what type of 
seizures they are having  
• 
During the time they are assigned to the helmet group, subjects will also record the number days 
that they wear the helmet. 
• 
All 20 Subjects will complete a Seizure Questionnaire, which will be self-administered after the 
subject has a seizure to detail the circumstances of the seizure and any injuries sustained. 
• 
During the time they are assigned to the helmet group, subjects helmet will complete a Helmet 
Deployment Questionnaire, which will be self-administered after the Helmet deploys to detail the 
circumstances of its deployment 
• 
Those subjects able to do so will complete a Rivermead Post concussive scale which will be self-
administered 48 hours after their seizure if they sustain a head injury during a seizure or if the 
helmet deploys during a seizure, regardless of head injury.  
• 
The study team will make monthly contact with each subject, to ask about seizure frequency, 
helmet deployment, and any other relevant information. 
• 
If any subject seeks medical care for injuries during the trial, the study team will make every effort 
to obtain related medical records.  
• 
Subjects will be instructed to contact the study team after they experience a seizure that results in 
a fall, or after a helmet has been deployed to schedule a follow-up visit.   
3.1.2.3 Visit 2 
After a helmet has been deployed or the subject experiences a seizure that results in a fall, subjects will 
be asked to return for visit 2.  At this visit, the following study procedures will be performed: 

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• 
Medical History review 
• 
Adverse Device Events review 
• 
Helmet collection, if applicable 
• 
If a subject with a VNS experiences a helmet deployment, their VNS will be interrogated at visit 2. 
If a problem is detected, appropriate clinical care will be provided.  
• 
Dispense Helmet, if applicable 
• 
Collect Seizure Calendar  
• 
Collect Seizure Questionnaire  
• 
Collect Helmet Deployment Questionnaire (if subject was assigned to wear a helmet at visit 1) 
• 
Collect Rivermead Post Concussive Scale (for patients able to complete) 
• 
Dispense Seizure Calendar 
• 
Dispense Seizure Questionnaire 
• 
Dispense Helmet Deployment Questionnaire (if subject is assigned to wear a helmet at this visit) 
• 
Dispense Rivermead Post Concussive Scale (for patients able to complete) 
 
At the end of this visit, subjects will switch groups.  Those originally randomized to the helmet group will 
be assigned to the no helmet group, and those originally randomized to the no helmet group will be given 
helmets and assigned to the helmet group.   
3.1.2.4 Visit 3 
After a helmet has been deployed or the subject experiences a seizure that results in a fall, or at the end 
of six months of study participation, subjects will be asked to return for visit 3.  At this visit, the following 
study procedures will be performed: 
• 
Medical History review 
• 
Adverse Device Events review 
• 
Helmet collection, if applicable 
• 
Collect Seizure Calendar  
• 
Collect Seizure Questionnaire  
• 
Collect Helmet Deployment Questionnaire (if subject was assigned to wear a helmet at visit 2) 
• 
Collect Rivermead Post Concussive Scale (for patients able to complete) 
3.2 Study Endpoints  
3.2.1 
Part 1 Endpoints 
3.2.1.1 Primary Study Endpoints 
The primary endpoint will be the rate of helmet deployment during staged falls. 
3.2.2 
Part 2 Endpoints 
3.2.2.1 Primary Study Endpoints 
• 
Differences in Rivermead Post Concussive Scale, Seizure Questionnaire, injury-related medical 
records, and qualitative subject report between subjects wearing helmets during a seizure, and 
subjects not wearing helmets during a seizure.   
3.2.2.2 Secondary Study Endpoints 
• 
Rates of helmet deployment (per event) during seizures associated with falls, and rates of helmet 
deployment (per day of use) not associated with seizure. 
• 
Qualitative description of any adverse events. 
• 
Differences in Rivermead Post Concussive Scale, Seizure Questionnaire, injury-related medical 
records, and qualitative subject report between subjects following a seizure in which the helmet 
deployed, and seizures in which the helmet was either not being worn or did not deploy 

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4 
Study Population and Duration of Participation  
4.1 Part 1 
4.1.1 
Inclusion Criteria 
1. Age 18-60 at the time of enrollment. 
2. Have neck circumference between 34 and 42 cm. 
3. Can understand and provide written informed consent. 
4. Must be competent to follow all study procedures.  
5. Able to read, speak, and understand English. 
4.1.2 
Exclusion Criteria 
1. Subject is currently pregnant 
4.2 Part 2 
4.2.1 
Inclusion Criteria 
1. Have at least one seizure every 6 months that might result in a fall (e.g. Generalized Tonic 
Clonic Seizure, Atonic Seizure, and/or Complex Partial Seizure resulting in a fall). 
2. Has a seizure frequency of at least once per 2 months. 
3. Be between ages 18-65 at the time of enrollment. 
4. Have neck circumference between 34 and 45 cm 
5. Must live in a home with electrical power supply.  
6. If female and of childbearing potential, has negative pregnancy test at the beginning of the 
study and willing to use appropriate birth control for the duration of the study. 
7. Subject or LAR can understand and sign written informed consent. 
8. Subject or caregiver must be competent to follow all study procedures. 
9.  
4.2.2 
Exclusion Criteria 
1. Patient already wears a helmet for seizure safety. 
2. Subject is pregnant, planning to become pregnant during the study, or is unwilling to use an 
appropriate form of birth control during the study. 
4.3 Subject Recruitment  
4.3.1 
Part 1 
We will distribute flyers around the Hospital of the University of Pennsylvania to recruit normal 
controls. 
4.3.2 
Part 2 
Our primary method of recruiting subjects for this study will be reviewing the epilepsy 
database at the University of Pennsylvania, screening incoming clinic schedules, and referrals 
from attending neurologists.  We will offer participation in the trial in addition to subjects’ 
standard of care visits in the neurology office.  We propose to recruit 20 subjects with Drug 
Resistant Epilepsy (DRE) who suffer from at least one seizure every 6 months that could be 
expected to result in a fall.  Drug Resistant Epilepsy will be defined as subjects who have tried 
2 or more antiepileptic medications and still having a seizure.  Seizures that could be expected 
to result in a fall include generalized tonic-clonic seizures, drop seizure of any type, or a 
complex partial seizure with a fall.  Prior history of head injury was removed as a criterion as 
well.  We expect that 20 subjects will be sufficient in this preliminary study to determine safety 
and to suggest efficacy.  

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4.4 Duration of Study Participation 
For Part 1, each subject’s participation will last one day.  Participation is complete when the subject falls.  
Subjects may be asked to repeat the fall if necessary.  For Part 2, participation for enrolled subjects could 
last up to six months. 
4.5 Total Number of Subjects  
4.5.1 
Part 1 
Recruitment will end when 4 subjects are enrolled.   
4.5.2 
Part 2 
Recruitment will end when approximately 20 subjects are enrolled, in order to document at least 5 
evaluable seizures during helmet wear. 
4.6 Vulnerable Populations:  
N/A 
5 
Study Intervention  
5.1 Description 
The Hövding inflatable helmet is designed for cyclists as a collar with a deployable airbag that inflates 
when a sensor detects rapid changes in acceleration.  When the cyclist encounters a crash, the airbag 
deploys and wraps the back and sides of the user’s head in inflated nylon fabric which then slowly 
deflates after deploying.  Its design is meant to be unobtrusive and fashion conscious to encourage 
greater compliance among the cyclist population; it is tested to a higher pounds per square inch standard 
than the current industry requirements for conventional bicycle helmets in the EU.  Part 1 of this study, 
where normal controls (or dummies) are asked to fall from standing onto a padded surface while wearing 
the helmet, will address whether a fall outside of the context of cycling is sufficient for airbag deployment.  
If so, we will begin part 2 of the study.  
5.2 Intervention Regimen 
For part 2, enrolled participants will be assigned to first enter either the “helmet” or “no helmet” group 
following consent and confirmation that they meet all inclusion and none of the exclusion criteria.  They 
will remain in their assigned group until they experience helmet deployment and/or a seizure that results 
in a fall.   At this time, subjects or their caregivers will be asked to fill out a questionnaire to help 
document the circumstances of the seizure and if any injuries occurred.  If the patient seeks medical 
attention, their medical records will be reviewed afterwards.  If a head injury is sustained, those patients 
who are able will be asked to fill out the Rivermead Post Concussive scale 48 hours after their seizure in 
order to quantify their head injuries.2 If the subject was wearing the helmet and it deploys, the subject will 
be asked to fill out an additional questionnaire detailing the circumstances of its deployment.  After the 
helmet deploys, we will ask subjects to return their helmets to the University of Pennsylvania for Sponsor 
assessment.  After this fall, subjects in both groups will be asked to return to the University of 
Pennsylvania for a study visit during which they will switch groups.  If a subject is enrolled for 3 months 
without experiencing a seizure resulting in fall, they will be asked to come to the University of 
Pennsylvania to return the helmet, if applicable, and they will be considered a screen fail.  During their 
participation, subjects will be asked to fill out a daily seizure calendar to help document the frequency of 
seizures and seizure types.  We will compare circumstances, injuries, and post concussive scales in 
seizures where the helmet deploys to seizures where the helmet did not deploy. 
 
 

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6 
Study Procedures 
6.1 Part 1 
Table 1: Schedule of Part 1 Study Procedures 
 
Visit 1 
Informed Consent 
X 
Review Inclusion/Exclusion Criteria 
X 
Demographics/Medical History 
X 
Physical Examination 
X 
Pregnancy Test (if applicable) 
X 
Subject Training 
X 
Fall with helmet 
X 
Adverse Device Effect (ADE) / Unanticipated ADE/ / Unanticipated Problems Assessments 
X 
6.1.1 
Screening/Intervention 
6.1.1.1 Visit 1 
• 
Informed Consent  
• 
Review Inclusion/Exclusion 
• 
Demographics/Medical History 
• 
Physical Exam  
• 
Pregnancy Test – only applicable if subject is female and of childbearing potential 
• 
Subject training 
• 
Fall – subjects will be asked to fall on their sides onto a padded floor without breaking the fall 
with arms. If subject braces themselves and the helmet does not deploy, they may be asked 
to repeat the fall in the same controlled environment. 
6.2 Part 2 
Table 2: Schedule of Part 2 Study Procedures 
 
1 
Intervention 
2 
Intervention 
3 
Informed Consent 
X 
 
 
 
 
Review Inclusion/Exclusion Criteria 
X 
 
 
 
 
Demographics/Medical History 
X 
 
 
 
 
Physical and Neurological Examination 
X 
 
X 
 
X 
Pregnancy Test (if applicable) 
X 
Xa 
Xa 
Xa 
 
Subject Training 
X 
 
X 
 
 
Assignment to treatment group 
X 
 
X 
 
 
Dispense Helmet 
Xd 
 
Xd 
 
 
Seizure Calendar 
Xb 
X 
Xbc 
X 
Xe 
Seizure Survey 
Xb 
Xd 
Xbce 
Xd 
Xe 
Helmet Deployment Survey 
Xb 
Xd 
Xbce 
Xd 
Xe 
Rivermead Post Concussive Scale 
Xbd 
Xd 
Xbcde 
Xd 
Xed 
Monthly Contact 
 
X 
 
X 
 
Collect Helmet 
 
 
Xd 
 
Xd 
Adverse Device Effect (ADE) / Unanticipated 
ADE/ Unanticipated Problems Assessments 
 
X 
 
X 
X 
a Subsequent urine pregnancy tests may be administered at the investigator’s discretion if there is reason to believe the subject may 
be pregnant.   
b dispensing 
c collection 
d if applicable 

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6.2.1 
Visit Schedule 
6.2.1.1 Visit 1 
• 
Informed Consent  
• 
Review Inclusion/Exclusion 
• 
Demographics/Medical History 
• 
Physical and Neurological Exam  
• 
Pregnancy Test – only applicable if subject is female and of childbearing potential 
• 
Subject Training 
• 
Assignment to treatment group 
• 
Dispense Helmet (if applicable) 
• 
Dispense as applicable: Seizure Calendar, Seizure Survey, Helmet Deployment Survey, 
Rivermead Post-Concussive Scale 
6.2.1.2 Study Intervention Part 1 
• 
Seizure Calendar - daily 
• 
Seizure Questionnaire – self-administered after a seizure 
• 
Helmet Deployment Questionnaire – self-administered after helmet deployment 
• 
Rivermead Post-Concussive Scale – self-administered by appropriate patients 48 hours after a 
seizure if the subject sustains a head injury during a seizure or if the helmet deploys during a 
seizure 
• 
If subject seeks medical care for injuries during the trial, the study staff will collect any information 
available, including medical records. 
• 
Study staff will contact subjects monthly 
6.2.1.3 Visit 2  
• 
Physical and Neurological Exam  
• 
Pregnancy Test – only applicable if subject is female and of childbearing potential 
• 
Subject Training 
• 
Assignment to treatment group (switch groups) 
• 
Dispense or Collect Helmet 
• 
Collect and Dispense new as applicable: Seizure Calendar, Seizure Survey, Helmet Deployment 
Survey, Rivermead Post-Concussive Scale 
• 
Adverse Device Effects Collection 
6.2.1.4 Study Intervention Part 2 
• 
Seizure Calendar - daily 
• 
Seizure Questionnaire – self-administered after a seizure 
• 
Helmet Deployment Questionnaire – self-administered after helmet deployment 
• 
Rivermead Post-Concussive Scale – self-administered by appropriate patients48 hours after a 
seizure if the subject sustains a head injury during a seizure or if the helmet deploys during a 
seizure 
• 
If subject seeks medical care for injuries during the trial, the study staff will collect any information 
available, including medical records. 
• 
Study staff will contact subjects monthly 
6.2.1.5  Visit 3 (End of Study) 
• 
Physical and Neurological Exam  
• 
Collect Helmet (if applicable) 

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• 
Collect as applicable: Seizure Calendar, Seizure Survey, Helmet Deployment Survey, Rivermead 
Post-Concussive Scale 
• 
Adverse Device Effects Collection 
6.3 Subject Withdrawal  
Subjects may withdraw from the study at any time without impact to their care.  They may also be 
discontinued from the study at the discretion of the Investigator for lack of adherence to intervention or 
study procedures or visit schedules, ADEs, or due to a change in medical status that would make the 
subject ineligible, such as pregnancy.  The Investigator may also withdraw subjects who violate the study 
plan, or to protect the subject for reasons of safety or for administrative reasons.  It will be documented 
whether or not each subject completes the clinical study. Subjects who withdraw early will have one final 
visit to collect helmets (if applicable), calendars, and questionnaires, and to follow up regarding adverse 
events.  
6.3.1 
Data Collection and Follow-up for Withdrawn Subjects 
Subjects who withdraw consent to participate will have one final visit to collect helmet (if applicable), 
diaries, and questionnaires, and to follow up regarding adverse events.  
6.4 Early Termination Visits   
Subjects who withdraw consent to participate will have one final visit to collect helmet (if applicable), 
diaries, and questionnaires, and to follow up regarding adverse events.  
7 
Study Evaluations and Measurements  
7.1 Demographics/Medical History 
Study staff will collect baseline demographics and medical history at screening visit. A medical history will 
be reviewed and recorded at the Screening visit.  Epilepsy history including etiology, seizure type(s), 
description, duration, and resulting falls will be documented.  
7.2 Physical and Neurological Exam 
The principal investigator or designated sub-investigator (MD or NP) will perform a baseline physical and 
neurological exam and document findings in the subject’s file.  Follow up physical and neurological exams 
will be performed at visits 2 and 3.  The systems to be reviewed will be left to the Investigator’s judgment.  
7.3 Pregnancy Testing 
A urine pregnancy test will be performed for female subjects of childbearing potential.  Subsequent urine 
pregnancy tests may be administered at the investigator’s discretion if there is reason to believe the 
subject may be pregnant.  Pregnant subjects will be removed from the study. 
7.4 Subject Training 
Subjects in the helmet group will be trained on proper use of the Hövding Inflatable Helmet and will be 
provided with an information packet. Subjects or their caregivers will also be trained on the completion of 
seizure calendars and questionnaires.  
 
7.5 Seizure Calendar 
At the first screening visit, all subjects will be given copies of a seizure calendar.  On a daily basis, the 
subject or theior caregiver is to complete this calendar, which will capture self-reported (or observed by 
caregiver) seizures and helmet wearing, as well as seizure-free or helmet-free days.  At subsequent 
visits, this seizure calendar will be reviewed and collected.  A new calendar will be given at visit 2. 

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7.6 Seizure Questionnaire 
At visits 1 and 2, all subjects will be given copies of the seizure questionnaire to be filled out after the 
subject has a seizure.  This questionnaire will capture information such as whether or not the subject was 
wearing the helmet, whether or not the helmet deployed, the position the subject was in during the 
seizure, what happened during the seizure, and whether the subject was injured or needed medical 
attention. 
 
7.7 Helmet Deployment Questionnaire 
At visits 1 and 2, subjects in the helmet group will be given copies of the helmet deployment 
questionnaire to be filled out after the helmet deploys (either during a seizure or otherwise).  This 
questionnaire will capture information such as whether a seizure caused the helmet to deploy, what the 
subject was doing at the time, whether any injuries were obtained, and whether any medical care was 
needed or obtained. 
 
7.8 Rivermead Post-Concussive Scale 
At visits 1 and 2, subjects able to complete the scale will be given copies of the Rivermead Post-
Concussive Scale to be filled out at baseline and 48 hours after a seizure if the subject sustains a head 
injury during a seizure or if the helmet deploys during a seizure.  This questionnaire will capture 
information regarding cognitive, somatic, and emotional symptoms associated with post-concussion 
syndrome. 
 
7.9 Injury-Related Medical Record Collection 
If subjects seek medical care for injuries during the trial, the study staff will collect any information 
available, including medical records.  Medical records from the University of Pennsylvania will be 
collected via the electronic medical record.  The study staff will make all efforts to obtain related records 
from all other sites not affiliated with the University of Pennsylvania with the subject’s permission. 
 
7.10 
Monthly Contact 
Study staff will establish contact with subjects monthly via phone or email to ask about seizure frequency, 
falls, and time spent wearing the helmet.  Staff will document the communication in subject files.  
8 
Statistical Plan 
8.1 Part 1 Endpoint 
The primary endpoint will be the rate of helmet deployment during staged falls. 
8.1.1 
Part 2 Endpoints 
8.1.1.1 Primary Study Endpoints 
• 
Differences in Rivermead Post Concussive Scale, Seizure Questionnaire, injury-related medical 
records, and qualitative subject report between subjects wearing helmets during a seizure, and 
subjects not wearing helmets during a seizure.  
8.1.1.2 Secondary Study Endpoints 
• 
Rates of helmet deployment (per event) during seizures associated with falls, and rates of helmet 
deployment (per day of use) not associated with seizure. 
• 
Qualitative description of any adverse events. 

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• 
Differences in Rivermead Post Concussive Scale, Seizure Questionnaire, injury-related medical 
records, and qualitative subject report between subjects following a seizure in which the helmet 
deployed, and seizures in which the helmet was either not being worn or did not deploy 
8.2 Sample Size and Power Determination 
N/A 
 
 

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8.3 Statistical Methods 
 
Part 2:   
• 
Will compare rates of injury and post concussive syndrome in falls where the helmet was being 
worn versus falls where the helmet was not being worn. 
• 
Descriptive statistics will be collected on the proportion of days that subjects assigned to wear the 
helmet actually wear the helmet 
• 
Descriptive statistics will also be collected on rates of helmet deployment (per event) during 
seizures associated with falls, and rates of helmet deployment (per day of use) not associated 
with seizure 
• 
Will compare rates of injury and post concussive syndrome in falls where the helmet was being 
worn and deployed versus falls where the helmet was either not being worn or did not deploy 
8.3.1 
Baseline Data 
Baseline and demographic characteristics will be summarized by standard descriptive statistics (including 
mean and standard deviation for continuous variables such as age and standard percentages for 
categorical variables such as gender). 
8.3.2 
Efficacy Analysis  
8.3.2.1 Part 1 
• 
Number of times the helmet deploys in normal controls (or dummies) falling from a standing position. 
8.3.2.2 Part 2 
• 
Number of days that subjects in the helmet group actually wore the helmet 
• 
Compare the fraction of the time the device deployed during a seizure that resulted in a fall 
• 
Compare the number of times the helmet deployed in a seizure vs. non-seizure event 
• 
Compare seizures that trigger helmet deployment to those that do not trigger helmet deployment 
8.3.3 
Safety Analysis  
All subjects entered into the study and randomized at the baseline visit will have detailed information 
collected on adverse device effects (ADE) for the overall study safety analysis. 
8.3.3.1 Part 2 
• 
N/A 
8.3.3.2 Part 2 
• 
Compare the rates of injury and post concussive syndromes in subjects where the helmet inflated 
during a seizure related fall to seizure related falls where the helmet did not inflate. 
8.4 Subject Population(s) for Analysis 
• All-randomized population:  Any subjects in the study, regardless of whether they were assigned 
to wear the helmet, will be used for any analysis comparing helmet wear vs. no helmet wear. 
9 
Adverse Device Effects and Adverse Events 
9.1 Definitions 
9.1.1 
Adverse Device Effects 
An adverse device effect (ADE) is any untoward medical occurrence associated with the use of a device 
in humans.  

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9.1.2 
Unanticipated adverse device effects (UADEs) 
An unanticipated adverse device effect is any ADE that meets at least 1 of the following 3 criteria:  
1. Any serious adverse effect on health or safety caused by or associated with a device,  
 
In this case, serious adverse effect is defined as any ADE that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• another important medical event 
 
All ADEs that do not meet any of the criteria for serious should be regarded as non-serious ADEs.  
 
2. Not previously identified in nature, severity, or degree of incidence in the application,  
3. Any other unanticipated serious problem associated with a device that relates to the rights, safety, or 
welfare of subjects. 
9.1.3 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
9.1.4 
Serious Adverse Event 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event (SAE) is any AE that 
is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
 
9.1.5 
Expectedness 
AEs/ADEs must be assessed as to whether they were expected to occur or were unexpected, meaning 
not anticipated based on current knowledge found in the protocol or product label. 
 
Expected/Anticipated:  an AE/ADE known to be associated with the intervention or condition under 
study. 
 
Unexpected/Unanticipated:  an AE/ADE for which the nature, frequency, or severity is not consistent 
with information about the condition under study or intervention in the protocol, consent form, or product 
label. 

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9.2 Recording of Adverse Device Effects and Adverse Events 
The study investigator is ultimately responsible for the recording and reporting of AEs, ADEs, and 
unanticipated problems related to the research, which occur during the study. The study team will collect 
AE and ADE information from the start of the study (after consent is signed) until the last follow up visit.   
 
At each contact with the subject, a member of the study team will seek information on AEs and ADEs by 
specific questioning and, as appropriate, by examination.  Information on all AEs and ADEs will be 
recorded immediately in the source document.  All clearly related signs, symptoms, and abnormal 
diagnostic procedures results should be recorded in the source document, though should be grouped 
under one diagnosis.  These AEs and ADEs will be recorded on paper source documents and reviewed 
by the Principal Investigator and Sponsor designated pharmacovigilance lead (Medical Director). 
 
All AEs and ADEs occurring during the study period will be recorded.  The clinical course of each event 
will be followed until resolution, stabilization, or until it has been determined that the study intervention or 
participation is not the cause.  SAEs and UADEs that are still ongoing at the end of the study period will 
be followed up to determine the final outcome.  Any SAEs and UADEs that occur after the study period 
and is considered to be possibly related to the study intervention or study participation will be recorded 
and reported immediately. 
9.3 AE/ADE Assessment 
The Sponsor-Investigator will determine relationship classification (definitely related, probably related, 
possibly related, unlikely or unrelated), expectedness (expected or unexpected), and seriousness 
(serious or non-serious as defined per protocol) of all AEs and ADEs. The relationship of each event will 
be followed up on until it has been determined that the event is definitely related or definitely not related 
to the device or participation on the study.  
 
 

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9.4 Investigator Reporting  
9.4.1 
Reporting to the FDA 
Federal Regulation 21 CFR 812.150 dictates mandatory reporting requirements for all IDE and 
abbreviated IDE studies to the FDA and the IRB. The regulations describe both expedited and annual 
reporting requirements. Events that do not warrant expedited reporting will be reported at the time of the 
IDE Annual Report submission to the FDA. Events that require expedited reporting will be reported to the 
FDA using Form FDA3500A.  
 
Reportable Safety Events 
What Event is Reported 
To Whom is Event 
Reported 
When is Event Reported 
Possibly, Probably, or Definitely 
Related,  Unanticipated, & Fatal 
Penn IRB 
Within 3 days of initial 
receipt of information 
FDA 
Within 10 days of  initial 
receipt of information 
Possibly, Probably, or Definitely 
Related,  Unanticipated, & Serious 
(Non-Fatal) 
Penn IRB 
Within 10 days of  initial 
receipt of information 
FDA 
Possibly, Probably, or Definitely 
Related,  Unanticipated, & Non-Serious 
Penn IRB 
Within 10 days of  initial 
receipt of information 
FDA 
Annually 
Possibly, Probably, or Definitely 
Related,  Anticipated, & Serious or Non-
Serious 
Penn IRB 
At continuing review 
FDA 
Annually 
Unlikely or Definitely not related,  
Anticipated, & Serious or Non-Serious 
Penn IRB 
N/A 
FDA 
Annually 
Unlikely or Definitely not related,  
Unanticipated, & Serious or Non-Serious 
Penn IRB 
N/A 
FDA 
Annually 
 
Other Reportable Events 
What Event is Reported 
To Whom is Event 
Reported 
When is Event Reported 
Unapproved protocol deviation to assure 
protection of human subjects 
Penn IRB 
Within 5 days of  initial 
receipt of information 
FDA 
Use of device without obtaining informed 
consent 
Penn IRB 
Within 5 days of  initial 
receipt of information 
FDA 
Withdrawal of IRB approval 
FDA 
Within 5 days of  initial 
receipt of information 
Withdrawal of FDA approval 
IRB 
Within 5 days of  initial 
receipt of information 
Change in risk by IRB 
FDA 
Within 5 days of  initial 
receipt of information 
Request by the manufacturer to recall, 
repair, or dispose device 
Penn IRB 
Within 30 days of request 
FDA 

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9.4.2 
Other Reporting to the Penn IRB  
Federal Regulations 21CFR §56.108(b)(1) and 45 CFR 46.103(b)(5) require the IRB to "follow written 
procedures for ensuring prompt reporting to the IRB…any unanticipated problems involving risk to human 
subjects or others." 
 
The Office of Human Research Protections (OHRP) considers Unanticipated Problems involving risks to 
subjects or others, in general, to include any incident, experience, or outcome that meets all of the 
following criteria: 
 
• 
Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the subject population being studied; 
• 
Related or possibly related to participation in the research (in this guidance document, possibly 
related means there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research); and 
• 
Suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
 
All such reportable events will be reported to the IRB per IRB policy.  
 
Other Reportable Events to the IRB 
New information showing increased risk to subjects 
Within 10 days of  
initial receipt of 
information 
Protocol deviation that places subjects at risk or has the potential to occur again 
Any serious and continuing non-compliance 
Breach of confidentiality 
Incarceration of subject 
 
9.4.3 
Follow-up reports 
If an SAE/UADE has not resolved at the time of the initial report and new information arises that changes 
the investigator’s assessment of the event, a follow-up report including all relevant new or reassessed 
information (e.g., concomitant medication, medical history) should be submitted to the IRB and the FDA. 
The investigator is responsible for ensuring that all SAE/UADEs are followed until either resolved or 
stable. 
9.5 Stopping Rules  
In Part 1, if 3/4 of the helmets do not inflate due to a fall from standing in normal controls or dummies, the 
study will not move on to Part 2.   
10 Study Administration, Data Handling and Record Keeping 
10.1 
Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 

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permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
period. 
10.2 
Data Collection and Management  
Paper source documents created by the study team will be used to record all subject data.  This data will 
be organized and stored in patient binders located in the locked Clinical Research Office at the Penn 
Epilepsy Center, Hospital of the University of Pennsylvania, 3400 Spruce Street, 2 Silverstein, 
Philadelphia, PA 19104.  All CRFs will contain de-identified data, and all medical record printouts will de-
identified before being stored in subject binders.   
 
A password-protected excel spreadsheet that links subjects with de-identified data will be stored on the 
UPHS Neurology shared drive and will only be accessible to the appropriate study staff. 
10.3 
Records Retention  
All study records will be stored for 7 years, and every effort will be made to maintain subject 
confidentiality.  Study records and personal information may be given out if required by law.  Records will 
not be labeled with names or other identifying information.  Instead, they will be identified with a code.  
The list matching names to codes will be stored separately, password protected, and only available to 
appropriate study staff.   
11 Study Monitoring, Auditing, and Inspecting 
11.1 
Study Monitoring Plan 
The investigator will conduct a self-assessment to review and evaluate study data and activities using the 
UPenn Principal Investigator Compliance Assessment (PICA) form for IRB review at the time of 
Continuing Review. 
11.2 
Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, government 
regulatory bodies, and University compliance and quality assurance groups of all study related 
documents (e.g. source documents, regulatory documents, data collection instruments, study data etc.).  
The investigator will ensure the capability for inspections of applicable study-related facilities (e.g. clinical 
research office, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 
12 Ethical Considerations 
This study is to be conducted in accordance with applicable US government regulations and international 
standards of Good Clinical Practice, and applicable institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted Institutional Review Board 
(IRB), in agreement with local legal prescriptions, for formal approval of the study conduct.  The decision 
of the IRB concerning the conduct of the study will be made in writing to the investigator and a copy of 
this decision will be provided to the sponsor before commencement of this study.  
12.1 
Risks 
12.1.1 Part 1 
Risk may include possible injury from the fall, however, serious injury is not expected as they will be 
falling on a padded surface. Another possible risk is injury from the helmet deployment. It is possible 
that participants may have other adverse device effects that we cannot predict.   

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12.1.2 Part 2 
This study will confirm the design and operating specifications before beginning an extensive clinical 
trial.  Performance of this device in this limited study serves to establish the parameters for a larger 
clinical study. This will be the first trial of this helmet in subjects with drug resistant epilepsy and 
frequent seizures.  It is possible that subjects may have other adverse device effects that we cannot 
predict.  
 
Risks and adverse device effects that could reasonably be expected to occur include: 
• 
The helmet deploys in a situation not related to a seizure:  This risk is possible as the helmet 
has previously been designed to work in cycling.  Activities that have rapid accelerations and 
decelerations such as running, jumping, or playing sports could potentially increase the 
chances of the helmet deploying.   
• 
The helmet does not deploy during a seizure: As stated above, the helmet has not been 
previously optimized for use in this setting and, as such, may not deploy during a seizure.   
• 
Abrasions to the back of the neck when the helmet deploys 
• 
Suffocation: Considered to be very rare as when the helmet deploys, it leaves the face and 
mouth open and the helmet gradually deflates.  No reports of suffocation or near suffocation 
have been reported despite its commercial availability in Europe over the past 3 years. 
• 
Injury to those around the subject when the helmet deploys, if when deploying the subject is 
near other people 
• 
Temporary hearing impairment after helmet deployment 
• 
Discomfort from wearing the helmet collar 
 
The risk of falling is not actually an increase in risk from the usual state of participants and there is no 
increased risk of fall or injury resulting from fall with study participation. 
12.2 
Benefits 
12.2.1 Part 1 
Subjects may not receive any personal benefit from being in this study.  We hope the information 
learned in this portion of the study will provide reasonable justification for continuance of the study 
and to benefit the larger goal of adapting this technology as a safety device. 
12.2.2 Part 2 
Subjects may not receive any personal benefits from being in this study. A possible benefit is that the 
Hövding helmet may prevent a head injury during a seizure; however, the study device is 
experimental and this cannot be guaranteed. We hope the information learned from this study will 
benefit other people with similar conditions in the future. 
12.3 
Risk Benefit Assessment 
12.3.1 Part 1 
The benefits of this study outweigh the risks in that information obtained will help determine the 
appropriateness of a larger study and will contribute to the design and testing of a device that may 
help prevent head injuries in subjects with seizures.  There is only limited personal risk but also no 
personal benefit to participating in this portion of the trial. 
12.3.2 Part 2 
The benefits of this study are favorable in comparison to the risks. For those subjects who are 
assigned to wear the helmet, given that nearly no subjects wear any type of protective head 
equipment for protection because of their seizures, we believe that the use of any potentially 
protective device confers a potential benefit.  This study will not recruit subjects who already wear 
helmets. It is our hope that the risks of this study will be minimized with the close follow-up and 
communication throughout the study.  For subjects who are not assigned to wear the helmet, they will 

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have the same risks of head injury as if they were not participating in the study at all.  The benefit will 
be further validation of the study tools and a greater understanding of the risk of head injury in 
subjects with seizures. 
12.4 
Informed Consent Process / HIPAA Authorization  
At visit 1, the PI or the Study Coordinator will discuss the study with the subject. Consent for the study will 
be obtained by the PI, designee, or the sub-investigator(s).  Persons who are unable to read English are 
not allowed to consent for themselves to participate in this study. Subjects will receive an IRB-approved 
consent/HIPAA authorization form to read in person.  At the same time, the PI, designee, or Study 
Coordinator will read over the form out loud to the subject. They will be allowed as much time as they 
need to re-read the consent form. It will be stressed to the subjects that this is voluntary and in no way will 
it impact their medical care. Someone other than their direct provider will administer the consent process 
so that they will not feel any coercion. The subject will then be asked if they have any questions or 
concerns. If there are questions or concerns, these will be addressed promptly. If the subject has full 
understanding of the study description and is agreeable to the study procedures, they will be asked to 
sign the consent form. A copy of the consent form will be given to the subject. The original consent 
documents will be placed in the subject’s study binder and be securely stored at the study site. 
13 Study Finances 
13.1 
Funding Source 
This study is financed through a grant from the Epilepsy Foundation. 
13.2 
Conflict of Interest 
All University of Pennsylvania Investigators will follow the University of Pennsylvania Policy on Conflicts of 
Interest Related to Research.  
13.3 
Subject Stipends or Payments 
Subjects in Part 1 will not be compensated.  Subjects in Part 2 will be compensated $25 upon completion 
of each visit. 
14 Publication Plan 
The Principal Investigator holds the primary responsibility for publication of the results of the study.  
Approval must be first obtained from the primary responsible party before any information can be used or 
passed on to a third party.   
15 References 
1. "Hövding - Airbag for Cyclists." Hövding.com. 1 Jan. 2014. Web. 21 Aug. 2014. 
2. King NS, Crawford S, Wenden FJ, Moss NEG, Wade DT. The Rivermead Post Concussion 
Symptoms Questionnaire: A measure of symptoms commonly experienced after head injury and 
its reliability. J Neurol. 1995;242:587–592