An Open-Label, Non-Controlled Study to Evaluate Outcomes of Pulsed Electromagnetic Field (PEMF) Therapy in Subjects With Various Pain Etiologies
Phase: NA
Conditions: Pain
Sponsor: Regenesis Biomedical, Inc.

710-6505-01 B 
CONFIDENTIAL 
CLINICAL STUDY PROTOCOL 
 
Study Title:  
An Open-Label, Non-Controlled Study to Evaluate Outcomes of 
Pulsed Electromagnetic Field (PEMF) Therapy in Subjects with 
Various Pain Etiologies 
Protocol Number: 
 
RBI.2015.005 
Version: 
 
 
B  
 
Phase:  
 
 
Post-Market  
Sponsor: 
Regenesis Biomedical, Inc. 
 
5301 N. Pima Road 
 
Scottsdale, AZ 85250 
 
Medical Contact: 
 
Adrianne P.S. Smith, M.D. 
 
 
 
 
Vice President, Clinical Business and Education 
 
 
 
 
Regenesis Biomedical, Inc. 
 
 
 
 
 
 
Final Approval Date:  
18 January 2017  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL SIGNATURE PAGE – SPONSOR 
 
Study Title:  
An Open-Label, Non-Controlled Study to Evaluate Outcomes of 
Pulsed Electromagnetic Field (PEMF) Therapy in Subjects with 
Various Pain Etiologies 
 
Protocol Number: 
RBI.2015.005 
 
Version: 
 
 
B 
 
The undersigned acknowledges that he/she has received and read Protocol RBI.2015.005, 
Version B, dated 18 January  2017. 
 
Sponsor Representatives 
Signature 
Date 
Adrianne P.S. Smith, M.D. 
Vice President, Clinical Business 
and Education 
 
 
Jamie Muhlenfeld 
Director Clinical Research  
 
 
 
 
 
 
 
 

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PROTOCOL SIGNATURE PAGE – Principal Investigator 
 
Study Title:  
An Open-Label, Non-Controlled Study to Evaluate Outcomes of 
Pulsed Electromagnetic Field (PEMF) Therapy in Subjects with 
Various Pain Etiologies 
 
Protocol Number: 
RBI.2015.005 
 
Version: 
 
 
B 
 
The undersigned acknowledges that he/she has received and read Protocol RBI.2015.005, 
Version B, dated 18 January 2017. 
 
Principal Investigator 
Signature 
Date 
 
 
 
 
 
 
 
 
 
 
 

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DOCUMENT REVISION HISTORY 
 
Date 
Summary of changes 
Version A 
01/11/2016 
Original document  
Version B  
1/18/2017 
Updated to include the Numeric Pain Rating Scale (NPRS), 
Clinical Global Impression – Global Improvement (CGI-I) 
Scale, Patient Global Impression of Change (PGIC) and 3-
Month follow-up and signature line for Dr. Smith. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Synopsis 
Study Title 
An 
Open-Label, 
Non-Controlled 
Study 
to 
Evaluate 
Outcomes of Pulsed Electromagnetic Field (PEMF) Therapy 
in Subjects with Various Pain Etiologies 
Protocol Number 
RBI.2015.005 
Name of Study Device 
Provant® Therapy System 
Phase of Development 
Post-Market 
Objective 
To obtain data on the safety and effectiveness of PEMF treatment 
in patients with various pain etiologies.  Data from enrolled 
patients will contribute to a patient registry on the post-market 
use of Provant. 
Number of Subjects 
Up to 300 subjects will be enrolled. 
Study Design 
This is an open-label, non-controlled trial in subjects with various 
pain etiologies at multiple centers in the US.  Eligible subjects 
will include those ≥ 22 years of age that have been deemed 
appropriate for treatment with Provant by the study investigator 
(prescriber).  Subjects will treat based on the treatment prescribed 
(location, frequency, duration) by the study investigator.   
Assessments 
Data from assessments administered as part of standard of 
practice will be obtained at baseline and, at a minimum, at the 
end of treatment.  Protocol required assessments will include 
baseline, interim visit / end of treatment visit and 3-month 
follow-up (post-treatment) pain scores using an 11-point numeric 
pain rating scale (NPRS), and a Clinical Global Impression – 
Global Improvement (CGI-I) Scale and a Patient Global 
Impression of Change (PGIC) Scale administered at follow-up / 
end of treatment visits. If the investigator administers additional 
assessments during the course of treatment, the data will be 
collected. 
 
Safety will be assessed during office visits and through review of 
AE reports and concomitant treatments and medications. All 
concomitant drug or non-drug treatments used during the study 
will be recorded.  
 
Study Procedures 
Subjects 
will 
be 
evaluated 
for 
eligibility 
at 
the 
Screening/Enrollment Visit.   Following assessment of eligibility, 
subjects will be assessed using standard of practice baseline 
measures and the NPRS related to the location of treatment.   
Subjects will be instructed in the use of the device and will self-
treat as prescribed by the study investigator.  As part of the 
investigator’s standard of practice, subjects may be provided with 
a patient reported outcome form(s) for capturing their daily pain 

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scores, which may include a 11 point numerical pain score scale, 
or other patient-reported outcomes related to the pain etiology.  
Subjects will document outcomes as instructed by the site at the 
Enrollment Visit.  
The site will contact the subject via telephone or the subject will 
come for an interim visit at regular intervals (to be determined by 
the investigator based on treatment regimen and standard of 
practice) to assess subject adherence to treatment, completion of 
patient reported outcomes, NPRS, CGI-I, PGIC and any safety 
concerns and/or changes in concomitant treatments/medications.  
After up to 20 weeks of treatment, the subject will return to the 
clinic for a final assessment that will include the NPRS, CGI-I 
and PGIC.  Adverse events and changes in concomitant 
medications will be collected. 
Three months post-treatment, a follow-up phone call will be 
made to collect the NPRS. 
 
Study Device 
 
The study device is the Provant® Therapy System which delivers 
Pulsed Electromagnetic Field (PEMF) energy therapy. Each 
device will be identified by a unique serial number.  
 
Study Sample 
The anticipated enrollment in this study is up to 300 subjects. The 
study will be conducted at multiple (up to 25) sites. 
 
Outcome Measures 
Outcome measures will be assessed in order to allow for 
characterization of the response to PEMF therapy.  
 
Efficacy Assessments  
Outcome measures of response to treatment with Provant will be 
determined based on the pain and/or edema being treated.  The 
initial evaluations will include treatment of post-surgical hand 
edema, arterial insufficiency, diabetic peripheral neuropathy, 
abdominoplasty and other plastic surgeries, post-hernia surgical 
pain, and pelvic pain.  All outcome measures used as part of the 
standard of practice regimen will be non-invasive assessments 
e.g., pain scores, SF-36, ankle-foot scales, oxygen perfusion 
(MOXY), and diaries with some subjects.    Protocol required 
assessments will include the NPRS, CGI-I and PGIC. 
Subject adherence (compliance with the prescribed treatment 
regimen) will be assessed verbally during follow-up and upon 
completion of the treatment period.  A subject with complete 
adherence will be expected to have a usage meter reading of 1.0 
for every hour that the subject treated.  

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Statistical Considerations 
Safety summaries will be conducted on all subjects who undergo 
treatment.   
The summaries on the efficacy parameters will be conducted on 
subjects completing the given evaluation at that given time point.  
No imputation will occur.  If subjects need to discontinue the 
study prior to the prescribed treatment duration, attempts will be 
made to conduct the final visit evaluations at the time of 
discontinuation.   
Demographic and subject characteristics will be summarized 
using descriptive statistics.  Assessments that are measured on a 
continuous scale will be summarized descriptively using the 
mean, standard deviation, median, minimum, and maximum 
value by time.  Variables that are measured on a categorical scale 
will be summarized as a proportion of the population.  
The change from baseline will be summarized for assessments in 
common between subjects/sites and 95% confidence intervals 
constructed.   
Adverse events will be summarized using MedDRA categories 
and by severity and relationship.  Concomitant medications will 
be summarized by WHODrug categories. 
This is an open-label, non-controlled study with no formal 
hypothesis testing planned.  Data will be collected through an 
Electronic Data Capture system as part of a registry to evaluate 
the use of Provant post-market.   
 
  
 
 

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I. 
INTRODUCTION AND BACKGROUND ................................................................................... 11 
II. 
STUDY OBJECTIVES ............................................................................................................. 13 
III. 
STUDY DESIGN ................................................................................................................... 14 
A. 
STUDY DESIGN ................................................................................................................................. 14 
B. 
EFFICACY ASSESSMENTS ..................................................................................................................... 14 
C. 
SAFETY EVALUATION ......................................................................................................................... 14 
D. 
ELIGIBILITY CRITERIA .......................................................................................................................... 14 
1. 
Inclusion Criteria ........................................................................................................................... 14 
2. 
Exclusion Criteria .......................................................................................................................... 15 
E. 
RECRUITMENT .................................................................................................................................. 15 
F. 
RANDOMIZATION .............................................................................................................................. 16 
G. 
DEVICE DESCRIPTION ......................................................................................................................... 16 
1. 
Control Unit .................................................................................................................................. 16 
2. 
Disposable Applicator Covers. ...................................................................................................... 16 
3. 
Treatment Applicator Pad ............................................................................................................ 17 
H. 
LOGISTICS AND DEVICE ACCOUNTABILITY .............................................................................................. 18 
I. 
LABELING ........................................................................................................................................ 18 
J. 
PREPARATION AND ADMINISTRATION ................................................................................................... 18 
K. 
BLINDING ........................................................................................................................................ 18 
L. 
STUDY ASSESSMENTS ........................................................................................................................ 18 
1. 
Efficacy Assessments .................................................................................................................... 18 
2. 
Safety Assessments ...................................................................................................................... 19 
IV. 
STUDY PROCEDURES .......................................................................................................... 19 
A. 
VISIT 1 – SCREENING VISIT (DAY -14 TO 0) ........................................................................................... 19 
B. 
VISIT 2 – ENROLLMENT VISIT (DAY 0) .................................................................................................. 19 
C. 
TREATMENT PERIOD .......................................................................................................................... 20 
D. 
INTERIM VISITS ................................................................................................................................. 20 
E. 
END OF TREATMENT VISIT .................................................................................................................. 21 
F. 
TREATMENT ADHERENCE/STUDY COMPLIANCE ....................................................................................... 21 
G. 
PROTOCOL ADHERENCE ..................................................................................................................... 22 
H. 
CONCOMITANT MEDICATIONS ............................................................................................................ 22 
V. 
WITHDRAWAL PROCEDURES............................................................................................... 22 
VI. 
STATISTICAL CONSIDERATIONS ........................................................................................... 22 
A. 
STUDY POPULATIONS ........................................................................................................................ 23 
B. 
EFFICACY DATA SUMMARIES ............................................................................................................... 23 
C. 
ADVERSE EVENTS .............................................................................................................................. 23 
D. 
SAMPLE SIZE .................................................................................................................................... 23 

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VII. 
INFORMED CONSENT .......................................................................................................... 24 
VIII. 
INSTITUTIONAL REVIEW BOARD.......................................................................................... 24 
IX. 
TERMINATION OF THE INVESTIGATION ............................................................................... 24 
X. 
ADVERSE EVENTS AND UNANTICIPATED ADVERSE DEVICE EFFECTS ...................................... 25 
A. 
ADVERSE EVENTS .............................................................................................................................. 25 
B. 
ANTICIPATED ADVERSE DEVICE EFFECTS ASSOCIATED WITH PROVANT ....................................................... 26 
C. 
UNANTICIPATED ADVERSE DEVICE EFFECT (UADE) ................................................................................ 27 
XI. 
INVESTIGATOR’S FILES/RETENTION OF DOCUMENTS ........................................................... 27 
A. 
SOURCE DOCUMENTS AND BACKGROUND DATA .................................................................................... 28 
B. 
AUDITS AND INSPECTIONS .................................................................................................................. 28 
XII. 
MONITORING THE STUDY ................................................................................................... 28 
XIII. 
CONFIDENTIALITY OF TRIAL DOCUMENTS AND SUBJECT RECORDS ....................................... 29 
XIV. 
PUBLICATION OF DATA AND PROTECTION OF TRADE SECRETS ............................................. 29 
XV. 
REFERENCES ....................................................................................................................... 30 
APPENDIX A - TIME AND EVENTS SCHEDULE ....................................................................................... 32 
APPENDIX B – CLINICAL GLOBAL IMPRESSION -GLOBAL IMPROVEMENT (CGI-I) SCALE ......................... 33 
APPENDIX C – PATIENT GLOBAL IMPRESSION OF CHANGE (PGIC) SCALE .............................................. 33 
APPENDIX D – EXAMPLES OF DIARY COLLECTION TOOLS..................................................................... 34 
 
 
 

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LIST OF ABBREVIATIONS 
AE 
 
Adverse Event 
CFR   
Code of Federal Regulations 
CGI-I  
Clinical Global Impression – Global Improvement Scale 
eCRFs  
Electronic Case Report Form 
FBSS  
Failed Back Surgery Syndrome 
FDA  
Food & Drug Administration 
IRB 
 
Institutional Review Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHz  
Megahertz 
NPRS  
Numeric Pain Rating Scale 
PEMF  
Pulsed Electromagnetic Field 
PGIC  
Patient Global Impression of Change 
PRFE  
Pulsed Radio Frequency Energy 
PRN  
As Needed 
RF 
 
Radiofrequency 
RFID  
Radio Frequency Identification Device 
SAE   
Serious Adverse Event 
SAP   
Statistical Analysis Plan 
WHO  
World Health Organization 
 

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I. 
INTRODUCTION AND BACKGROUND 
This study is being conducted to evaluate the effectiveness of the pulsed electromagnetic energy 
fields provided by the Provant® Therapy System (Provant) to treat pain and edema of multiple 
etiologies.  Provant is a medical device manufactured by Regenesis Biomedical, Inc. (Scottsdale, 
AZ), that has been cleared by the FDA (K972093, K091791, and K131979) “for adjunctive use in 
the palliative treatment of post-operative pain and edema of soft tissue.” The device delivers self-
administered, non-thermal, non-ionizing pulsed electromagnetic energy to the target tissue, using 
27.12 MHz pulses lasting 42 microseconds and delivered 1000 times per second.  The system 
generates an electromagnetic field that is continuously monitored and regulated to ensure consistent 
dosing. The therapeutic electromagnetic field is delivered by means of an applicator pad that is 
placed against the treatment site. The device is non-invasive and does not require placement of 
surface or deep electrodes, nor removal of bandages or clothing. Treatment is usually imperceptible 
and very well tolerated. Evidence suggests that Provant can reduce pain, promote healing, and 
promote restored range of motion following reparative surgery in wounded extremities. [Guo 2011, 
Moffett 2011]  As an analgesic, it is non-addictive and does not alter the mental state of the user.  
Regenesis Biomedical, Inc., has marketed Provant since 2004 and has treated over 11,500 patients 
within the U.S.  Over two million individual treatments have been administered with rare adverse 
events reported. [FDA MAUDE Database 2014]  In addition, the safety of PEMF has been well 
documented. The 2012 meta-analysis by Guo et al [Guo 2012] of 25 clinical trials of PEMF in 
treatment of pain, edema and wound healing identified no serious adverse events among 1,332 
patients treated with PEMF. In addition, the same meta-analysis found statistically significant 
evidence supporting the efficacy of adjunctive PEMF therapy for pain relief, edema reduction, and 
wound healing promotion.  Finally, adjunctive PEMF therapy has been reported effective in 
alleviating pain resulting from trauma, [Comorosan 1991, Foley-Nolan 1992, Wilson 1972, Barclay 
1983, Pennington 1993, Shandles 2002] and chronic pain. [Foley-Nolan 1990, Wagstaff 1986, 
Brook 2012]. 
In vitro and in vivo evidence suggest PEMF functions by modulating factors involved in pain 
signaling and soft tissue repair. In vitro studies demonstrated that Provant treatment of cells in 
culture can mediate wide-spread changes in transcript levels encoding factors involved in pain and 
the inflammatory response (including endogenous opioids, growth factors, cytokines, and cell cycle 
regulating factors), [Moffett 2011, Moffett 2012, Rohde 2010] and can promote cell proliferation. 
[George 2002]  Regenesis Biomedical, Inc. scientists recently found that PEMF increases 
endogenous opioid expression, which coincides with an increase in endothelin receptor B in 
keratinocytes, suggesting that PEMF treatment induces a localized analgesic effect by activation of 
these receptors by endothelin-1. [Moffett 2012a, Moffett 2012b]  These findings have led to the 
proposition that PEMF activates peripheral endogenous opioids which, in turn, activate an analgesic 
cascade via the endothelin pain axis. In a recent clinical study, PEMF usage for post-operative pain 
not only reduced pain levels and opioid consumption relative to sham-treated patients, but was also 
associated with lower IL-1ß levels in post-operative wound exudates. [Rohde 2010]  Together, these 

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findings suggest that PEMF therapy reduces pain both by modulating inflammation and by 
activating peripheral endogenous opioids. 
An exploratory prospective single-arm open-label IRB-approved study was recently conducted at 
four geographically distributed sites using the Provant device to treat persistent postoperative 
failed-back surgery syndrome (FBSS) pain. Thirty FBSS subjects with moderate to severe axial 
back and/or radicular leg pain were treated for 45 days with twice-daily Provant PEMF therapy. 
[Harper 2015]. 
Subjects were eligible for enrollment if they had a history of 1 or 2 lumbar spine surgeries with 
persistent axial and/or radicular leg pain 3 to 36 months (inclusive) following the most recent 
lumbar spine surgery, and had a mean Pain Intensity score of 4 or greater (0-10 numeric pain rating 
scale) for either axial or radicular pain during a 5-day run-in baseline period.  
Thirty subjects in this study were evaluated for the effectiveness of the Provant Therapy System in 
the treatment of post-surgical pain after back surgery.  Provant treatment twice daily for 45 days 
was associated with improved pain scores, improved overall well-being, improved physical 
function, and reduced analgesic consumption, especially in subjects who had undergone a 
discectomy.   
The purpose of the current study is to confirm the findings of pain relief observed in patients 
receiving treatment with Provant in a “real-world”, post-market setting.  Data from this study may 
be combined with other studies conducted in the post-market setting, i.e., in a patient registry.   
 
 
 
 
 
 

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II. 
STUDY OBJECTIVES  
This study is designed to provide post-market evidence of the safety and effectiveness of 
the Provant Therapy System for improving pain and edema in subjects with multiple pain 
etiologies. 

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III. 
STUDY DESIGN 
A. 
Study Design 
The study is an open-label, non-controlled study of the safety and effectiveness of 
investigator determined Provant therapy in subjects with pain and/or edema from various 
pain etiologies.   
B. 
Efficacy Assessments  
Outcome measures of response to treatment with Provant will be determined based on the 
location of the subject’s treatment area.  Protocol required assessments will include baseline 
and interim / end of treatment visit and 3-month follow-up (post-treatment) pain scores 
using an 11-point numeric pain rating scale (NPRS), and a Clinical Global Impression – 
Global Improvement (CGI-I) Scale and a Patient Global Impression of Change (PGIC) 
Scale. All outcome measures used in the investigator’s standard of practice are non-invasive 
assessments, e.g., pain scores, SF-36, ankle-foot scales, oxygen perfusion (MOXY), and 
diaries with some subjects.     
C. 
Safety Evaluation 
All observed and reported adverse effects will be recorded by the research staff. Start dates, 
end dates, frequency, severity of the event, any treatment required to treat the event, and the 
investigator’s judgment on causality and relationship to the device will be assessed for each 
AE. Any AE occurring after the signing of the informed consent form will be recorded. 
Only those AEs occurring after initiation of the first treatment with the study device will be 
considered treatment-emergent AEs. 
Adverse events will be mapped to preferred terms and body systems using the Medical 
Dictionary for Regulatory Activities (MedDRA) coding dictionary. While the primary 
presentation of adverse events will be subject-based, the number of adverse events will also 
be reported. The number and percentage of subjects reporting each event will be 
summarized.  Incidence of adverse events by maximum reported severity will also be 
tabulated. Serious adverse events and adverse events leading to discontinuation will be 
displayed.  
D. 
Eligibility Criteria 
Eligibility for participation in this study will be based on the inclusion/exclusion criteria.  
An individual subject may only be included in the study once.   
1. Inclusion Criteria 
1. Subject age is greater than or equal to 22 years. 
2. Subject has pain (chronic or acute) and/or edema that the prescriber deems treatment 
with Provant is warranted. 

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3. Subject is willing and able to give written informed consent.  
4. Female subjects must be post-menopausal, surgically sterile, abstinent, or practicing (or 
agree to practice) an effective method of birth control if they are sexually active for the 
duration of the study. (Effective methods of birth control include prescription hormonal 
contraceptives, intrauterine devices, double-barrier methods, and/or male partner 
sterilization). 
2. Exclusion Criteria 
1. Subject requires or anticipates the need for surgery of any type during the duration of 
treatment. 
2. Subject has received any investigational drug or device within 30 days or 5 half-lives of 
the drug, whichever is longer, prior to the Screening Visit or is enrolled in another 
clinical trial. 
3. Subject has used systemic corticosteroids within 2 months of the Screening Visit. 
4. Subject has a history of a solid tumor that is not in complete remission for greater than 
2 years other than successfully treated non-metastatic basal cell or squamous cell 
carcinomas of the skin in the treatment area. 
5. Subject has a history of blood cancer (e.g., leukemia, lymphoma, multiple myeloma). 
6. Subject has a serious psychosocial co-morbidity. 
7. Subject has a history of drug or alcohol abuse within one year prior to the Screening 
Visit. 
8. Subject has an implanted pacemaker, defibrillator, neurostimulator, spinal cord 
stimulator, bone stimulator, cochlear implant, or other implanted device with an 
implanted metal lead(s). 
9. Subject is currently pregnant or planning on becoming pregnant during the treatment 
period. 
10. Subject has been previously treated with the Provant Therapy System. 
11. Subject is unwilling or unable to follow study instructions, or comply with the treatment 
regimen and study visits. 
E. 
Recruitment  
Study subjects will be drawn from the investigative site.  

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F. 
Randomization 
This is an open-label study.  No subject randomization will occur.  Each Provant Therapy 
System will have a unique serial number that will be recorded on the eCRFs.  
G. 
Device Description  
The Provant Therapy System is a solid-state, fixed-power output radio frequency generator 
and transmitter designed to operate at the Federal Communication Commission authorized 
medical device frequency of 27.12 MHz.  The Provant System’s primary components are 
the Control Unit, the Treatment Applicator that generates and delivers the shortwave RF 
energy, and single-use Disposable Applicator Covers intended to minimize contagion 
transmission and help protect the Treatment Applicator from biological contamination.  Key 
functions and features of these components are as follows: 
1. Control Unit   
The Control Unit contains the main electronics, software, and user interface of the 
Provant System.  The Control Panel has a Therapy Start/Stop Switch and two Therapy 
Status Indicators, described below, which are located on the top of the Control Panel, as 
well as a Usage Meter on the side of Control Panel.   
Pressing the Therapy Start/Stop Switch initiates a preset, thirty (30)-minute therapy 
session by starting the Radio Frequency Identification Device (RFID) Tag interrogation 
and treatment sequence described in greater detail below.  Pressing the Therapy 
Start/Stop Switch again after a therapy session has started will stop the RF energy 
generation.  When pressed, the therapy Start/Stop switch generates an audible tone to 
inform the user that therapy is being initiated or terminated. 
The two Therapy Status Indicators on the Control Panel indicate when therapy is 
underway and the amount of time (in minutes) remaining in the therapy session.  When 
treatment is initiated, the message “CPI RUNNING” is displayed and green bars scroll 
from left to right across the indicator window.  When the thirty-minute therapy session 
is concluded, the generation of RF energy is automatically terminated, the Therapy 
Status Indicator windows go blank, and a brief audible beep is generated to alert the user 
that the treatment is finished. The user will then be instructed to turn off the Power 
Switch, remove the used Disposable Applicator Cover, and store the Treatment 
Applicator and cable until the next use.   
2. Disposable Applicator Covers.   
The Provant Therapy System features Disposable Applicator Covers, which are placed 
over the Treatment Applicator (described below) before each therapy session.  The 
Disposable Applicator Covers of the Provant Therapy System are single-use-only and 
are intended to minimize contagion transmission and help protect the Treatment 
Applicator from biological contamination.  Embedded in the Disposable Applicator 

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Covers is RFID reader functionality that is controlled by software in the Provant Control 
Unit.  This software prevents the reuse of a Disposable Applicator Cover by confirming 
that a new Disposable Applicator Cover is in place before allowing the generation and 
delivery of the therapeutic RF energy.  If the user attempts to reuse a cover, the device 
recognizes the RFID tag on the cover at start up as “used” and will generate an audible 
alert to inform the user to replace the used cover with a new cover.  If the user attempts 
to use the device without a Disposable Applicator Cover in place over the Treatment 
Applicator, the device will generate an audible alert to remind the user to place a new 
cover.  In either scenario, the Provant Therapy System will not initiate a therapy session 
until a new Disposable Applicator Cover is in place. The used Disposable Applicator 
Covers will be discarded as standard (not bio-hazard) waste. 
3. Treatment Applicator Pad  
The Provant Therapy System delivers pulsed RF energy to the desired treatment area 
via a spiral antenna in the Treatment Applicator Pad.  The Treatment Applicator Pad 
contains a therapy emitter, an antenna matching circuit, and an RF therapy measuring 
circuit.  The RF therapy measuring circuit automatically detects the level of RF signal 
that is radiated from the Treatment Applicator Pad and sends this information to the 
controller for the RF Generator.  This feedback circuit is used to regulate the RF therapy 
level, as the RF circuit reactance changes due to changes in body capacitance.  In this 
way, the correct energy output is constantly monitored, regulated, and maintained at the 
preset therapy dose levels. 
The Provant Therapy System generates pulsed RF energy using a highly efficient 
Class-C RF amplifier.  Subjects will receive treatment  consisting of a pulse duration of 
42 ± 4 microseconds, repeated every 1000 ± 25 microseconds, resulting in an output 
duty cycle of 4.2%, and requiring an average RF forward power level of <3 watts.  The 
energy is transferred via cable and emitted by the radiator located on the Treatment 
Applicator Pad circuit board for the preset 30-minute duration of therapy.  
The amount of forward RF energy emitted from the Treatment Applicator Pad is preset 
at 591 ± 44 V/m at a distance of 5.0 cm from the radiating surface of the Treatment 
Applicator Pad.  The amount of radiated RF energy diminishes with increasing distance 
from the radiating surface of the Treatment Applicator Pad.  Pulse rate, pulse width, and 
therapy session duration are regulated by the digital control component of the RF circuit 
board sub-assembly.  If the RF therapy measuring circuit in the Treatment Applicator 
Pad detects an absent or out of range therapy dosage level, treatment will not occur and 
the message “Service Required” will be displayed on the LED indicator window. In such 
an event, the Research Center will trouble shoot the issue as instructed in the Instructions 
for Use which accompanies the Study Device, and if unsuccessful in resolving the 
matter, will contact the sponsor to access a replacement device.   

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H. 
Logistics and Device Accountability 
 
The investigator or delegated designee will ensure that all study devices are stored in a 
secured area, in accordance with applicable regulatory requirements.  
Study device accountability will be overseen by the study site. These records should contain 
the dates dispensed to specified subject, dates returned to the site and sponsor, quantities of 
device received by the investigator and Provant serial number. These inventories, along with 
shipment receipts must be made available for inspection by the sponsor or designees and all 
regulatory agency inspectors. At the conclusion of the study, photocopies of all study device 
accountability records must be provided by the site to the sponsor. 
I. 
Labeling 
The Provant Therapy System will be labelled per commercial labelling which includes the 
Instruction for Use Manual and product labelling with product name and serial number. 
J. 
Preparation and Administration  
Each subject will receive one device to use.  All treatment sessions will be self-administered 
by the subject or his/her family or caregiver in the home or similar setting. 
Subjects will assume a comfortable position and place the treatment applicator pad of the 
Provant device on the location as identified by the investigator. Treatment will be 
administered continuously for 30 minutes. Thereafter, subjects will self-administer 
treatments as prescribed by the investigator.  
Prior to initiation of each treatment session, the subject will take the Treatment Applicator 
Pad of the study device and insert it into a new Disposable Applicator Cover. When inserted 
properly, the yellow starburst logo on the Treatment Applicator Pad is aligned with the same 
logo on the Disposable Applicator Cover, and the words “This side towards patient” will be 
visible through the clear window of the Disposable Applicator Cover.  When applied to the 
treatment area, the side of the Treatment Applicator Pad with the yellow starburst logo is 
directed toward the treatment location.  Further directions for use of the Provant Therapy 
System are found in the Instruction Manual.  Upon completion of the treatment session, the 
subject will remove and discard the Disposable Applicator Cover, and store the Provant 
device until the time of the next scheduled treatment session.  Disposable Applicator Covers 
may be discarded as standard waste. 
K. 
Blinding 
This is an open-label study.  No blinding will occur.   
L. 
Study Assessments 
1. Efficacy Assessments 
Efficacy assessments conducted during the Enrollment Visit (Day 0) and, at a minimum, at 
the completion of treatment will be collected.  

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Outcome measures of response to treatment with Provant will be determined based on the 
location of the subject’s treatment area.  Protocol required assessments will include baseline 
and interim / end of treatment visit and 3-month follow-up (post-treatment) pain scores 
using an 11-point numeric pain rating scale (NPRS), and a Clinical Global Impression – 
Global Improvement (CGI-I) Scale and a Patient Global Impression of Change (PGIC) 
Scale. All outcome measures administered as part of non-invasive standard of practice 
assessments will be collected, e.g., pain scores, SF-36, ankle-foot scales, oxygen perfusion 
(MOXY), and diaries with some subjects.  
2. Safety Assessments 
Safety will be assessed through review of AE reports and concomitant treatments and 
medications. All concomitant drug or non-drug treatments used will be recorded. Safety 
outcomes will be assessed at office visits as defined by the treatment regimen. 
IV. 
STUDY PROCEDURES  
 
The study procedures are summarized in the Schedule of Events (Appendix A) and described 
immediately following:  
A. 
Visit 1 – Screening Visit (Day -14 to 0)  
The Screening Visit will take place no more than 14 days prior to the Enrollment Visit.  If 
a successfully screened subject falls out of the 14-day limit, the subject will require another 
screening to participate.  The following procedures will be performed: 
1. Informed consent review and signature. 
2. Review Inclusion and Exclusion criteria. 
3. Collect subject demography data (including age, weight, height, gender, and 
race/ethnicity). 
4. Collect Medical and Surgical History.  
5. Review and record all concomitant medications. 
6. Perform a urine pregnancy test for females of child bearing potential. 
7. If the subject meets the eligibility criteria, continue on to the Enrollment Visit. 
If subject does not require any washout for prohibited medications or procedures, the 
Screening Visit and the Enrollment Visit can be conducted concurrently.   
 
B. 
Visit 2 – Enrollment Visit (Day 0) 
  The following procedures will be performed: 
1. Review Inclusion/Exclusion criteria (if Screening/Enrollment visits not combined). 

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2. Review and record any changes in medical history and study eligibility criteria since 
screening (if Screening/Enrollment visits not combined). 
3. Review and record adverse events (if Screening/Enrollment visits not combined). 
4. Review 
and 
record 
any 
changes 
in 
concomitant 
medications 
(if 
Screening/Enrollment visits not combined). 
5. Conduct baseline efficacy assessments. 
Response to treatment with Provant will be determined based on the location of the 
subject’s treatment area.  Assessments will include the NPRS and  non-invasive 
assessments  part of the investigator’s standard of practice e.g., pain scores, SF-36, 
ankle-foot scales, oxygen perfusion (MOXY), and diaries with some subjects. 
6. If the subject continues to meet eligibility criteria, enroll subject, and dispense study 
device. 
7. Introduce and train the subject on the use of the Provant Therapy System, including 
instructions for proper positioning and operation of the device.  
8. If applicable, distribute a patient diary and instruct the subject on how to complete.  
Examples of diary collection tools are provided in Appendix B. 
During this visit, eligible subjects will receive a Provant device and up to 120 Disposable 
Applicator Covers (packs of 30, depending on the anticipated treatment duration) and the 
subject will be instructed to administer treatment as prescribed by the investigator.  
C. 
Treatment Period 
Treatment may be self-administered by the subject, or with the assistance of a family 
member or caregiver.  Subjects will assume a comfortable position and place the treatment 
applicator pad of the Provant device centering the applicator pad on the treatment location 
as instructed by the investigator. Treatment will be administered for 30 consecutive minutes.  
Subjects will be asked to complete the patient reported outcome form(s) as instructed (as 
applicable). 
D. 
Interim Visits 
Subjects will be required to return to the clinic during the course of treatment as instructed 
by the investigator.  Telephone follow-ups may also be performed with each subject as 
determined by the investigator.  At these interim visits, the following will be collected if 
assessed: 
1. Review and record adverse events 
2. Review and record all concomitant medications 
3. Assess adherence to Provant treatment regimen  

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4. Assess completion of the patient reported outcome form(s), as applicable 
5. Conduct efficacy assessments: 
Response to treatment with Provant will be determined based on the location of the 
subject’s treatment area.  Assessments will include the NPRS, CGI-I, PGIC   and 
non-invasive assessments  part of the Investigators standard of practice e.g., pain 
scores, SF-36, ankle-foot scales, oxygen perfusion (MOXY), and diaries with some 
subjects. 
E. 
End of Treatment Visit  
Subjects will return to the clinic after completion of treatment as required by the study 
investigator. At this visit, the following procedures will be performed: 
1. Collect subject’s weight 
2. Review and record adverse events 
3. Review and record all concomitant medications 
4. Conduct efficacy assessments: 
Response to treatment with Provant will be determined based on the location of the 
subject’s treatment area.  Assessments will include the NPRS, CGI-I, PGIC   and 
non-invasive assessments  part of the Investigators standard of practice e.g., pain 
scores, SF-36, ankle-foot scales, oxygen perfusion (MOXY), and diaries with some 
subjects. 
5. Return of study device and unused DACs  
6. Return of the patient reported outcome form(s), as applicable.  Examples of diary 
collection tools are provided in Appendix B. 
F. 
Post-treatment Phone Call 
Three months after the End of Treatment Visit, subjects will be contacted via telephone 
and asked to rate their pain using the NPRS.  
G. 
Treatment adherence/study compliance 
Subject adherence (compliance with the prescribed treatment regimen) will be assessed 
during interim visits and upon completion of the treatment period by the research staff 
reading and recording the number displayed on the study device usage meter.  The usage 
meter will read 0.0 when dispensed. A subject with complete adherence will be expected to 
have a usage meter reading of 1.0 for each hour of treatment.  
Subjects will be instructed to return any unused DACs at the End of Treatment visit. 
Compliance will be assessed by counting the number of returned, unused DACs, and 
subtracting this from the total number of DACs dispensed (120).  As each treatment 
session requires one new DAC, compliance can be calculated based on the number of 
returned DACs relative to the prescribed regimen.  

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H. 
Protocol Adherence 
If protocol modifications are necessary, all alterations that are not solely of an 
administrative nature require a formal protocol amendment. 
If an investigator has deviated from the protocol in order to eliminate an immediate hazard 
to subjects or for other inevitable medical reasons, the investigator shall document all such 
deviations, including the reasons thereof, and immediately submit the documentation to 
the sponsor and to the IRB if required.   
I. 
Concomitant Medications 
All concomitant drug and non-drug treatments as well as the frequency of administration 
and indication for the treatment will be recorded in the subject’s chart. Based on the 
subject’s pain etiology, the investigator may disallow certain concomitant medications in 
order to accurately assess the effect of Provant therapy.  Opioid or other pain drug therapies 
may be reduced or discontinued during the treatment period of the study as directed by the 
subject’s treating physician.   
It is important to record the reason why each analgesic medication is being taken by the 
subject, specifically analgesics taken for treatment of pain/edema.  In this context, 
“analgesic medications” refers to medications prescribed and administered for the 
treatment of pain, and includes but is not limited to opioids, nonsteroidal anti-
inflammatory agents, anti-depressants and muscle relaxants.   
Prohibited Medications/Treatments 
The following medications and therapeutics are prohibited throughout the study: 
 Systemic steroids or topical steroids on the treatment location 
 Transcutaneous electrical neurostimulators (TENS units) 
 Implanted neurostimulators  
 Local injections  
 Intrathecal infusion 
 Acupuncture  
 Surgery 
V. 
WITHDRAWAL PROCEDURES 
If a subject or the prescriber decides to discontinue the subject’s treatment with the device, efforts 
will be made to perform all assessments scheduled for the End of Treatment Visit prior to subject 
withdrawal. 
VI. 
STATISTICAL CONSIDERATIONS  
The statistical analysis of the study is described in detail in a separate version-controlled Statistical 
Analysis Plan (SAP).  However, the statistical methodology described in this section of the protocol 
will be the basis for the detailed SAP.   

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Where not otherwise specified, the last pre-treatment observation will be used as baseline for 
calculating post-treatment changes from baseline. All confidence intervals will use a significance 
level of 5%. 
A. 
Study Populations   
Safety summaries will be conducted on all subjects who undergo treatment.     
The effectiveness summaries will also be conducted on all subjects who undergo treatment.  
Subjects that do not attend the End of Treatment Visit will be excluded from the End of 
Treatment analyses. Subjects who complete the End of Treatment Visit will be assessed for 
efficacy regardless of the number of days of treatment received.  No imputation of data will 
occur.  
B. 
Efficacy Data Summaries 
Demographic and subject characteristics will be summarized using descriptive statistics.  
Assessments that are measured on a continuous scale will be summarized descriptively 
using the mean, standard deviation, median, minimum, and maximum value by time.  
Variables that are measured on a categorical scale will be summarized as a proportion of 
the population.  
The change from baseline will be summarized for effectiveness outcome assessments in 
common between subjects/sites and 95% confidence intervals constructed.     
Adverse events will be summarized using MedDRA categories and by severity and 
relationship.  Concomitant medications will be summarized by WHODrug categories. 
C. 
Adverse Events 
All adverse events will be coded according to Medical Dictionary for Regulatory Activities 
(MedDRA). Safety assessments will include treatment-emergent adverse events (TEAEs; 
adverse events that occur in subjects who undergo treatment).  Subjects with TEAEs will 
be summarized with frequencies and percentages by system organ class and preferred term, 
severity, and relationship to treatment for each treatment group.  Treatment-related adverse 
events will be defined as adverse events with investigator assessment of related or possibly 
related.  In summaries of TEAEs by severity and relationship to study device, subjects 
reporting multiple episodes will be counted once under the worst severity and the strongest 
relationship, respectively.  Serious Adverse Events will also be presented by relationship to 
treatment.  
The number of subjects with at least one adverse event will be tabulated.  The number of 
adverse events will also be tabulated.  The number of subjects and the number of adverse 
events will be tabulated by severity and relationship. 
D. 
Sample Size  

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This is an open-label, non-controlled study with no formal hypothesis testing planned.  It is 
anticipated that up to 300 subjects will be enrolled in this study.  Data from this study will 
be included in a patient registry. The statistical analysis plan for the patient registry will 
fully describe the methods used to evaluate data from this study.   
VII. 
 INFORMED CONSENT 
It is the responsibility of the investigator, or a person designated by the investigator (if acceptable 
by local regulations), to obtain written informed consent from each individual participating in this 
study after adequate explanation of the aims, methods, objectives and potential hazards of the study.  
It must also be explained to the subjects that they are completely free to refuse to enter the study or 
to withdraw from it at any time for any reason.  Appropriate IRB-approved forms for obtaining 
written informed consent will be provided by the investigator or by Regenesis Biomedical, Inc. or 
their designee. 
If new safety information results in significant changes in the risk/benefit assessment, the consent 
form will be reviewed and updated if necessary.  All subjects (including those already being treated) 
will be informed of the new information, given a copy of the revised form and be re-consented to 
continue in the study. 
VIII. INSTITUTIONAL REVIEW BOARD 
This protocol, the informed consent form and any accompanying material provided to the subject 
(such as subject information sheets or descriptions of the study used to obtain informed consent) as 
well as any advertising or compensation given to the subject, will be submitted by the investigator 
or investigator’s designee to an IRB.  Approval from the IRB must be obtained before starting the 
study and will be documented in a letter to the investigator specifying the date on which the IRB 
met and granted the approval. 
IX. 
TERMINATION OF THE INVESTIGATION 
As the study sponsor, Regenesis Biomedical, Inc. reserves the right to terminate the study at any 
time.  Should early termination be necessary, Regenesis Biomedical, Inc. and the investigator will 
consult and make sure that adequate consideration is given to the protection of subjects’ interests. 
Additionally, data will be reviewed by the sponsor on a regular basis.  Reports of data will be made 
available to the Institutional Review Boards and to the FDA as required.  Unanticipated adverse 
device events will be evaluated and reported in accordance with 21 CFR Part 812 requirements and 
as required by the governing IRB.  
This study will be suspended if the investigator or the sponsor, upon review and evaluation of the 
clinical data, finds the severity or incidence of single or total adverse events unacceptable for 
continuation of the investigation.  

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X. 
ADVERSE EVENTS AND UNANTICIPATED ADVERSE DEVICE EFFECTS 
A. 
Adverse Events 
An adverse event is defined as follows:  Any untoward medical occurrence in a patient or clinical 
investigation patient administered a medical device treatment which does not necessarily have to 
have a causal relationship with this treatment.  An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of study device treatment, whether or not considered related to the study 
device.   
All AEs occurring after signing of the consent form will be recorded. AEs arising subsequent to the 
time of initiation of first treatment with study device will be considered treatment emergent AEs.   
At each contact with the subject, the investigator or designee must seek information on AEs by non-
leading specific questioning and, as appropriate, by examination.  All observed or volunteered AEs, 
regardless of suspected causal relationship to study device, must be recorded in the patient’s chart. 
Any events involving illnesses or injuries with onset during the study or any events involving 
exacerbations of pre-existing illnesses should be recorded.  All clearly related signs and symptoms 
should be grouped together and recorded as a single diagnosis in the patient’s chart.  A pre-existing 
condition must not be reported as an AE unless the condition worsens during the trial.     
Each AE will be independently judged by the investigator in terms of causality.  The following 
definitions will be used for these causality assessments. 
Related:           
This causal relationship is assigned when the AE: 
 starts a reasonable time after study device administration, 
 cannot be reasonably explained by the subject’s clinical state. 
Possibly Related:  
This causal relationship is assigned when the AE: 
 starts a reasonable time after study device administration, but 
 could have been produced by the subject’s clinical state or other 
modes of therapy administered to the subject. 
Unrelated:       
This causal relationship is assigned when the AE: 
 is definitely not associated with the study device administered 
and is readily explained by other events or diagnoses. 
Each AE will also be independently judged by the investigator in terms of severity.  The following 
definitions will be used for these severity assessments. 
Mild:           
The event is transient (<48 hours) or causes mild discomfort; no medical 
intervention/therapy is required 
Moderate:  
The event results in mild to moderate limitation in activity – some assistance 
may be needed; no or minimal medical intervention/therapy is required 

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Severe:       
The event results in marked limitation in activity, assistance is usually 
required; medical intervention/therapy is required and hospitalization is 
possible 
Each AE will also be independently judged by the investigator in terms of seriousness.  A serious 
adverse event (SAE) is defined as any untoward medical occurrence that: 
 Results in death, or 
 Is life-threatening, 
Note: The term “life-threatening” in the definition of “serious” refers to an event in which 
the subject was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. 
 Requires inpatient hospitalization or prolongation of existing hospitalization, 
 Results in permanent impairment of a body function or permanent damage to a body 
structure,  
 Is a congenital anomaly/birth defect,  
 Necessitates medical or surgical intervention to preclude any one of the outcomes listed 
in this definition. 
All SAEs must be reported immediately (within 24 hours of knowledge of the event) by telephone 
and fax to the following: 
Sponsor Medical Contact – Adrianne P.S. (Patti) Smith, MD; Regenesis Biomedical Inc. 
Mobile: (480) 848-8671; Fax: (480) 718-8702; patti.smith@regenesisbio.com 
The investigator will follow up with a written description of the SAE submitted to the sponsor 
within 3 days, including the results of the SAE investigation and any treatment(s) provided.  
All adverse events will be followed until resolution or until the investigator assesses the subject’s 
status has returned to normal. 
B. 
Anticipated Adverse Device Effects Associated with Provant  
Anticipated adverse events associated with Provant, reported at least once since market launch in 2004, 
are as follows: 
 Device fails to operate 
 Warmth or burning at treatment site   
 Skin reaction at treatment site (tingling, pins-and-needles, rash, blisters, swelling, dry skin, 
redness, numbness, sensation of warmth)  
 Increased bleeding at surgical site 
 Chilliness 
 Headache 
 Malaise  
 Nausea 

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 Abdominal or chest wall discomfort 
 Muscle cramps 
 Failure to reduce pain or an increase in pain 
 Metallic taste in mouth 
 Exacerbation of tinnitus 
 Stiffness 
 Weakness 
 Dizziness/lightheadedness 
 Restless leg syndrome 
 Strong urine odor 
 GI/upset stomach 
 Excessive menstruation 
C. 
Unanticipated Adverse Device Effect (UADE) 
Unanticipated Adverse Device Effect means any serious adverse effect on health or safety or any 
life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence in the protocol or 
informed consent form, or any other unanticipated serious problem associated with the device that 
relates to the rights, safety, or welfare of subjects.   
All UADEs must be reported immediately (within 24 hours of knowledge of the event) by telephone 
and fax to the following: 
Sponsor Medical Contact – Adrianne P.S. (Patti) Smith, MD; Regenesis Biomedical Inc.; 
Mobile: (480) 848-8671; Fax: (480) 718-8702; patti.smith@regenesisbio.com 
The investigator will follow up with a written description of the UADE submitted to the sponsor 
within 3 days, including the results of the UADE investigation and any treatment(s) provided.  
Any UADE occurring up to the date of the final Follow-up Visit will be followed until it resolves, 
the investigator assesses the subject’s status to have returned to baseline, or until the investigator 
feels that the event is stable and chronic. 
The investigator shall submit to the reviewing IRB a report of any UADE occurring during an 
investigation as soon as possible in accordance with the IRB submission guidelines, but in no event 
later than 10 working days after the investigator first learns of the effect. 
XI. 
INVESTIGATOR’S FILES/RETENTION OF DOCUMENTS 
The investigator must maintain adequate and accurate records to enable the conduct of the study to 
be fully documented and the study data to be subsequently verified.  These documents should be 
classified into two different separate categories (1) Investigator’s Study File, and (2) Subject 
clinical source documents. The Investigator’s Study File will contain the protocol/amendments, 
data collection forms, Independent Ethics Committee/Institutional Review Board and governmental 
approval with correspondence, sample informed consent, device records, staff curriculum vitae and 

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authorization forms and other appropriate documents/correspondence. All records defined in 21 
CFR 812.140 will be kept on file. 
Subject clinical source documents include subject hospital/clinic records, physician’s and nurse’s 
notes, appointment book, original lab reports, special assessment reports, signed informed consent 
forms, subject screening and enrollment logs.   
The investigator must keep these two categories of documents on file for at least 2 years after the 
latest of the following: completion, discontinuation of the study, or the regulatory submission for 
which the study is being performed is no longer under review.  After that period of time the 
documents may be destroyed, subject to local regulations. 
Should the investigator wish to assign the study records to another party or move them to another 
location, Regenesis Biomedical, Inc. must be notified in advance. 
If the investigator cannot guarantee this archiving requirement at the investigational site for any or 
all of the documents, special arrangements must be made between the investigator and Regenesis 
Biomedical, Inc. to store these in a sealed container(s) off-site so that they can be returned sealed 
to the investigator in case of a regulatory audit.  Where source documents are required for the 
continued care of the subject, appropriate copies should be made for storing outside of the site. 
A. 
Source Documents and Background Data 
The investigator shall supply the sponsor on request with any required background data   
from the study documentation or clinic records.  This is particularly important when data 
requires clarification.  In case of special problems/and or governmental queries or requests 
for audit inspections, it is also necessary to have access to the complete study records, 
provided that subject confidentiality is protected.  
All forms should be typed or filled out using indelible ink, and must be legible.  Errors 
should be crossed out but not obliterated, the correction inserted, and the change initialed 
and dated by the investigator or his/her authorized delegate.   
B. 
Audits and Inspections 
The investigator should understand that source documents for this trial should be made 
available to appropriately qualified personnel from the Regenesis Biomedical, Inc. Quality 
Assurance Unit or its designees or to health authority inspectors after appropriate 
notification.  The verification of the data must be by direct inspection of source documents 
and patient charts. 
XII. 
MONITORING THE STUDY 
It is understood that the responsible Regenesis Biomedical, Inc. monitor (or designee) may contact 
and visit the investigator and will be allowed, upon request, to inspect the various records of the 
trial provided that subject confidentiality is maintained in accord with local requirements. 

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If a monitoring visit is scheduled, the monitor may inspect the patient charts for completeness, 
consistency and accuracy of the data captured.  The monitor should have access to laboratory test 
reports and other subject records needed.  The investigator (or his/her designee) agrees to cooperate 
with the monitor to ensure that any problems detected in the course of these monitoring visits are 
resolved. 
XIII. CONFIDENTIALITY OF TRIAL DOCUMENTS AND SUBJECT RECORDS 
The investigator must assure that subjects’ anonymity will be maintained and that their identities 
are protected from unauthorized parties.  On documents submitted to the sponsor, subjects should 
not be identified by their names, but by an identification code.  The investigator should keep a 
subject enrollment log showing codes, names and addresses.  The investigator should maintain 
documents not for submission to Regenesis Biomedical, Inc., e.g., subjects’ written consent forms, 
in strict confidence. 
XIV. PUBLICATION OF DATA AND PROTECTION OF TRADE SECRETS 
The results of this study may be published or presented at scientific meetings.  If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to Regenesis Biomedical, Inc. at least 
30 days prior to submission.  This allows the sponsor to protect proprietary information and to 
provide comments based on information from other studies that may not yet be available to the 
investigator. 
In accordance with standard editorial and ethical practice, Regenesis Biomedical, Inc. will generally 
support publication of multicenter trials only in their entirety and not as individual center data.  In 
this case, a coordinating investigator will be designated by mutual agreement.  Any formal 
publication of the study in which input of Regenesis Biomedical, Inc. personnel exceeded that of 
conventional monitoring will be considered as a joint publication by the investigator and the 
appropriate Regenesis Biomedical, Inc. personnel.  Authorship will be determined by mutual 
agreement. 

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XV. 
REFERENCES 
Barclay V, Collier RJ, Jones A. Treatment of various hand injuries by pulsed electromagnetic 
energy (Diapulse). Physiotherapy. 1983; 69: 186–188. 
Brook J, Dauphinee DM, Korpinen J, Rawe IM. Pulsed Radio Frequency Electromagnetic Field 
Therapy: A Potential Novel Treatment of Plantar Fasciitis. J Foot Ankle Surg 2012; 51(3):312-6 
Comorosan S, Pana I, Pop L, et al. The influence of pulsed high peak power electromagnetic 
energy (Diapulse) treatment on posttraumatic algoneurodystrophies. Rev Roum Physiol. 1991; 
28:77–81. 
FDA MAUDE and MDR databases searched on June 15, 2014 reveals 5 medical device reports 
related to PEMF in any indication. 
Foley-Nolan D, et al. Pulsed high frequency (27MHz) electromagnetic therapy for persistent neck 
pain. A double blind, placebo-controlled study of 20 patients. Orthopedics 1990; 13(4): 445-51. 
Foley-Nolan D, Moore K, Codd M, and et al. Low energy high frequency pulsed electromagnetic 
therapy for acute whiplash injuries: a double blind randomized controlled study. Scand J Rehabil 
Med. 1992; 24(1): 51-9. 
George FR, Lukas RJ, Moffett J, Ritz MC. In vitro mechanisms of cell proliferation induction: a 
novel bioactive treatment for accelerating wound healing. Wounds 2002; 14(3):107-115. 
Guo L, Kubat NJ, Isenberg RA. Pulsed radio frequency energy (PRFE) use in human medical 
applications. Electromagn Biol Med 2011; 30(1):21-45. 
Guo L, Kubat NJ, Nelson TR, Isenberg RA. Meta-analysis of clinical efficacy of pulsed radio 
frequency energy treatment. Ann Surg 2012;255(3):457-67. 
Harper WL, Schmidt WK, Kubat NJ, Isenberg RA.  An open-label pilot study of pulsed 
electromagnetic field therapy in the treatment of failed back surgery syndrome.  International 
Medical Case Reports Journal 2015;8:13-22 
Moffett J, Kubat NJ, Isenberg RA. Pulsed radio frequency energy as an effective pain treatment. 
Practical Pain Management 2011; 11(3):71-73. 
Moffett J, Fray L. Cellular and molecular mechanisms of peripheral pain inhibition by treatment 
with pulsed radio frequency energy: the role of endogenous opioid induction in human fibroblasts 
and keratinocytes. J Pain 2012; 13(4) Suppl: S42. 
Moffett J, Fray L, Kubat N. Activation of Endogenous Opioid Gene Expression in Human 
Keratinocytes and Fibroblasts by Pulsed Radio Frequency Energy Fields. Journal of Pain 
Research 2012; 5:347-357. 
Pennington G.M., et al., Pulsed, non-thermal, high-frequency electromagnetic energy (DIAPULSE) 
in the treatment of grade I and grade II ankle sprains. Mil Med, 1993. 158(2): p. 101-4. 
Rohde C, Chiang A, Adipoju O, Casper D, Pilla AA.  Effects of pulsed electromagnetic fields on 
interleukin-1beta and post-operative pain: a double-blind, placebo-controlled, pilot study in breast 
reduction patients.  Plast Reconstr Surg 2010;125(6):1620-27. 
Shandles I.D., Pruchniewski J., Reynolds K.L., Heel Neuroma: the enigma of recalcitrant heel pain 
and an innovative approach highlighting sixty surgical cases and a review of two hundred and fifty 

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seven symptomatic but non-surgical cases. The Foot, 2002. 12: 10-20.  
Wagstaff P., Wagstaff S., Downey M., A pilot study to compare the efficacy of continuous and 
pulsed magnetic energy [shortwave diathermy] on the relief of low back pain. Physiotherapy, 1986. 
72: p. 563-566. 
Wilson DH. Treatment of soft-tissue injuries by pulsed electrical energy. Br Med J 1972; 2: 269–
270. 
 

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APPENDIX A - TIME AND EVENTS SCHEDULE 
Period 
Screening 
Visit 
Enrollment 
(Baseline) 
Visit1 
Treatment 
Period 
Interim 
Visits 
End of 
Treatment 
Visit 
Follow-up 
Phone Call  
Study Day 
-14 to 0 
0 
As 
Prescribed 
As 
Prescribed 
As Prescribed 
3 months 
post-
treatment 
Informed Consent 
X 
 
 
 
 
 
Demographic Information 
X 
 
 
 
 
 
Medical/Surgical History 
X 
 
 
 
 
 
Urine Pregnancy Test2 
X 
 
 
 
 
 
Height and Weight 
X 
 
 
 
X7 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
 
 
Efficacy Outcomes Assessments 
(Including NPRS, CGI-I and PGIC) 
 
X3 
 
X3 
X3 
X3 
Study Device Training 
 
X4 
 
 
 
 
Dispense Study Device  
 
X 
 
 
 
 
Distribute Diary Collection Tool(s) 
 
X5 
 
 
 
 
Study Device Treatment 
 
 
X6 
 
 
 
Assess Adverse Events and Concomitant 
Medications 
X8 
X 
 
X 
X 
 
Assess Subject Adherence to Treatment 
 
 
 
X 
X 
 
Collect Diary Collection Tool(s) 
 
 
 
X 
X 
 
Return Study Device and Unused DACs 
 
 
 
 
X9 
 
1. 
The Screening Visit and the Enrollment Visit may occur on the same day in which case none of the screening tests 
need to be repeated.  
2. 
Urine pregnancy test will be performed on women of child-bearing potential.  
3. 
The CGI-I and PGIC will not be conducted at the Enrollment (Baseline) Visit. Only the NPRS will be captured at 
the Follow-up phone call.  
4. 
Introduction to and training on the study device will be completed during the Enrollment Visit. 
5. 
Distribution of a diary collection tool will occur if the investigator decides to use this as a means for capturing 
patient reported outcomes.  Completion of the forms will occur as instructed by the investigative site, as applicable. 
6. 
The subject will self-administer treatments as prescribed by the investigator. 
7. 
Collect only weight at End of Treatment Visit. 
8. 
Assessment of adverse events will be conducted after the signing of the Informed Consent. 
9. 
At the End of Treatment Visit subjects will return the study device and all unused Disposable Applicator Covers 
(DACs). 

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APPENDIX B – CLINICAL GLOBAL IMPRESSION -GLOBAL IMPROVEMENT (CGI-
I) SCALE 
 
 
 
APPENDIX C – PATIENT GLOBAL IMPRESSION OF CHANGE (PGIC) SCALE 
 
 
 

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APPENDIX D – EXAMPLES OF DIARY COLLECTION TOOLS 
Response to Study Device Form 
Day 1 - Day ____ 
 
 
Subject #: ____  ____ - ____  ____  ____  Subject Initials: ____  ____ ____ 
 
Instructions: Enter the date as instructed by your study investigator and select the one number that 
best indicates the average intensity of pain you have had over the last 24 hours in the area you are 
treating.  
 
Day 1 - Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
Day 2 - Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
Day 3 - Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
Day 4 - Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
Day 5 - Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
Day 6 - Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 

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Day ___  Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
 Day ___  Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
Day ___  Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
Day ___  Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
Day ___  Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
Day ___  Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
Day ___  Date: ______________ 
 
Pain Intensity Assessment (NPRS) Questionnaire 
 
 
 
         0         1          2          3         4          5          6          7         8         9         10 
 No Pain                                                                                                             Worst Pain Imaginable 
 
 
You have completed your Day 1 - Day ___ Forms.  Please return this packet to the clinic staff at 
your next Visit. 
 

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Medication Consumption  
Day 1 - Day ____ 
 
 
Subject #: ____  ____ - ____  ____  ____  Subject Initials: ____  ____ ____ 
 
Instructions: Enter the date as instructed by your study investigator and list the medication(s) taken 
for your pain in the provided field(s) along with the number of pills you have taken over the last 24 
hours.  
 
Day 1 - Date: ______________ 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
 
Day 2 - Date: ______________ 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
 
Day 3 - Date: ______________ 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
 
Day 4 - Date: ______________ 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
 
 
 
 
 
 
 

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Day ____ - Date: ______________ 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
 
Day ____ - Date: ______________ 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
 
Day ____ - Date: ______________ 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
 
Day ____ - Date: ______________ 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
 
Day ____ - Date: ______________ 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
 
Day ____ - Date: ______________ 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: 
 
Medication Name: 
 
 
Number of Pills Taken: