A Phase II Prospective, Single-Arm, Open-Label, Multi-Center Study Using the Nu-V3 Cranial Nerve Stimulation Treatment Device in Patients With Chronic Pain, Anxiety, Depression, and/or Sleeplessness
Phase: NA
Conditions: Chronic Pain, Anxiety, Depression, Sleeplessness
Sponsor: Nu-Life Solutions

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A Phase I Prospective, Single-Arm, Open-Label, Multi-Center Study 
Using the Nu-V3 Cranial Nerve Stimulation Treatment Device in 
Patients with Pain, Anxiety, Depression, and/or Sleeplessness 
 
 
PROTOCOL NUMBER:  Nu-V3 PROTOCOL NO. 1  
 
INVESTIGATIONAL PHASE: Phase I 
 
VERSION: 1.2 
 
DE NOVO NUMBER:   
                              
INVESTIGATIONAL DEVICE:  Nu-V3 
 
ORIGINAL PROTOCOL ISSUE DATE:  
 
VERSION DATE:  December 14, 2017      
        
STUDY SPONSOR:  Nu-Life Solutions 
 
310 W. Michigan 
 
Indianapolis, IN 46202 
 
STUDY CONTACTS: 
Medical Monitor 
Biostatistician 
Clinical Trial Manager 
Brad Doebbeling 
Name Here 
Eric T. Siebeneck 
(317)941-6709 
Phone Here 
(317)941-6709 
bdoebbeling@nu-
lifesolutions.com 
Email Here 
esiebeneck@nu-
lifesolutions.com 
 
CONFIDENTIALITY STATEMENT 
This document is the property of Nu-Life Solutions. It contains confidential and proprietary information belonging to 
Nu-Life Solutions; therefore, its use is intended solely for physicians, clinical research staff, and contract research 
organizations (“study personnel”) participating in clinical studies of Nu-V3. Reproduction is authorized for and strictly 
limited to study personnel for Nu-Life Solutions, reproduction for any other purpose is prohibited. 
 
 
Sponsor Protocol Signature: 
 
 
 

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Protocol Signature Page 
 
A Phase I Prospective, Single-Arm, Open-Label, Multi-Center Study 
Using the Nu-V3 Cranial Nerve Stimulation Treatment Device in 
Patients with Pain, Anxiety, Depression, and/or Sleeplessness 
 
 
Protocol Amendment 1: December 14, 2017 
 
By signing below, the Investigator attests that they will adhere to the protocol and 
Informed Consent Form and report, to the Study Sponsor and the IRB, any adverse 
device or participant study event. 
 
 
 
Investigator Name:       __________________________________________________ 
 
Title:                             __________________________________________________ 
 
Address:                      __________________________________________________ 
 
Address:                      __________________________________________________ 
 
Address:                      __________________________________________________ 
 
Phone:                        __________________________________________________ 
 
Facsimile:                    __________________________________________________ 
 
Signature:                    __________________________________________________ 
 
Date:                            __________________________________________________ 
 
 
 

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1.0 Introduction 
1.1 Background 
Research evidence has shown that the symptoms of pain, anxiety, depression, and 
sleeplessness, or any combination of these symptoms are prevalent in patient 
populations with chronic medical conditions, particularly inflammatory arthritis (Psoriatic 
Arthritis, Rheumatoid Arthritis), Fibromyalgia, anxiety disorders (PTSD, Generalized 
Anxiety Disorder), Depression, Chronic Pain conditions (neuropathy, chronic neck and 
back pain, Osteoarthritis, TMJ Syndrome), and Sleep Disorders.  Patients with one of 
these chronic conditions often have clusters of one or more of these four symptoms 
(anxiety, depression, pain and sleeplessness).  
These patient populations have a need for an innovative treatment approach to 
address these symptoms, as they often occur simultaneously.  By addressing all 
possible combinations of these symptoms in an individual patient or population, 
significantly improved outcomes can be achieved.  
Globally, the lifetime prevalence of anxiety disorders from a 2013 meta-analyses was 
7.3% (4.8-10.9%) and ranged from 5.3% (3.5-8.1%) in African cultures to 10.4% (7.0-
15.5%) in Euro/Anglo cultures.1 This translates into 1 out of 13 and 1 out of 10 people 
affected globally and in North America respectively. In the United States alone, anxiety 
affects about 18% of the population or 40 million adults age 18 and older at cost of 
more than $42 billion a year in 1990.2,3 
 
In a separate systematic review on depression, the global prevalence of major 
depressive disorder: was 4.7% (4.4-5.0%).4  In 2015, over 16 million adults aged 18 or 
older have been estimated to have had at least one major depressive episode in the 
prior year representing 6.7% of all U.S. adults.5 
 
Insomnia is a global public health issue and is believed to affect approximately 30-35% 
of the global population.6,7 Poor sleep has been associated with decreased immunity, 
depression, anxiety, poorer quality of life, obesity, increased pain, occupational errors, 
absenteeism from work, and motor vehicle crashes.7,8 
 
The prevalence of chronic pain, like all the previous conditions discussed, is highly 
variable by population and other factors. It is estimated that approximately 20% of the 
adult European population has chronic pain.9 Similarly, approximately 17.6% (about 40 
million) of US adults experience severe levels of pain along with over 11.2% (25.3 
million) of adults suffering from daily pain for the prior 3 months at an annual estimated 
cost of approximately $560-$635 billion.10,11  
 
Given the high prevalence of conditions associated with pain, anxiety, depression, 
and/or sleeplessness (PADS), the associated economic burden, and lack of safe and 
cost-effective therapies, interest and research is expanding into the field of 
neuromodulation therapies, including TENS devices, to meet this need. 
 

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The Nu-V3 device is not considered to be a Transcutaneous Electrical Nerve 
Stimulation (TENS) device. TENS devices are applied only in the area of the body 
directly related to the pain. The Nu-V3 device is placed on the auricular (ear) area and 
utilizes a non-invasive electrical micro-signal to access the cranial nerves via three 
small electro-gel pads. There are no TENS devices currently approved or cleared by 
the FDA that qualify as being substantially equivalent.  
  
Under further research pertaining to accessing the cranial nerves, in particular the 
vagus nerve, we discovered that there are a variety of Vagal Nerve Stimulators 
available. However, none are non-invasive and small enough to be attached to the ear 
while stimulating multiple cranial nerves in the auricular area. 
 
In summary, while Nu-V3 is technically a transcutaneous device, the mechanism for 
mitigation of symptoms (pain, anxiety, depression and sleeplessness) is unique by 
TENS standards for the following reasons: 
 
A. TENS is typically placed in the general area where the pain exists.  Nu-V3 is 
placed only in the auricular area (on the ear) and accesses the cranial nerves as 
the mechanism for relief. 
B. TENS devices are known to stimulate muscular tissue and nerves in the area 
where pain exists, creating vasodilation (increased blood flow) and thereby the 
possibility of temporary relief. Nu-V3, by accessing the cranial nerves 
(specifically the vagus nerve) non-invasively, acts to stimulate the body’s natural 
enkephalins and elevate blood flow, and may result in the balancing or 
rebalancing of the Autonomic Nervous System (ANS).12-18   
C. By accessing the cranial nerves in the manner described above, the effect may 
be cumulative and residual and offer the patient immediate, intermediate and 
longer lasting results and relief. 
 
For the reasons cited above, Nu-Life will be submitting Nu-V3 for FDA clearance under 
De Novo 513(f)(2), as a new and unique technology.  In part, the purpose of this clinical 
study is to demonstrate the effect upon the four specific symptoms of pain, anxiety, 
depression and sleeplessness, as any one or combination of these symptoms may 
result in Autonomic Nervous System dysfunction. 
 
1.2 Device Description 
 
The Nu-V3 device is a miniaturized, wearable, microchip-controlled, cranial nerve 
stimulation treatment device, which delivers pulsed micro-signals over a period of 14 
days. The Nu-V3 device provides a continuous flow of intermittent, low frequency 
electrical pulses to the ear’s specific cranial nerve endings.  The Nu-V3 device is a 
patent pended, non-invasive transcutaneous stimulating device which offers useful 
features to the patient and clinical professional.  The Nu-V3 device control features are 
set by the manufacturer and prevent patient misuse of the device. 
Three miniature, non-invasive, electro-gel pads are utilized to deliver a micro signal at 1 

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Hz in a square plus minus waveform, which cycles on and off every three hours to 
provide a resting period and prevent adaption to the stimulation.  The device is 
powered by three (No.10) zinc air batteries at 1.4 volts each, 4.2 volts in total, to 
provide the required stimulation for up to 14 days.  The low frequency, reliability of the 
zinc air batteries and consistency of the micro-signal through the eight-pin micro-chip 
technology, provides consistent and equivalent stimulation energy regardless of 
individual skin impedance.  
1.3 Non-significant Risk Medical Device Study 
 
The FDA considers other microcurrent transcutaneous devices (such as TENS 
devices) as nonsignificant risk devices for medical device studies.19  The Nu-V3 device 
used in this study reflects an investigational device that meets the definition of a 
nonsignificant risk device per review of the IRB.  
 
 
 2.0 STUDY OBJECTIVE 
 
The objective of this research study is to collect data which demonstrates the ability of 
the Nu-V3 device to offer relief from one or more of the following symptoms: pain, 
anxiety, depression, and/or sleeplessness.  The objective is to demonstrate the 
effectiveness of Nu-V3 for any or all of the four symptoms listed. 
 
3.0 STUDY PARTICIPANT SELECTION CRITERIA 
3.1 Inclusion Criteria 
● Participant is at least 18 years of age 
● Participant presents with one or more of the following symptoms: pain, 
depression, anxiety, and/or sleeplessness 
● Participant is capable of understanding the use and maintenance of the device 
● Participant is capable and agreeing to participate in the ongoing assessment 
● Participant has signed the Informed Consent Form 
● Participant can commit to follow all protocol study timepoints 
3.2 Exclusion Criteria 
• Participants with a Pacemaker 
• Participants with irregular heart rate or a heart rate lower than 60 beats per 
minute (bradycardia) 
• Have had a transplant within the last 2 years 
• Have had a heart attack or cardiac bypass surgery within the last 12 months 
• History of substance abuse, including prescription drugs, within the last 12 
months 
• Patients with complaints of dizziness or lightheadedness within the last 3 months 
• Women who are pregnant 

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• Participants with Diabetic Retinopathy 
• Current Ear infection 
• SBP < 100 and/or DBP < 60 
• History of uncontrolled bipolar disorder within the last 12 months 
• History of uncontrolled seizures within the last 12 months 
• History of Aneurysms 
• History of syncope within the last 12 months 
• Participants that have had a TIA or stroke within the last 12 months 
• Participants with health problems deemed at risk for the study by the Principal 
Investigator 
• Participants with any changes to Pain/Anxiety/Depression/Sleeplessness 
medications within last 60 days (participants that do not meet this medication- 
change washout period may be delayed until 60-day period is met) 
• Participants that are currently under adjudication process for disability support, 
VA or other 
 
4.0 STUDY PROTOCOL  
 
The Nu-V3 Clinical Study is a prospective, single-arm, open-label, multi-center study 
using the Nu-V3 cranial nerve stimulation treatment device in patients with pain, 
anxiety, depression, and/or sleeplessness. 
 
For this Phase I study, a total of 50-100 patients at multiple centers will be registered 
for study participation.  Study participants are those who have signed the informed 
consent form, met the inclusion and exclusion criteria, and are enrolled in the study at 
one of multiple sites. Enrolled participants are stratified based on their pain, anxiety, 
depression, and/or sleeplessness symptom presentation at baseline and treated with 
the Nu-V3 device for 8 weeks, then observed for an additional 4 weeks. Interim 
analysis of reported data will be based on baseline stratifications and conducted at 4, 8, 
and 12 weeks during this time.  Post study, participants will be given the chance to 
continue with an optional maintenance treatment with the Nu-V3 device per a 2-weeks 
on, 2-weeks off schedule, for an additional 12 weeks, with an 8-week observation. 
 
Subjects enrolled onto the Nu-V3 Clinical Trial will undergo the following regimen: 
 
● At the baseline visit, patients will be asked to complete study questionnaires 
(Appendix 11) regarding all of the following symptoms: pain, anxiety, depression, 
and/or sleeplessness, as well as their quality of life, active medications, medical 
history, and demographical information. 
● At each subsequent visit, patients will be asked to complete study 
questionnaires regarding all the following symptoms: pain, anxiety, depression, 
and/or sleeplessness, as well as their activity level and quality of life. 
● The sessions will begin with the Nu-V3 device being placed on the left ear and 
three small pads (non-invasive) being placed on the ear.  Each Nu-V3 device 

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lasts for up to 14 days with a change in the pads approximately 7 days into the 
treatment. 
● Each session takes approximately 15-20 minutes. The placement of the device 
takes approximately 5 minutes and the remaining time is spent verifying ePRO 
form completion, and evaluating the patient for all device effects. 
● The Nu-V3 device is mobile and is worn externally on the left ear 24 hours a day 
during treatment, fitting comfortably behind the ear. An electrical signal is sent to 
the external ear through coated wire leads attached to the device and adhesive 
pads which attach to three sites on the ear. 
● Participants should be able to perform their typical day-to-day activities while 
wearing the device. They may shower while wearing the Nu-V3 device, provided 
that they do not get the device wet and use the small disposable ear covers that 
are provided for them. 
● Patients should not change their existing forms of treatment or medications 
without discussion with the investigator. 
● Nu-Life reserves the right to capture video, photographs and written testimonials 
from patients with written permission. In the event subjects elect to participate in 
any or all of these activities, they will be asked to sign a waiver giving exclusive 
rights to Nu-Life for the materials gathered from the patient, such as video, 
photographs and written testimonials. Their participation in this study is not 
dependent upon their willingness to provide these testimonial materials.  
4.1 Phase I Study Assessment Tables 
 

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4.2 Protocol Deviations 
In the event the Nu-V3 device is inadvertently removed or the device comes off, the 
participant will contact the Principal Investigator. The Principal Investigator will 
determine the appropriate course of action to be taken.   
If the study participant is unable to wear the device on their left ear, the study 
participant will be allowed to wear the device on their right ear, which will result in a 
minor study deviation. Left-ear deviations could be due to discomfort, sleep position, 
pain at the local site, or infection. A lack of significant improvement by the end of week 
4, per the Principal Investigator’s discretion, can also result in a deviation from left-ear 
placement.  
 
Device placement should be recorded on the study treatment form within the electronic 
data capture system. 
 
 
 5.0 DATA COLLECTION AND RETENTION 
 
The study endpoints data will be collected from each participant’s study 
questionnaires. The data will be collected electronically via the patient’s own device, 
and uploaded to an electronic data capture system.  Only patient data from the 
stratified indication(s) will be used for analysis of symptom response. The data will be 
used to demonstrate that the Nu-V3 device provides participants with relief of the 
symptoms of pain, depression, anxiety and/or sleeplessness. The data analysis will 
include comparative data for each participant’s questionnaire prior to beginning 
treatment with the Nu-V3 device, the participant’s weekly questionnaires during 

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treatment and the questionnaire completed at the end of the treatment with the Nu-V3 
device. 
Interim analyses of available data will be regularly submitted to the FDA for review. 
The Principal Investigator at each site will be responsible for recording, collecting, and 
storing the research participant’s study data.  The written records must be stored in a 
secure location.  Only the Principal Investigator or designated study staff will have 
access to the study records and all electronic files will be password protected. The 
Principal Investigator will also maintain adequate records for the study including:   
● all correspondence with the IRB and Sponsor 
● other pertinent data related to the study 
All records are to be retained by the Principal Investigator for a period of seven (7) 
years following the closure of the study. Following study closure, the Principal 
Investigator shall inform Nu-Life of the location of study records and storage changes 
(i.e. the Principal Investigator leaves the institution where the study was conducted). In 
such cases, the study records may be transferred to another institution, investigator, or 
to Nu-Life upon written agreement between the Principal Investigator and Nu-Life. 
 
 
6.0 DATA DISCLOSURE AND SUBJECT CONFIDENTIALITY 
Medical record confidentiality and data protection will be maintained at every visit. 
Subject medical information obtained as a result of this study is considered confidential 
and disclosure to third parties, other than those noted below, is prohibited. Data 
generated during this study is to be available for inspection on request by the FDA or 
other government regulatory agency auditors, the Sponsor's authorized 
representatives, and the IRB. 
 
 
7.0 ADVERSE EVENT(S) 
 
Potential unanticipated problems require prompt reporting to the central IRB and study 
sponsor. These problems potentially place subjects or others at greater risk of physical 
or psychological harm than was previously recognized, and warrant consideration of 
substantive changes in the protocol or informed consent process or other action in 
order to protect the safety, welfare, or rights of participants.  The central IRB must be 
notified within 5 calendar days of the event and the study sponsor within 24 hours.  The 
completed IRB Unanticipated Problem Form (Appendix 7) must be received by the 
central IRB within 10 calendar days of the event to avoid a major deviation. 
 
Unanticipated problems are defined as those problems which alter the risks to subjects 
or others.  This includes any study suspensions or holds.  This form will be used to 
report any problem that is unforeseen or involves risk.  One form will be used per event 
or problem. 

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8.0 STUDY ENDPOINT and DATA ANALYSIS 
 
8.1 Primary Endpoints: Primary endpoints consisted of the following: 
 
Safety: The primary safety endpoint is the occurrence of reported unanticipated 
problems involving risk to subjects or others (“UPIRTSOs”). These UPIRTSOs 
are defined as those problems which alter the risks to subjects or others.  This 
includes any study suspensions or holds. The primary safety endpoint analyses 
will be based on a risk-benefit conclusion. 
 
Effectiveness: The primary effectiveness endpoints are an overall change in 
median reported symptoms of pain, anxiety, depression, and/or sleeplessness 
via numeric rating scales at 8 weeks. This primary effectiveness is measured by 
median reported symptom changes in pain, anxiety, depression, and/or 
sleeplessness for respective stratified populations via the following validated 
tools: Pain - Pain Intensity and Interference (PEG_Scale), Anxiety - Generalized 
Anxiety Disorder 7-item (GAD-7) scale, Depression - Patient Health 
Questionnaire (PHQ-9), Sleeplessness - PROMIS short form 4a, and overall 
improvement of quality of life (QOL) - Patient’s Global Impression of Change 
(PGIC).  
The hypothesis-driven criterion of effectiveness is to show that there is a 
statistically significant reduction in the median reported pain, anxiety, 
depression, and/or sleeplessness levels of patients using the Nu-V3 device.  
The second criterion is intended to show that there is a statistically significant 
improvement in reported quality of life and perceived treatment benefit, 
secondary to overall reported symptom reductions of pain, anxiety, depression, 
and/or sleeplessness. 
 
8.2 Secondary Endpoints: Secondary endpoints consisted of the following:  
Effectiveness: The secondary effectiveness endpoint is an overall change in 
median reported symptoms of pain, anxiety, depression, and/or sleeplessness 
for respective stratified populations via numeric rating scales at 4, 8, and 12 
weeks. This is measured via the following validated tools: Pain – Pain Intensity 
and Interference (PEG_Scale), Anxiety - Generalized Anxiety Disorder 7-item 
(GAD-7) scale, Depression - Patient Health Questionnaire (PHQ-9), 
Sleeplessness - PROMIS short form 4a, and overall improvement of quality of 
life- Patient’s Global Impression of Change (PGIC). 
 
The patient’s perceived treatment benefit and device comfort information will be 
captured via the non-validated tool, Perceived Treatment Benefit Form (PTB-7). 
This effectiveness tool will measure median levels of reported perceived 
treatment benefit and device comfort. 

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The hypothesis-driven criterion is to show that there is a statistically significant 
reduction in the median reported pain, anxiety, depression, and/or sleeplessness 
levels of patients using the Nu-V3 device at weeks 4, 8, and 12.  The second 
criterion is intended to show that there is a statistically significant improvement in 
reported quality of life and perceived treatment benefit secondary to overall 
reported symptom reduction of pain, anxiety, depression, and/or sleeplessness 
at weeks 4, 8, and 12. 
8.3 Sub-Analyses: Sub-Analyses Consist of the following: 
 
The sub-analyses endpoints consist of the mean number of weeks that pain, 
anxiety, depression, and sleeplessness response are achieved and sustained, 
without utilization of another device, during the 8-week intervention.  In addition, 
study sub-analyses also include the mean number of weeks to initial benefit from 
Nu-V3 device use, and the mean medication dosage reduction of short acting 
pain, anxiolytics, and/or insomnia.  The device’s comfort-of-use, and patient’s 
perceived treatment benefit will also be captured for sub-analyses. 
 
 
9.0 STUDY MONITORING 
 
Nu-Life will monitor the study according to good clinical practice.  The Principal 
Investigator will work with a representative from Nu-Life to ensure the study is 
conducted according to this protocol and that all study matters are properly 
communicated. 
 
 
10.0 REFERENCES CITED 
 
1. 
Baxter AJ, Scott KM, Vos T, Whiteford HA. Global prevalence of anxiety disorders: a 
systematic review and meta-regression. Psychol Med. 2013 May;43(5):897-910. 
2. 
National Institutes of Health. U.S. Department of Health and Human Services, n.d. Web. 
25 Jan. 2017. 
3. 
Greenberg PE, Sisitsky T, Kessler RC, et al. The economic burden of anxiety disorders in 
the 1990s. J Clin Psychiatry. 1999 Jul;60(7):427-35. 
4. 
Ferrari, A.J., Somerville, A.J., Baxter, A.J., Norman, R., Patten, S.B., Vos, T. and 
Whiteford, H.A. (2013) ‘Global variation in the prevalence and incidence of major 
depressive disorder: a systematic review of the epidemiological literature’, Psychological 
Medicine, 43(3), pp. 471–481. 
5. 
Center for Behavioral Health Statistics and Quality. (2016). Key substance use and 
mental health indicators in the United States: Results from the 2015 National Survey on 
Drug Use and Health (HHS Publication No. SMA 16-4984, NSDUH Series H-51). 
Retrieved from http://www.samhsa.gov/data/  
6. 
PharmaPoint: Insomnia - Global Drug Forecast and Market Analysis to 2023. Feb-2015 

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7. 
Roth T. Insomnia: Definition, Prevalence, Etiology, and Consequences. Journal of Clinical 
Sleep Medicine : JCSM : official publication of the American Academy of Sleep Medicine. 
2007;3(5 Suppl):S7-S10. 
8. 
Mai E, Buysse DJ. Insomnia: Prevalence, Impact, Pathogenesis, Differential Diagnosis, 
and Evaluation. Sleep medicine clinics. 2008;3(2):167-174. 
9. 
Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in 
Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006 May;10(4):287-
333. 
10. Nahin RL. Estimates of pain prevalence and severity in adults: United States, 
2012. Journal of Pain. 2015;16(8):769-780. 
11. "2 Pain as a Public Health Challenge." Institute of Medicine. 2011. Relieving Pain in 
America: A Blueprint for Transforming Prevention, Care, Education, and Research. 
Washington, DC: The National Academies Press 
12. Ueno N et al. Innervation of the external ear in humans and musk shrew. Nihon Jibiinkoka 
Gakkao Kaiho. 1993 Feb;92(2):212-8. Japanese 
13. He W, Wang X, Shi H, et al. Auricular Acupuncture and Vagal Regulation. Evidence-
based Complementary and Alternative Medicine : eCAM. 2012;2012:786839. 
doi:10.1155/2012/786839 
14. Jean-Pierre Barral and Alain Croibier, Chapter 25 - Ear, In Manual Therapy for the Cranial 
Nerves, Churchill Livingstone, Edinburgh, 2009, Pages 227-238, ISBN 9780702031007, 
https://doi.org/10.1016/B978-0-7020-3100-7.50028-8. 
15. Torsten Liem, Chapter 17 - The organ of hearing and balance, In Cranial Osteopathy 
(Second Edition), Churchill Livingstone, Edinburgh, 2004, Pages 605-633, ISBN 
9780443074998, https://doi.org/10.1016/B978-044307499-8.50024-7. 
16. Terry Oleson, 2 - Theoretical Perspectives of Auriculotherapy, In Auriculotherapy Manual 
(Fourth Edition), Churchill Livingstone, Saint Louis, 2014, Pages 25-86, ISBN 
9780702035722, https://doi.org/10.1016/B978-0-7020-3572-2.00002-1. 
17. Review of the Uses of Vagal Nerve Stimulation in Chronic Pain Management. 
Chakravarthy K, Chaudhry H, Williams K, Christo PJ. Curr Pain Headache Rep. 2015 
Dec;19(12):54. doi: 10.1007/s11916-015-0528-6. Review. 
18. Pavlov VA, Tracey KJ. The vagus nerve and the inflammatory reflex—linking immunity 
and metabolism. Nature reviews Endocrinology. 2012;8(12):743-754. 
doi:10.1038/nrendo.2012.189. 
19. Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors,: U.S. 
Department of Health and Human Services, Food and Drug Administration, Center for 
Devices and Radiological Health (CDRH), January 2006, 
http://www.fda.gov/downloads/Regulatory Information/Guidances/UCM126418.pdf 

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Appendix 1: Informed Consent 
 

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Appendix 2:  Media Testimony Consent 
 
 

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Appendix 3: Study Process Maps 
 

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Appendix 4: Eligibility Checklist 
 
 

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Appendix 5: Instructions for Use 
 

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Appendix 6: Use and Care Instructions (Patient) 
 

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Appendix 7: IRB Unanticipated Problem Form 
 
 

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Appendix 8:  Medical History Form 
 
 

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Appendix 9:  Treatment Form 
 
 
 

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Appendix 10:  Medications Form 
 
 
 

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Appendix 11:  ePRO Questionnaires 
 
 

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