A Multi-Center, Sham-Controlled, Double-Blind Randomized Withdrawal Study of PEMF Therapy to Evaluate Vibration Perception Threshold and Thermal Sensory in Subjects With Diabetic Peripheral Neuropathy in the Lower Extremity
Phase: NA
Conditions: Diabetic Peripheral Neuropathy
Sponsor: Regenesis Biomedical, Inc.

710-7005-01 F 
CONFIDENTIAL 
CLINICAL STUDY PROTOCOL 
 
Study Title:  
A Multi-Center, Sham-Controlled, Double-Blind Randomized 
Withdrawal Study of Pulsed Electromagnetic Field (PEMF) 
Therapy to Evaluate Vibration Perception Threshold and 
Thermal Sensory in Subjects with Diabetic Peripheral 
Neuropathy in the Lower Extremity 
Protocol Number: 
 
RBI.2017.001 
Version: 
 
 
F  
 
Phase:  
 
 
Proof of Concept 
Principal Investigator: 
Dr. Arthur J. Tallis 
 
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:  
 June 16, 2017  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL SIGNATURE PAGE – INVESTIGATOR 
 
Study Title:  
A Multi-Center, Sham-Controlled, Double-Blind Randomized 
Withdrawal Study of Pulsed Electromagnetic Field (PEMF) 
Therapy to Evaluate Vibration Perception Threshold and 
Thermal Sensory in Subjects with Diabetic Peripheral 
Neuropathy in the Lower Extremity 
 
Protocol Number: 
RBI.2017.001 
 
Version: 
 
 
F 
 
 
The undersigned acknowledges that he/she has received and read Protocol RBI.2017.001, 
Version F, dated 16 JUN 2017. 
 
Investigator 
Signature 
Date 
 
 
 
 
 
 
 
 
 
 
 
 

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DOCUMENT REVISION HISTORY 
 
Date 
Summary of changes 
Version A 
10 JAN 2017 
Original document  
Version B 
10 FEB 2017 
Changed Painful Peripheral Diabetic Neuropathy to Diabetic 
Peripheral Neuropathy to allow for a broad symptomatology to 
be included.  Added information to how many times VPT test 
will be conducted to obtain the average value at each time point. 
Added additional primary endpoint to capture changes in both 
large and small nerve fiber responses.  Updated response 
assessment from VPT change to change in 1-point decrease in 
NPRS over the last 24 hours.  Added additional instruction and a 
visual for collecting the foot measurement, updated introduction 
and background section, and added additional medications to 
“allowed medications” section. Removed EQ-5D questionnaire 
and replaced with Neuro-QoL questionnaires. 
Version C 
22 FEB 2017 
Change testing of plantar aspect to dorsal aspect for QST heat 
and cold testing.  Updated Exclusion #3 added a timeframe of 
within 6 months of the Screening Visit and an upper limit of 1.4 
for the ABI. 
Version D 
27 MAR 2017 
Removed Summary of Diabetes Self Care Activities 
Questionnaire (SDSCA) to reduce patient fatigue with answering 
questionnaires.  Switched NeuroQoL questionnaire with a single 
neuropathy-and foot ulcer-specific quality of life instrument. 
Version E 
19MAY2017 
Updated locations for biopsies to be taken as well as the central 
lab used in analyzing the samples. 
Version F 
12JUN2017 
Increase the number of sites from 2 to 4.  Update 
Inclusion/Exclusion criteria to allow for a broader population to 
be enrolled.  Allow all patients to voluntarily consent to biopsies. 
 
 
 
 
 
 
 
 
 

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Study Synopsis 
Study Title 
A 
Multi-Center, 
Sham-Controlled, 
Double-Blind 
Randomized Withdrawal Study of Pulsed Electromagnetic 
Field (PEMF) Therapy to Evaluate Vibration Perception 
Threshold and Thermal Sensory in Subjects with Diabetic 
Peripheral Neuropathy in the Lower Extremity 
Protocol Number 
RBI.2017.001 
Name of Study Device 
PROVANT® Therapy System 
Phase of Development 
Proof of Concept 
Objective 
To demonstrate the effectiveness of PEMF treatment compared 
to sham treatment in changing Vibration Perception Threshold 
(VPT) and Thermal Sensory (QST) in patients with diabetic 
peripheral neuropathy (DPN) when treatment is administered 
twice daily through 120-day period.   
Number of Subjects 
Up to 40 subjects randomized 1:1. 
Study Design 
This is a multi-center, sham-controlled, double-blind, enriched 
enrollment, randomized withdrawal clinical trial conducted on 
subjects 
with 
bilateral 
symmetrical 
diabetic 
peripheral 
neuropathy. Eligible subjects will include those between 22 and 
80 years of age with Type 1 or Type 2 diabetes having persistent 
pain, numbness, tingling, or burning in both feet despite 
treatment.  Eligible subjects will receive two active treatment 
devices (one for each foot, to allow simultaneous treatment) and 
treat at home, twice daily for 60 days after which they will return 
to the clinic at Day 61 for a response assessment. Subjects that 
are determined to be responders at Day 61 (subjects that achieve 
a 1-point decrease in the average pain score over the last 24 hours 
using the Numeric Pain Rating Scale (NPRS)) will be 
randomized 1:1 to either active treatment or inactive sham 
devices and will continue treating through Day 120.  Subjects that 
are determined to be non-responders at Day 61 will continue 
treating with the active devices given at enrollment and will 
return to the clinic at Day 75 and Day 91 for a response 
assessment.  If a subject is determined to be a responder at Day 
75, they will be randomized 1:1 to receive either active treatment 
or inactive sham and will continue treating through Day 120.  If 
a subject is determined to be a responder at Day 91, they will be 
randomized 1:1 to receive either active treatment or sham and 
will continue to treat through Day 120.  If a subject continues to 
be a non-responder at Day 91 they will be terminated from the 
study.   
 

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Endpoints 
For this proof of concept study, the primary endpoints will be 
changes in Vibration Perception Threshold and Quantitative 
Sensory Testing between baseline and end of treatment.  
Secondary endpoints will be changes in nerve conduction 
velocity (NCV) of the sural nerve and amplitude from baseline to 
end of treatment, changes in Skin Perfusion Pressure (SPP) from 
baseline to end of treatment, change in Pain Intensity using the 
11-point Numeric Pain Rating Scale (NPRS) from baseline to end 
of treatment, change from baseline in Brief Pain Inventory (BPI) 
and Brief Fatigue Inventory (BFI), change from baseline in 
Patient Global Impression of Change (PGIC), change from 
baseline in Hospital Anxiety and Depression Scale (HADS), and 
changes from baseline in neuropathy and foot ulcer specific 
quality of life instrument (NeuroQoL). 
 
Safety will be assessed through review of Adverse Event (AE) 
reports and concomitant treatments and medications. All 
concomitant drug or non-drug treatments used during the study 
will be recorded. Safety outcomes will be assessed at the interim 
visits and the end of study visit. 
Study Procedures 
Following informed consent and assessment of eligibility, 
subjects will complete Section A-History of the Michigan 
Neuropathy Screening Instrument (MNSI) with Section B-
Physical Assessment completed by the site.  A measurement of 
the depth of the right foot will be measured from the most inferior 
aspect of the medial malleolus to the plantar aspect of the foot 
when residing on the treatment pad.  The depth should not be 
more than 8cm for eligibility.   A finger stick will be performed 
on the subject to obtain a baseline HbA1c value (A1C Now® test 
kit) and subjects will complete a Urine Drug Screen in office. 
Subjects will undergo the Ankle-Brachial Index (ABI), Venous 
Insufficiency Assessment, and Pain Phase evaluation (at least 10 
subjects in each of the 2, 3, and 4 pain phases will be enrolled).  
For subjects of child bearing potential a urine pregnancy test will 
be obtained. 
At the Enrollment Visit (can be combined with Screening), 
subjects will have a finger stick performed to collect a baseline 
glucose value.  If the Screening Visit and Enrollment Visit are 
not combined, eligibility will be re-assessed to confirm no 
changes, concomitant medications and assessments of Adverse 
Events will be obtained.  Subjects will provide their baseline pain 
score over the last 24 hours using the Numeric Pain Rating Scale 
(NPRS) and will also complete baseline health economic 
questions, questionnaires including the Brief Pain Inventory 
(BPI), Brief Fatigue Inventory (BFI), Hospital Anxiety and 
Depression Scale (HADS), and the NeuroQoL Questionnaire.  

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Vibration Perception Threshold (VPT), Quantitative Sensory 
Test (QST) and Nerve Conduction Velocity (NCV) will be 
performed. Skin Perfusion Pressure (SPP) will be performed to 
obtain a baseline value of the plantar and dorsal aspect of the right 
foot.  Eligible subjects will receive 2 active treatment devices (1 
device for each foot).  Subjects will be instructed in the use of the 
devices and will self-treat both feet twice daily (morning and 
evening; 8am ± 2 hours and 8pm ± 2 hours) for 60 days in the 
home environment. Each treatment will be 30 minutes in 
duration, treating both feet simultaneously.  Subjects will be 
provided with a study diary for capturing their daily pain scores 
based on a 11-point numerical pain rating scale (NPRS) and 
weekly Patient Global Impression of Change Score (PGIC).  
Subjects will document pain scores each day after the morning 
treatment as instructed by the site at the Enrollment Visit.  Every 
week the PGIC will be collected in the diary and the subject will 
document their overall status since the beginning of treatment. 
Subjects will either provide consent or not for biopsies to be 
obtained.  Subjects that consent to the biopsies will have two 
3mm punch skin biopsies obtained, one biopsy at the distal leg 
(10cm above the lateral malleolus) and one biopsy at the distal 
thigh (10cm above the superior margin of patella).  Biopsies will 
be taken from the right leg to represent small nerve fiber 
innervation emanating from the deep peroneal nerve. At least two 
subjects in each pain phase category (2, 3, and 4 Pain Phase) will 
be obtained. 
The site will contact the subject via telephone on Day 3 to assess 
subject adherence to treatment, completion of the diary, and any 
safety 
concerns 
and/or 
changes 
in 
concomitant 
treatments/medications.   
At Days 15 and 45, subjects will return to the clinic to have VPT 
and QST conducted and to have treatment satisfaction assessed.  
Subjects will also bring in the study devices and diary to assess 
treatment and diary compliance.  A new study diary will be 
dispensed for the next two weeks. 
At Days 30 and 61, subjects will return to the clinic to complete 
the BPI, BFI and HADS questionnaires and to have treatment 
satisfaction assessed.  VPT and QST will be conducted along 
with a finger stick to collect the subject’s blood glucose level. 
Subjects will also bring in their study devices and diary to assess 
treatment and diary compliance.  A new study diary will be 
dispensed for the next two weeks. At Day 61, SPP will be 
conducted and subjects will be assessed for a response.  If a 
subject is determined to be a responder (decrease in average pain 
score over the last 24 hours using the NPRS of at least 1 point) 

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they will return the active devices and be randomized 1:1 to 
receive active treatment or inactive sham devices and be 
instructed to treat for an additional 60 days (through Day 120).  
If the subject is determined to be a non-responder, they will 
continue treating with the active devices for an additional 15 or 
30 days and will be assessed at Day 75 and Day 91 for response. 
At Day 75, subjects will return to the clinic to have treatment 
satisfaction assessed, and have the VPT and QST conducted.  All 
subjects will bring in their devices and diary to assess treatment 
and diary compliance.  A new study diary will be dispensed for 
the next two weeks.  For those subjects determined to be non-
responders at Day 61, they will be assessed for response.  If they 
become a responder by Day 75 they will return their active 
devices and be randomized 1:1 to receive active treatment or 
inactive sham devices, and instructed to treat through Day 120.  
If the subject is still considered a non-responder, they will 
continue treating through Day 90 with the active devices given at 
Enrollment.   
At Day 91, subjects will return to the clinic to complete the BPI, 
BFI and HADS questionnaires and to have treatment satisfaction 
assessed.  The VPT and QST will be conducted along with a 
finger stick to collect the subject’s blood glucose level. Subjects 
will also bring in the study devices and diary to assess treatment 
and diary compliance.  A new study diary will be dispensed for 
the next two weeks. At Day 91, non-responders will be assessed 
for a response.  If a subject is determined to be a responder at Day 
91 (decrease in average pain score using the NPRS of at least 1 
point) they will return the active devices and be randomized 1:1 
to receive active treatment or inactive-sham devices and 
instructed to treat for an additional 30 days (through day 120).  If 
the subject is determined to be a non-responder, they will be 
terminated from the study at the end of the Day 91 visit. 
At Day 105, all subjects will have VPT and QST completed and 
have treatment satisfaction assessed.  Diaries will be collected 
and a new diary dispensed.  Subjects will also bring in the study 
devices and diary to assess treatment and diary compliance.   
At Day 121, end of study visit, subjects will have their weight, 
ABI, NCV, SPP, and Venous Insufficiency assessed.  Subjects 
will also receive a finger stick to obtain blood for the HbA1c and 
blood glucose values.  The subject will complete the BPI, BFI, 
HADS, and NeuroQoL questionnaires and have treatment 
satisfaction assessed.  The subject will return their study devices 
and diary, and the VPT and QST will be completed.  Subject’s 
that consented to having the biopsy, will have a 3mm punch skin 
biopsy obtained from the distal leg and distal thigh on the right 

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leg.  The biopsy will be obtained to represent small nerve fiber 
innervation emanating from the deep peroneal nerve. 
Assessment of adverse events and concomitant medications will 
occur at each visit. 
Study Device 
 
The study device is the PROVANT® Therapy System (PEMF). 
The active devices will deliver Pulsed Electromagnetic Field 
(PEMF) energy therapy. The active treatment and inactive sham 
devices will be identical in appearance and all other physical 
characteristics in order to maintain the blinding of the treatment. 
Each device will be identified with a unique kit number.  
Study Sample 
The anticipated enrollment in this study is up to 40 subjects. The 
study will be conducted at up to 4 sites. 
 
Primary and Secondary 
Outcome Measures 
Several efficacy outcome measures will be assessed in order to 
allow for characterization of the response to PEMF therapy. 
Efficacy Assessments 
All efficacy assessments will be conducted at the Enrollment 
Visit (Baseline; Day 0) and at the end of study visit (Day 121).  
Vibration Perception Threshold (VPT): For large nerve fiber 
assessment.  VPT is a non-invasive test used in quantifying 
sensation/sensitivity 
to 
vibration 
in 
evaluating 
sensory 
dysfunction associated with diabetic neuropathy.  The hand-held 
vibratory stimulator will be placed against the midpoint of the 
plantar aspect and big toe of the right foot, the tester will initiate 
the automated test that will last between 5-10 minutes. Three tests 
will run at each location and the average of the 3 will be 
populated by the system.  The VPT will be collected using the 
VSA-3000 Vibratory Sensory Analyzer at the midpoint on the 
plantar aspect and on the big toe of the right foot.  VPT will be 
collected at the Enrollment Visit to obtain a baseline value and 
on Days 15, 30, 45, 61, 75, 91, 105 and 121. 
Quantitative Sensory Testing (QST): For small nerve fiber 
assessment.  QST is a noninvasive test used in peripheral nervous 
system disorders for thermal sensory testing.  Contact thermal 
stimulation will be delivered using the NerveCheck Master 
through a contact thermode.  A cold test of 15°C - 25°C, heat test 
of 40°C - 46°C will be administered.  When activated the patient 
will notify the staff performing the test when they begin to feel 
the cold and warm test.  The heat and cold thermal stimulation 
will be applied over the dorsal aspect of the right foot.  QST will 
be performed at the Enrollment Visit to obtain a baseline value 
and on Days 15, 30, 45, 61, 75, 91, 105 and 121. 

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Nerve Conduction Velocity (NCV): For large myelinated nerve 
fiber assessments.  Using the NC-stat® DPNCheck®, the subject 
will assume a comfortable position so that their right leg is visible 
(that the subject’s outer ankle bone and Achilles tendon are 
visible). The patient preparation pad is then used to thoroughly 
clean the subject’s outer lower leg and ankle bone area to remove 
any residue.  The subject’s outer ankle bone is then identified to 
align the anode and cathode just behind with the cathode just 
adjacent to the middle of the ankle bone.  The device is aligned 
on the calf pressing firmly down on the foam to ensure contact.  
The sural nerve conduction velocity and amplitude will be 
recorded at the Enrollment Visit and end of study visit (Day 121). 
Skin Perfusion Pressures (SPP): Vasamed Sensilase PAD-IQ 
measures pressure (in mm Hg) of microcirculation using a laser 
Doppler sensor. Patient lies down in supine position and remains 
silent and still.  The Laser Sensor Assembly (LSA) is inserted 
into the LSA Placement Guide and the optical sensor window is 
oriented toward the skin.  For those subjects who will have 
biopsies performed, SPP will be obtained prior to the skin 
biopsies.  A cuff is positioned so that the LSA is centered on the 
bladder both horizontally and vertically. The pressure of the cuff 
is then automatically increased to a pressure necessary to occlude 
blood flow and then released at a controlled rate and a 
measurement of the pressure in the angiosome is made. SPP 
(mmHg) at reactive hyperemia is recorded.  A second measure of 
SPP will be obtained on the plantar aspect of the right foot 
directly below the location where the SPP was performed on the 
dorsal aspect of the right foot.  SPP will be conducted at the 
Enrollment Visit, Day 61, and end of study visit (Day 121). 
Pain Intensity (PI): a validated 11-point Numeric Pain Rating 
Scale (NPRS) with scores (0-10) collected as patient-reported 
outcomes on a paper diary and at the Enrollment visit to obtain a 
baseline value and on Days 61, 75, and 91 to determine response. 
On the patient diary, PI will be assessed after each morning (8am 
± 2 hours) treatment.  Subjects will report their average pain score 
over the last 24 hours.  Diaries will be distributed and collected 
from the subjects every 2 weeks to ensure compliance.   
Brief Pain Inventory (BPI): is a 32-question long form 
questionnaire that assesses the severity of pain and its impact on 
specific daily functions.  Cronbach’s alpha reliability ranges from 
0.77-0.91. The BPI long form will be administered at the 
Enrollment Visit, Day 30, 61, 91, and end of study visit (Day 
121). 
Brief Fatigue Inventory (BFI): is a 4-question assessment that 
assesses the level of fatigue and the impact of the fatigue on daily 

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function over the last 24 hours.  A global fatigue score is 
collected by averaging all items on the BFI. Cronbach’s alpha 
reliability ranges from 0.82-0.97. BFI is patient reported and 
collected at the Enrollment Visit, Days 30, 61, 91, and end of 
study visit (Day 121). 
Patient Global Impression of Change (PGIC): a 7-point 
validated categorical scale of overall change in status since 
initiation of treatment with the study device. PGIC allows 
subjects to integrate, into one overall evaluation, the different 
aspects of their response to treatment, including pain reduction, 
improvement in functioning and side effects. PGIC will be 
collected every 7 days in the paper diary, immediately following 
the morning treatment.  PGIC serves to anchor within-subject 
changes in pain over the course of treatment. 
 
Hospital Anxiety and Depression Scale (HADS): is a patient 
reported assessment that detects stats of depression and anxiety.  
The subscales within the assessment assess the severity of the 
emotional disorder connected to having diabetic peripheral 
neuropathy.  Subjects will complete the assessment at the 
Enrollment Visit, Days 30, 61, 91, and end of study visit (Day 
121). 
NeuroQoL: is a validated assessment that measures the effects 
of diabetic peripheral neuropathy and its complications on an 
individual’s quality of life. The questionnaire will be completed 
by the subject at the Enrollment Visit and end of study visit (Day 
121). 
 
Experimental Outcome Assessment 
Skin Biopsy: To assess c-fiber nerve density.  Subjects that 
provide consent to having biopsies taken will have two 3mm 
punch skin biopsies obtained, one biopsy at the distal leg (10cm 
above the lateral malleolus) and one biopsy at the distal thigh 
(10cm above the superior margin of patella) on the right leg at 
the Enrollment Visit.  At least 2 subjects in each pain phase 
category (2, 3, and 4 Pain Phase) will have a biopsy obtained. 
The biopsy will be shipped overnight to the central lab for 
processing.  At the Day 121 Visit, a second set of biopsies will 
be obtained to the right of each prior biopsy on the distal leg and 
distal thigh of the right leg.  The samples will be shipped 
overnight to the central lab for processing.  The lab will assess 
the samples for nerve fiber density and compare to baseline. 
Statistical Considerations 
This bi-phasic design includes 2 sequential periods: the Induction 
Phase and Randomized Withdraw Phase.  All safety analyses will 

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be performed on the safety analysis set, defined as all subjects 
who were enrolled into the study and issued study devices during 
the Induction Phase and followed through the Randomized 
Withdraw Phase.  Once the subject is determined to be eligible, 
the subject will be issued active treatment devices and the subject 
will be formally enrolled into the study and become part of the 
Safety Analysis Set. 
  
All recorded data will be listed by subject and time point.   
Descriptive statistics will be tabulated for all randomized 
subjects for the change from baseline to study day 120 
(Completers Analysis Set), and separately for the change from 
baseline to the last recorded set of evaluations (End of Study 
Evaluation Set).  This latter set should include all subjects who 
were randomized and complete at least one set of evaluations 
after randomization. 
 
Treatment-emergent adverse events will be summarized by type, 
frequency, severity, and relationship to the study device.  
Adverse events will be provided in a listing. 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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I. 
INTRODUCTION AND BACKGROUND ................................................................................... 17 
II. 
STUDY OBJECTIVES ............................................................................................................. 23 
III. 
STUDY DESIGN ................................................................................................................... 24 
A. 
STUDY DESIGN ................................................................................................................................. 24 
B. 
EFFICACY ENDPOINTS ........................................................................................................................ 26 
C. 
SAFETY EVALUATION ......................................................................................................................... 26 
D. 
ELIGIBILITY CRITERIA .......................................................................................................................... 26 
1. 
Inclusion Criteria ........................................................................................................................... 26 
2. 
Exclusion Criteria .......................................................................................................................... 27 
E. 
RECRUITMENT .................................................................................................................................. 29 
F. 
RANDOMIZATION .............................................................................................................................. 29 
G. 
DEVICE DESCRIPTION ......................................................................................................................... 29 
1. 
Control Unit .................................................................................................................................. 29 
2. 
Disposable Applicator Covers. ...................................................................................................... 30 
3. 
Treatment Applicator ................................................................................................................... 30 
H. 
LOGISTICS AND DEVICE ACCOUNTABILITY .............................................................................................. 31 
I. 
LABELING ........................................................................................................................................ 31 
J. 
PREPARATION AND ADMINISTRATION ................................................................................................... 32 
K. 
BLINDING ........................................................................................................................................ 32 
L. 
STUDY ASSESSMENTS ........................................................................................................................ 32 
1. 
Primary Efficacy Assessments ...................................................................................................... 33 
2. 
Secondary Efficacy Assessment .................................................................................................... 33 
3. 
Exploratory Efficacy Assessment .................................................................................................. 35 
4. 
Additional Study Assessments ...................................................................................................... 35 
5. 
Safety Assessments ...................................................................................................................... 37 
IV. 
STUDY PROCEDURES .......................................................................................................... 37 
A. 
VISIT 1 – SCREENING VISIT (DAY -14 TO 0) ........................................................................................... 37 
B. 
VISIT 2 – ENROLLMENT VISIT (DAY 0) .................................................................................................. 38 
C. 
DAY 3 PHONE CALL (DAY 3 +2 DAYS) .................................................................................................. 39 
D. 
DAY 15 INTERIM VISIT (DAY 15 + 3 DAYS) ........................................................................................... 39 
E. 
DAY 30 INTERIM VISIT (DAY 30 + 3 DAYS) ........................................................................................... 39 
F. 
DAY 45 INTERIM VISIT (DAY 45 + 3 DAYS) ........................................................................................... 40 
G. 
DAY 61 VISIT (DAY 61 +3 DAYS)......................................................................................................... 40 
H. 
DAY 75 INTERIM VISIT (DAY 75 + 3 DAYS) ........................................................................................... 41 
I. 
DAY 91 VISIT (DAY 91 +3 DAYS)......................................................................................................... 41 
J. 
DAY 105 INTERIM VISIT (DAY 105 + 3 DAYS) ....................................................................................... 42 
K. 
DAY 121 VISIT (DAY 121 + 3 DAYS) .................................................................................................... 42 
L. 
TREATMENT ADHERENCE/STUDY COMPLIANCE ....................................................................................... 43 
M. 
PROTOCOL ADHERENCE ..................................................................................................................... 43 
N. 
CONCOMITANT MEDICATIONS ............................................................................................................ 43 

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1. 
Allowed Medications .................................................................................................................... 44 
2. 
Prohibited Medications/Treatments ............................................................................................ 44 
V. 
WITHDRAWAL PROCEDURES............................................................................................... 45 
VI. 
STATISTICAL CONSIDERATIONS ........................................................................................... 45 
A. 
INDUCTION PHASE / BASELINE EVALUATIONS ........................................................................................ 45 
B. 
RANDOMIZED WITHDRAW PHASE ........................................................................................................ 46 
C. 
SUMMARIZATION OF RESULTS ............................................................................................................. 46 
D. 
ADVERSE EVENTS .............................................................................................................................. 47 
E. 
SAMPLE SIZE .................................................................................................................................... 47 
VII. 
INFORMED CONSENT .......................................................................................................... 47 
VIII. 
INSTITUTIONAL REVIEW BOARD.......................................................................................... 48 
IX. 
TERMINATION OF THE INVESTIGATION ............................................................................... 48 
X. 
ADVERSE EVENTS AND UNANTICIPATED ADVERSE DEVICE EFFECTS ...................................... 48 
A. 
ADVERSE EVENTS .............................................................................................................................. 48 
B. 
ANTICIPATED ADVERSE DEVICE EFFECTS ASSOCIATED WITH PROVANT THERAPY SYSTEM .............................. 50 
C. 
UNANTICIPATED ADVERSE DEVICE EFFECT (UADE) ................................................................................ 51 
XI. 
INVESTIGATOR’S FILES/RETENTION OF DOCUMENTS ........................................................... 51 
A. 
SOURCE DOCUMENTS AND BACKGROUND DATA .................................................................................... 52 
B. 
AUDITS AND INSPECTIONS .................................................................................................................. 52 
XII. 
MONITORING THE STUDY ................................................................................................... 52 
XIII. 
CONFIDENTIALITY OF TRIAL DOCUMENTS AND SUBJECT RECORDS ....................................... 52 
XIV. 
PUBLICATION OF DATA AND PROTECTION OF TRADE SECRETS ............................................. 53 
XV. 
REFERENCES ....................................................................................................................... 54 
APPENDIX A - TIME AND EVENTS SCHEDULE ....................................................................................... 57 
APPENDIX B - PAIN PHASE ASSESSMENT SCALE .................................................................................. 59 
APPENDIX C – SUBJECT DIARY FOR DAILY PAIN SCORE AND WEEKLY GLOBAL IMPRESSION OF CHANGE
 
60 
APPENDIX D – INSTRUCTIONS FOR OBTAINING ANKLE-BRACHIAL INDEX ............................................. 61 
APPENDIX E – GRADING SYSTEM FOR VENOUS INSUFFICIENCY ........................................................... 63 
 
 
 

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LIST OF ABBREVIATIONS 
ABI 
 
Ankle Brachial Index 
AE 
 
Adverse Event 
AGE  
Advanced Glycation End Products 
BFI 
 
Brief Fatigue Inventory 
BPI 
 
Brief Pain Inventory 
CBT 
 
Cognitive Behavioral Therapy 
CFR   
Code of Federal Regulations 
CRA   
Clinical Research Assistant / Associate 
DAC  
Disposable Applicator Cover 
DFU  
Diabetic Foot Ulcerations 
DPN  
Diabetic Peripheral Neuropathy 
DTR  
Deep Tendon Reflexes 
DSPN   
Distal Symmetric Sensorimotor Polyneuropathy 
E-STIM 
Electrical Nerve Stimulation 
FCC 
 
Federal Communication Commission 
FDA  
Food & Drug Administration 
HADS  
Hospital Anxiety and Depression Scale 
HIV 
 
Human Immunodeficiency Virus 
IRB 
 
Institutional Review Board 
LOPS  
Loss of the Protective Sensation 
LSA 
 
Laser Sensor Assembly 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCV  
Nerve Conduction Velocity 
NeuroQoL 
Neuropathy and foot ulcer specific quality of life instrument 
NOS  
Nitric Oxide Synthase 
NPRS  
Numeric Pain Rating Scale 
PEMF  
Pulsed Electromagnetic Field 
PGIC  
Patient Global Impression of Change 
POC  
Proof of Concept 
PRFE  
Pulsed Radio Frequency Energy 
PRN  
As Needed 

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PT 
 
Physical Therapy 
QA  
 
Quality Assurance 
QC  
 
Quality Control 
SAE   
Serious Adverse Event 
SAP   
Statistical Analysis Plan 
SAS 
 
Statistical Analysis System 
SPP 
 
Skin Perfusion Pressure 
SSRI  
Selective Serotonin Reuptake Inhibitors 
TCA  
Tricyclic Antidepressants 
QST 
 
Quantitative Sensory Test 
VPT 
 
Vibration Perception Threshold 

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I. 
INTRODUCTION AND BACKGROUND 
The Centers for Disease Control and Prevention (CDC) has estimated the number of diagnosed and 
undiagnosed level of diabetes mellitus to be 29.1 million people or 9.3% of the United States 
population.1  The most common form of diabetes mellitus, type 2 diabetes mellitus, is projected to 
affect an estimated 366 million people worldwide by 2030.2  About 60 to 70 percent of individuals 
diagnosed with type 1 or type 2 diabetes mellitus have some form of diabetic neuropathy ensuing 
from hyperglycemic-induced metabolic abnormalities.  As such, diabetic neuropathy is major cause 
of morbidity in patients with diabetes mellitus.  While symptomatic or asymptomatic neuropathy 
can be diagnosed at any time during disease course there tends to be an increased association with 
increased age and longer duration of diabetes.3 The highest rates of neuropathy are found in 
individuals diagnosed with diabetes for at least 25 years or greater and there has been an association 
with hypertension and obesity.  Acute, aggressive glycemic control has been associated with 
improvement in the severity of neuropathy.  Nonetheless, the sine qua non for the development and 
severity of diabetic neuropathy is chronic poor glycemic control.3, 4, 5  
Clinical neuropathy syndromes associated with diabetes mellitus are categorized according to 
their neurologic distribution.  While overlap in presentation exists the categories are as follows: (5)   
                           Table 1—Classification for Diabetic Neuropathies 
A.  Diffuse neuropathy 
Distal Sensorimotor Peripheral Neuropathy 
(DSPN) 
 Primarily small-fiber neuropathy 
 Primarily large-fiber neuropathy 
 Mixed small- and large-fiber neuropathy 
(most common) 
Autonomic Neuropathy   
 Cardiovascular Neuropathy (CAN) 
 Reduced HRV 
 Resting tachycardia 
 Orthostatic hypotension 
 Sudden death (malignant arrhythmia) 
 Gastrointestinal 
 Diabetic gastroparesis (gastropathy) 
 Diabetic enteropathy (diarrhea) 
 Colonic hypomotility (constipation) 
Urogenital 
 Diabetic cystopathy (neurogenic bladder) 
 Erectile dysfunction 
 Female sexual dysfunction 
Sudomotor Dysfunction 
 Distal hypohydrosis/anhidrosis, 
 Gustatory sweating 
Hypoglycemia Unawareness 
Abnormal Pupillary Function 
B. Mononeuropathy (mononeuritis multiplex) (atypical forms) 
 Isolated cranial or peripheral nerve (e.g., CN III, ulnar, median, 
femoral, peroneal) 
 Mononeuritis multiplex (if confluent may resemble 
polyneuropathy) 
C. Radiculopathy or polyradiculopathy (atypical forms) 
 Radiculoplexus neuropathy (a.k.a. lumbosacral 
polyradiculopathy, proximal motor amyotrophy) 
 Thoracic radiculopathy 
 
Nondiabetic neuropathies common in diabetes 
 Pressure palsies 
 Chronic inflammatory demyelinating polyneuropathy 
 Radiculoplexus neuropathy 
 Acute painful small-fiber neuropathies (treatment-induced) 

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Distal symmetric sensorimotor polyneuropathy (DSPN) is the most common form of diabetic 
neuropathy and accounts for approximately half of the diabetic-related neuropathy diagnosed in the 
US.  Clinical presentation and clinical course of diabetic neuropathy varies in prevalence associated 
with both the duration of disease and maintenance of adequate glycemic control.  Corresponding to 
length dependent nerve damage, patients present with distal symptoms that progress proximately 
affecting the lower extremities more prominently than upper extremities.  Patients typically 
describe DSPN symptoms in terms of increased or decreased sensations resulting from damage of 
the myelinated and unmyelinated cutaneous nerve fibers.   
Clinical Presentation of Distal Symmetric Sensorimotor Polyneuropathy (DSPN) initially 
involves the feet and hands.  DSPN initially affects smaller unmyelinated C-fibers which convey 
light touch, pain and temperature with subsequent progression to involve larger myelinated A delta-
fibers which convey vibratory sensation, proprioception and joint position.  As the disease 
progresses motor function becomes impaired.  Early in the process this may require nerve 
conduction velocity testing and assessment of reduced deep tendon reflexes (DTR) for detection 
prior to the development of noticeable weakness on flexion or extension of digits.  Progressively 
severe disease may demonstrate weakness with foot and ankle dorsiflexion and extension and grip 
strength. 4,5,6 
Management of Peripheral Diabetic Neuropathy 5 
(Adapted Bolton 2005) 
 
Increased (Painful) 
Decreased (Painless) 
Burning pain 
Asleep 
Knife-like 
“Dead” 
Electrical sensations 
Numbness 
Squeezing 
 
Tingling 
 
Constricting 
 
Prickling 
 
Hurting 
 
Freezing 
 
 
Microvascular compromise of smaller arterioles demonstrating endothelial dysfunction progressing 
to calcification and dysfunction in larger vasculature add to the complexity of the medical 
presentation with overlapping syndromes of peripheral ischemia that may or may not contribute to 
the lower extremity pain experienced by patients.  Diabetic-related metabolic abnormalities lead to 
an impaired immune response to infection and the effect of diabetes on bones, cartilage, tendons 
and fascial tissue causes mechanical and conformational changes in the architecture of the foot.  
Gait abnormalities, impaired balance and falls frequently ensue.  In advanced peripheral diabetic 
neuropathy, the patient no longer senses pain developing a loss of the protective sensation (LOPS), 
the most common component in the pathway to the development of diabetic foot ulcerations (DFU) 
and for the development of Charcot’s neuroarthropathy.5.6,9  Combined with ischemia and infection, 

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LOPS frequently culminates in amputation.  DFUs are responsible for more hospitalizations than 
any other complication of diabetes with 5% of diabetic patients developing foot ulcers in the U.S. 
each year and 1% of those patients requiring an amputation.7 
Pathophysiology for DSPN, as noted above, is complex and involves multiple mechanistic 
pathways.  Currently, a combination of direct and indirect axonal injury.  Hyperglycemia in concert 
with insulin resistance and abnormal adiposity leads to the accumulation of advanced glycation end 
products (AGE), toxic effects of free fatty acids and pro-inflammatory adipokines.  These factors 
damage nerve fibers, effecting initially smaller unmyelinated C-fibers and progressively advancing 
to damage larger myelinated fibers.  Direct axonal injury occurs secondary to endothelial injury 
causing endothelial dysfunction, nitric oxide synthase (NOS) levels are reduced leading to small 
vascular vasoconstriction, larger vascular calcifications and constriction, which ultimately result in 
nerve ischemia.5,6,7     
Therapeutic Intervention for the prevention and treatment of distal symmetric sensorimotor 
polyneuropathy (DSPN) are generally related to counselling, antioxidant-rich nutrition, optimized 
glycemic control, weight management, moderate exercise, routine foot screening and proper foot 
wear, and avoidance of alcohol and tobacco.  Care must be taken to ensure nondiabetic causes of 
neuropathy have been assessed and excluded- hereditary, malignant disease (e.g., bronchogenic 
carcinoma), metabolic disorders (e.g., thyroid, renal disease), toxic (e.g., alcohol), infective agents 
(e.g., Human Immunodeficiency Virus (HIV), Lyme’s, Hepatitis B infection), vitamin B 
deficiencies (e.g., B1, B6, B12, tocopherol), iatrogenic interventions (e.g., isoniazid, vinca 
alkaloids, amiodarone, colchicine, Dapsone, Taxol), heavy metals (e.g., mercury, arsenic), and 
medication-related (chemotherapy, HIV treatment).(4.5)  Nonetheless, aside from adequate glycemic 
control and antioxidants, medical therapies for improving impaired nerve function have been 
lacking and the focus of diabetic neuropathy management has focused predominantly on 
pharmaceutical-based pain control.  The wide variety of medical classifications represented reflect 
the diffuse nature of the disorder and the lack of specificity for improvement across the population 
of patients being treated.  For patients who require pharmacologic treatment, first-line therapies 
include tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin-
norepinephrine reuptake inhibitors (SNRI), and anticonvulsants, specifically those which increase 
the availability of gamma-aminobutyric acid. 
Modified Drug Class Drug Daily Dose (mg) Side Effects 4,5,9 
Category 
Agent 
Daily Dosage 
Side Effects 
Tricyclics 
Amitriptyline  
Imipramine  
Doxepine 
25–150 mg 
25–150 mg 
10 mg 
++++ 
++++ 
+++ 
SSRIs 
Paroxitene  
Citalopram  
40 mg 
40 mg 
+++ 
+++ 
Anticonvulsant 
Agents 
Gabapentin  
900–1,800 mg 
++ 
Pregabalin  
Lamotrigine  
160–600 mg 
200–400 mg 
++ 
++ 

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Carbamazepine  
up to 800 mg 
+++ 
SNRI 
Duloxetine 
60 mg  
+++ 
Anti-arrhythmic 
Agents 
Mexilitene  
up to 450 mg 
+++ 
Opioids 
Tramadol  
Oxycodone CR 
50–400 mg  
10–60 mg 
+++ 
++++ 
 
While tricyclic antidepressants are the most studied agents used for neuropathic pain, physicians 
have been using TCAs, such as amitriptyline and nortriptyline (Pamelor), to treat neuropathic pain 
for years without approved labeling from the U.S. Food and Drug Administration (FDA).  
Duloxetine (Cymbalta®) and pregabalin (Lyrica®) are the only agents approved by the FDA 
specifically for the treatment of painful peripheral diabetic neuropathy. Patients frequently 
supplement oral agents with topical therapy- including capsaicin 0.075% cream, doxepin 5% 
solution or lidocaine 5% patches.  Additionally, topical nitrates, alpha-lipoic acid antioxidant, and 
homeopathic agents such as evening primrose oil have been reported with variable success in 
reducing neuropathic pain.  Opioids are generally prescribed for severe, unresponsive pain. 
In an effort to avoid overuse of opioids for severe unrelenting pain, the American Pain Society and 
the Academy of Pain Medicine have generated guidelines that include the use of non-
pharmaceutical interventions currently used to treat chronic pain, Clinical Guidelines for the Use 
of Chronic Opioid Therapy in Chronic Noncancer Pain.  Non-pharmaceutical agents such as 
electrical nerve stimulation (E-Stim), acupuncture, electro-acupuncture, cognitive behavioral 
therapy (CBT), biofeedback, and physical therapy (PT) have some usefulness in treating painful 
peripheral DSPN.10 
Trial:  This proof-of-concept (POC) trial is being conducted to evaluate the therapeutic value of 
using pulsed electromagnetic energy fields (PEMF) in the treatment of diabetic neuropathy.   
Study Product:  PROVANT® Therapy System 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 in 
superficial 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® Therapy System 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 the device since 2004 and has treated over 10,000 patients within the U.S.  Over 
two million individual treatments have been administered with rare adverse events reported. [FDA 

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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 PEMF 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 
findings suggest that PEMF therapy reduces pain both by modulating inflammation and by 
activating peripheral endogenous opioids. 
An exploratory prospective randomized, sham-controlled IRB-approved study was recently 
conducted at two sites using the PROVANT® Therapy System to evaluate small fiber nerve growth 
and function in subjects with painful peripheral diabetic neuropathy. Twenty-three subjects with 
painful peripheral diabetic neuropathy were treated for 60 days with twice-daily PEMF therapy. 
Subjects were eligible for enrollment if they had type 2 diabetes having persistent numbness, 
tingling, or burning in at least one foot despite standard of care treatment.  
Eighteen subjects in this study were evaluated for the effectiveness of the PROVANT® Therapy 
System in enhancing small fiber nerve growth and function.  PEMF treatment twice daily for 60 
days was associated with improved skin perfusion pressure, and improved nerve conduction.   
The purpose of the current study is to further elucidate the underlying mechanisms of increased 
sensation and pain relief observed in patients receiving treatment with the PROVANT® Therapy 
System.   In vitro studies have provided evidence that PEMF therapy improves nerve growth and 
may improve nerve function through up-regulation of genes involved in neurogenesis. [Data on 
File] In addition, genes related to angiogenesis have also been shown to be up-regulated.  Through 
evaluation of vibration perception threshold, nerve conduction velocity, quantitative sensory 
testing, vascular changes (skin perfusion pressure), blood glucose (hemoglobin A1c), and quality 

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of life questionnaires, this study will evaluate if PEMF treatment in vibration perception and skin 
perfusion is enhanced in subjects that receive treatment with Provant compared to a group of 
subjects that receive treatment with a sham device.   
 
 
 
 
 
 
 

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II. 
STUDY OBJECTIVES  
This study is designed to evaluate the effectiveness of the PROVANT® Therapy System 
(PEMF) in changing Vibration Perception Threshold (VPT) and Thermal Sensory 
Perception using Quantitative Sensory Testing (QST) in patients with bilateral symmetrical 
diabetic peripheral neuropathy (DPN) when treatment is administered twice daily through 
a 120-day period. 

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III. 
STUDY DESIGN 
A. 
Study Design 
The study is a multi-center, sham-controlled, double-blind, enriched enrollment randomized 
withdrawal study of the safety and efficacy of multi-dose PEMF therapy on subjects with 
bilateral symmetrical DPN.  A graphic presentation of the study design is shown in Figure 
1. 
Figure 1.  
Study Flow Schematic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment Visit (Day 0) 
Baseline assessments and Active device dispensing 
3-Day Follow-Up Phone Call (Day 3 + 2 days) 
Assess subject adherence, safety, and concomitant medications 
Day 15 Interim Visit (Day 15 +3 days) 
Assess subject adherence, safety, DPN Assessments and concomitant medications 
Screening Visit (Day -14 to Day 0) 
To assess eligibility 
Day 30 Interim Visit (Day 30 +3 days) 
Assess subject adherence, safety, DPN Assessments and concomitant medications 
Day 45 Interim Visit (Day 45 +3 days) 
Assess subject adherence, safety, DPN Assessments and concomitant medications 

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Day 61 Interim Visit (Day 61 +3 days) 
Assess subject adherence, safety, DPN Assessments, concomitant medications, and response assessment 
Responder 
Non-Responder 
Randomize (1:1) Active or Sham 
Continue Active Treatment 
Day 75 Interim Visit (Day 75 +3 days) 
Assess subject adherence, safety, DPN 
Assessments and concomitant medications 
Day 75 Interim Visit (Day 75 +3 days) 
Response assessment, subject adherence, safety, 
DPN Assessments and concomitant medications 
Responder 
Randomize (1:1)  
Non-Responder 
Continue Active Treatment 
Day 91 Interim Visit (Day 91 +3 days) 
Assess subject adherence, safety, DPN 
Assessments and concomitant medications 
Day 91 Interim Visit (Day 91 +3 days) 
Response assessment, subject adherence, safety, 
DPN Assessments and concomitant medications 
Responder 
Randomize (1:1)  
Non-Responder 
Terminate 
Day 105 Interim Visit (Day 105 +3 days) 
Assess subject adherence, safety, DPN 
Assessments and concomitant medications 
Day 121 End of Study Visit (Day 121 +3 days) 
Assess subject adherence, safety, DPN Assessments and 
concomitant medications 

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B. 
Efficacy Endpoints  
This study will evaluate the changes in vibration perception threshold, thermal sensory 
perception, nerve conduction velocity, skin perfusion pressure, pain intensity, brief pain 
inventory, brief fatigue inventory, PGIC, hospital anxiety and depression scale, and 
neuropathy specific quality of life. 
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 study 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 during the treatment period by treatment assignment.  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 and less than 80 years of age. 
 
2. Subject has documented Type 1 or Type 2 diabetes mellitus (receiving insulin, diet 
controlled, or taking parenteral hypoglycemic agents) 
 
3. Subject is on a stable antidiabetic regimen (medication and/or diet) to control their 
diabetes for at least 30 days prior to Screening. 
 
4. Subject has an HbA1c <10% at Screening or within 2 months of Screening. 
 
5. Subject has daily pain attributed to bilateral symmetrical Diabetic Peripheral 
Neuropathy with numbness, tingling, and/or burning based on clinical judgement for at 
least 6 months prior to screening. 
 
6. Subject’s pain or discomfort from DPN is identifiable. 

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7. Subject is in pain Phase 2, 3, or 4 as per the Phasing of Neuropathy Scale. 
 
8. Subjects average pain over the last 24 hours is ≥3 based on the 11-point Numeric Pain 
Rating Scale (NPRS) at the Screening Visit. 
 
9. Subject has adequate lower extremity pulse in both feet and no intermittent claudication. 
 
10. Subject is able to ambulate independently with assistive devices, but not wheel chair 
bound. 
 
11. Subject is willing and able to give written informed consent and to comply with all parts 
of the study protocol. 
 
12. Female subjects must be post-menopausal, surgically sterile, abstinent, or practicing (or 
agrees 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 is in pain Phase 1 or 5 as per the Phasing of Neuropathy Scale. 
2. Subject has an active, open ulcer on the lower extremities. 
3. Subject has peripheral vascular disease defined as absence of more than one foot pulse 
per foot and/or ABI <0.8 and >1.4 and/or history of angioplasty or peripheral bypass 
surgery within 6 months of the Screening Visit.   
4. Subject has venous insufficiency as classified by the Venous Insufficiency 
Classification System of grade C6. 
5. Subject has undergone nerve decompression surgery on the lower extremities. 
6. Subject has a history of previous kidney, pancreas, cardiac transplantation, or severe 
renal disease. 
7. Subject has been diagnosed with non-diabetic chronic inflammatory neuropathic disease 
(e.g. end stage renal disease, hepatitis C, chemotherapy induced neuropathy, known 
connective tissue disease, systemic lupus). 
8. Subject has peripheral vascular disease requiring revascularization of lower limb or 
amputation or evidence of ulcer amputation. 

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9. Subject has clinically significant cardiovascular disease within 6 months prior to 
screening (unstable or poorly controlled hypertension, transient ischemic attack, MI, 
unstable angina, arrhythmia, any heart surgery, stent placement, heart disease). 
10. Subject has a history of any uncontrolled medical illness that in the Investigators 
judgment places the subject at unacceptable risk for receipt of PEMF therapy. 
11. Subject requires or anticipates the need for surgery of any type or travel during the 
treatment period. 
12. Subject has a total foot depth (most inferior aspect of the medial malleolus to the plantar 
aspect of the foot when residing on a treatment pad) of >8 cm. 
13. Subject has received any investigational drug or device within 30 days prior to the 
Screening Visit or within 6 weeks prior to the Screening Visit for long acting lidocaine 
injection products. 
14. Subject has used systemic corticosteroids within 3 months of the Screening Visit. 
15. Subject has a history of malignancy within the past 5 years other than successfully 
treated non-metastatic basal cell or squamous cell carcinomas of the skin in the treatment 
area and/or localized in situ carcinoma of the cervix. 
16. Subject has a serious psychosocial co-morbidity. 
17. Subject has a history of drug or alcohol abuse, as confirmed by urine drug screen, within 
one year prior to the Screening Visit. 
18. Subject has an implanted pacemaker, defibrillator, neurostimulator, spinal cord 
stimulator, bone stimulator, cochlear implant, or other implanted device with an 
implanted metal lead(s). 
19. Subject is currently pregnant or planning on becoming pregnant prior to Day 121. 
20. Subject has previously treated with PROVANT® Therapy System within 60 days on the 
lower extremity. 
21. Subject is unwilling or unable to follow study instructions or comply with the treatment 
regimen, diary documentation, and study visits. 
22. Subject has pain from any other source that can confuse the assessment of the pain 
associated with DPN. 
23. Subject has a clinically significant foot deformity (Charcot’s syndrome or club foot). 

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24. Subject has received nerve blocks for neuropathic pain within 4 weeks of the Screening 
Visit. 
25. Subject has been diagnosed with mononeuropathy. 
26. Subject has a skin condition that could alter their sensation. 
27. Subject has had a previous surgery to the spine or lower extremity with residual 
symptoms of pain or difficulty with movement. 
28. Subject has moderate or severe arthropathy (RA, OA, Gout) that causes discomfort 
during casual walking or stair climbing. 
E. 
Recruitment  
Recruitment for study subjects will be drawn from the patient population at the investigative 
study site. Recruitment efforts will be supplemented with IRB approved internet, radio 
and/or print advertising as necessary.  
F. 
Randomization 
The schedule for randomization of subjects and allocation to treatment will be prepared 
using SAS® (Statistical Analysis System; Cary, NC) to create a computer-generated scheme 
based on a permuted block algorithm. The randomization schedule will randomize in a 1:1 
ratio (active : sham) to a device based on the randomization kit numbers. The kit numbers 
will be assigned sequentially to subjects that qualify for inclusion into the study.  
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 
(FCC) authorized medical device frequency of 27.12 MHz.  The primary components are 
the control unit, the treatment applicator that generates and delivers the shortwave RF 
energy, and single-use Disposable Applicator Covers (DACs) 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 
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 

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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.   
In this study, the subject will treat both feet for 30 minutes, twice a day for the first 60 
days (and up to 90 days) with active devices, and then continue to treat after 
randomization until Day 120. Response to treatment for randomization will be assessed 
at Days 61, 75, or 91.  
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 PEMF 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 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 PEMF 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   
The PEMF system delivers pulsed RF energy to the desired treatment area via a spiral 
antenna in the treatment applicator.  The treatment applicator 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 

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treatment applicator 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 randomized to active treatment 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 circuit board for the preset 30-minute 
duration of therapy.  
The amount of forward RF energy emitted from the treatment applicator is preset at 591 
± 44 V/m at a distance of 5.0 cm from the radiating surface of the treatment applicator.  
The amount of radiated RF energy diminishes with increasing distance from the 
radiating surface of the treatment applicator.  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 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 Instruction Manual 
which accompanies the study device, and if unsuccessful in resolving the matter, will 
contact the sponsor to access a replacement device.   
H. 
Logistics and Device Accountability 
 
The study devices will be shipped via courier (FedEx) delivery or hand delivered when 
possible to the investigator or designee at regular intervals or as needed during the study.  
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 site study coordinator or other delegated 
staff member. These records should contain the dates, quantities of device received by the 
investigator, dispensed to specified subjects, or returned to sponsor. 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 label on each study device kit will contain the protocol number and kit number. There 
will be sufficient space for study personnel to write the subject number, date dispensed, and 
the initials of the dispenser on the distribution label. 

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J. 
Preparation and Administration  
Each subject will receive two devices to use during the study. Each treatment session with 
the study devices will be 30 minutes in duration.  All treatment sessions will be self-
administered by the subject or his/her family or caregiver in the home or similar setting. 
The first treatment with the study devices will be administered on the morning of the day 
following the Enrollment Visit (Day 1) at 8am (+ 2 hours). Subjects will assume a 
comfortable position and place their feet (both feet will be treated) on the treatment 
applicators of the PEMF devices, centering the applicators under the plantar surface (bottom 
of foot) of each foot as identified by the investigator. Treatment will be administered 
continuously for 30 minutes on both feet simultaneously. Thereafter, subjects will self-
administer treatments twice daily, at 8am (± 2 hours) and 8pm (± 2 hours) up to Day 120 
(Day 91 for non-responders).  
Prior to initiation of each treatment session, the subject will take the treatment applicator of 
each study device and insert it into a new Disposable Applicator Cover. When inserted 
properly, the yellow starburst logo on the treatment applicator 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 
subject’s feet, the side of the treatment applicator with the yellow starburst logo is directed 
toward the bottom of the foot (plantar surface).  Further directions for use for the PEMF 
system are found in the Instruction Manual.  Upon completion of the treatment session, the 
subject will remove and discard the Disposable Applicator Covers, and store the PEMF 
devices until the time of the next scheduled treatment session.  Disposable Applicator 
Covers may be discarded as standard waste. 
K. 
Blinding 
At the start of this study, all subjects will receive active devices.  At Day 61, Day 75, or Day 
91, if the subject becomes a responder based on a 1-point decrease in the average pain score 
using the Numeric Pain Rating Scale, the subject will be randomized 1:1 (active: sham). 
The sham devices will be PEMF devices that are de-activated such that no radiofrequency 
energy is generated or delivered when the device is started. All other functions, including 
the start sequence, display lights, audible start-beep and fan operation of the sham devices 
are identical to that of the active PEMF devices. Sham devices are indistinguishable from 
the active PEMF devices being used in the study.  The subjects, research personnel at the 
investigative site, and sponsor will be fully blinded to the randomization assignment and 
unable to differentiate active and sham devices.   
L. 
Study Assessments 
All efficacy outcome measures will be assessed in order to allow for characterization of the 
response to PEMF therapy. All efficacy assessments will be conducted at the Enrollment 
Visit (Baseline; Day 0) and at the end of study visit (Day 121). 

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1. Primary Efficacy Assessments 
Vibratory Perception Threshold (VPT):  For large nerve fiber assessment.  VPT is a 
non-invasive test used in quantifying sensation/sensitivity to vibration in evaluating 
sensory dysfunction associated with diabetic neuropathy.  The hand-held vibratory 
stimulator will be placed against the midpoint of the plantar aspect and big toe of the right 
foot; the tester will initiate the automated test that will last between 5-10 minutes. Three 
tests will run at each location and the average of the 3 will be populated by the system.  
The VPT will be collected using the VSA-3000 Vibratory Sensory Analyzer at the 
midpoint on the plantar aspect and on the big toe of the right foot.  VPT will be collected 
at the Enrollment Visit to obtain a baseline value and on Days 15, 30, 45, 61, 75, 91, 105 
and 121.   
Quantitative Sensory Testing (QST): For small nerve fiber assessment.  QST is a 
noninvasive test used in peripheral nervous system disorders for thermal sensory testing.  
Contact thermal stimulator will be delivered using the NerveCheck Master through a 
contact thermode.  A cold test of 15°C - 25°C and heat test of 40°C - 46°C will be 
administered.  When activated the patient will notify the staff performing the test when 
they begin to feel the cold and warm test.  The heat and cold thermal stimulation will be 
applied over the dorsal aspect of the right foot.  QST will be performed at the Enrollment 
Visit to obtain a baseline value and on Days 15, 30, 45, 61, 75, 91, 105 and 121.   
2. Secondary Efficacy Assessment 
Nerve Conduction Velocity (NCV): For large myelinated nerve fiber assessments.  Using 
the NC-stat® DPNCheck®, the subject will assume a comfortable position so that their right 
leg is visible (that the subject’s outer ankle bone and Achilles tendon are visible). The 
patient preparation pad is then used to thoroughly clean the subject’s outer lower right leg 
and ankle bone area to remove any residue.  The subject’s right outer ankle bone is then 
identified to align the anode and cathode just behind with the cathode just adjacent to the 
middle of the ankle bone.  The device is aligned on the calf pressing firmly down on the 
foam to ensure contact.  The sural nerve conduction velocity and amplitude will be recorded 
at the Enrollment Visit and end of study visit (Day 121). An increase in velocity and a 
decrease in amplitude would be considered clinically meaningful. 
Skin Perfusion Pressures: Vasamed Sensilase PAD-IQ measures pressure (in mm Hg) of 
microcirculation using a laser Doppler sensor. The patient lies down in a supine position 
and remains silent and still.  The Laser Sensor Assembly (LSA) is inserted into the LSA 
Placement Guide and the optical sensor window is oriented toward the skin.  For those 
subjects who will have biopsies performed, SPP will be obtained prior to the skin biopsies.  
A cuff is positioned so that the LSA is centered on the bladder both horizontally and 
vertically. The pressure of the cuff is then automatically increased to a pressure necessary 
to occlude blood flow and then released at a controlled rate and a measurement of the 

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pressure in the angiosome is made. SPP (mmHg) at reactive hyperemia is recorded.  A 
second measure of SPP will be obtained on the plantar aspect of the right foot directly below 
the location where the SPP was performed on the dorsal aspect of the right foot.  SPP will 
be conducted at the Enrollment Visit, Day 61, and end of study visit (Day 121).  An increase 
in SPP would be considered clinically meaningful. 
Pain Intensity (PI): a validated 11-point Numeric Pain Rating Scale (NPRS) with scores 
(0-10) collected as patient-reported outcomes on a paper diary, at Screening for eligibility, 
at the Enrollment Visit for a baseline value, and Days 61, 75 and 91 to assess response (1-
point decrease from baseline in average pain score over the last 24 hours). On the diary, PI 
will be assessed after each morning (8am ± 2 hours) treatment.  Subjects will report their 
average pain score over the last 24 hours.  Diaries will be distributed and collected from the 
subjects every 2 weeks to ensure compliance.   
Brief Pain Inventory (BPI): is a 32-question long form questionnaire that assesses the 
severity of pain and its impact on specific daily functions.  Cronbach’s alpha reliability 
ranges from 0.77-0.91. The BPI long form will be administered at the Enrollment Visit, Day 
30, 61, 91, and end of study visit (Day 121).  The change from baseline will be captured and 
assessed. 
Brief Fatigue Inventory (BFI): is a 4-question assessment that assesses the level of fatigue 
and the impact of the fatigue on daily function over the last 24 hours.  A global fatigue score 
is collected by averaging all items on the BFI. Cronbach’s alpha reliability ranges from 
0.82-0.97. BFI is patient reported and collected at the Enrollment Visit, Days 30, 61, 91, 
and end of study visit (Day 121).  The change from baseline will be captured and assessed. 
Patient Global Impression of Change (PGIC): a 7-point validated categorical scale of 
overall change in status since initiation of treatment with the study device. PGIC allows 
subjects to integrate into one overall evaluation of the different aspects of their response to 
treatment, including pain reduction, improvement in functioning and side effects. PGIC will 
be collected every 7 days in the paper diary, immediately following the morning treatment.  
PGIC serves to anchor within-subject changes in pain over the course of treatment.   
In a single question, subjects will be asked to describe their overall status compared to the 
start of the study (“Since the start of the study, my overall status is:”), and to score it as 
either very much worse, much worse, minimally worse, no change, minimally improved, 
much improved or very much improved (Appendix C). “Much Improved” and “Very Much 
Improved” are considered clinically meaningful results.1 PGIC will be collected in the paper 
diary every 7 days immediately following the morning treatment during the 120-day 
treatment period.  PGIC serves to anchor within-subject changes in pain over the course of 
treatment. 
                                                          
 

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Hospital Anxiety and Depression Scale (HADS): is a patient reported assessment that 
detects stats of depression and anxiety.  The subscales within the assessment assess the 
severity of the emotional disorder connected to having diabetic peripheral neuropathy.  
Subjects will complete the assessment at the Enrollment Visit, Days 30, 61, 91, and end of 
study visit (Day 121). 
NeuroQoL: is a validated measure that measures the effects of diabetic peripheral 
neuropathy and its complications on an individual’s quality of life. The questionnaire will 
be completed by the subject at the Enrollment Visit and end of study visit (Day 121). 
3. Exploratory Efficacy Assessment 
Biopsy:  To assess c-fiber nerve density when treatment with Provant is administered.  
Biopsies will be taken from subjects that consent to them being taken.  At least 2 subjects 
per pain phase category will be consented.  One biopsy will be obtained at the distal leg, 
10cm above the lateral malleolus on the right leg.  A second biopsy will be obtained at the 
distal thigh, 10cm above the superior margin of the patella on the right leg.  Both biopsies 
will be taken at the Enrollment Visit.  The biopsies will be shipped overnight to the central 
lab.  At the Day 121 Visit, a second set of biopsies will be obtained to the right of the 
baseline biopsies on the same subjects that consented at enrollment and shipped overnight 
to the central lab.  At the end of the study, the biopsies will be compared to assess nerve 
fiber density. 
4. Additional Study Assessments 
Measurement of Ankle-Brachial Index (ABI): Subject is in a supine position, with the 
arms and legs at the same level as the heart for a minimum of 10 minutes before 
measurement to obtain the ABI measurement.  ABI will be measured at the Screening Visit 
and the end of study visit (Day 121) on both legs.  At Day 121, for those subjects who will 
have biopsies performed, ABI will be completed prior. The change from baseline will be 
captured and assessed. 
Measurement of Foot Thickness: The depth of the foot (H) will be measured from the 
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on the treatment pad (see diagram below).  The depth should not be more than 8cm for 
inclusion in the trial. 
 
 
Hemoglobin A1c (HbA1c) Test: provides the average level of glucose in the blood over 
the past 2 to 3 months.  For this test, the A1C Now® System will be used, subjects will have 
a finger stick to collect 5µL of blood to obtain the A1c value at the Screening Visit to obtain 
eligibility (and baseline).  At the end of the study visit (Day 121) the A1c will be collected 
and compared to the baseline value.  Each subject will have a A1C Now® System assigned 
to them.  The change from baseline will be captured and assessed.    
Blood Glucose: measures the amount of sugar in the blood at the time of collection.  A 
TRUE METRIX® PRO Professional Monitoring Blood Glucose System will be assigned to 
each subject for the course of the study.  Subjects will have a finger stick to collect 5µL of 
blood to measure their glucose value at the Enrollment Visit and on Days 30, 61, 91, and 
121.  The American Diabetes Association’s goals for blood glucose control in patients with 
diabetes is 70 to 130 mg/dL before meals and less than 180mg/dL after meals. 
Subject adherence: compliance with twice daily treatment with the study device will be 
assessed verbally during the Day 3 telephone call, at the interim visits and upon completion 
of the study.  At each of the interim visits, subjects will be required to bring in their devices 
to ensure compliance by recording the usage meter reading on the side of the study device 
control panel. 
Treatment Satisfaction: will be obtained at Days 15, 30, 45, 61, 75, 91, 105, and end of 
study visit to assess the patients level of satisfaction with the treatment.  Once subjects are 

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randomized, they will also be asked which device (active of sham) they believe they were 
randomized to at Day 121 (blinding assessment). 
5. Safety Assessments 
Safety will be assessed through review of AE reports and concomitant treatments and 
medications. All concomitant drug or non-drug treatments used during the study will be 
recorded. Safety outcomes will be assessed at the interim visits and the Day 121 visit. 
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 in the trial.  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, 
race/ethnicity) 
4. Collect Medical and Surgical History  
5. Collect depth of the foot measurement from right foot 
6. Conduct directed physical exam  
7. Obtain Ankle-Brachial Index 
8. Assess venous insufficiency 
9. Measure HbA1c 
10. Review and record all concomitant medications 
11. Perform a urine pregnancy test for females of child bearing potential  
12. Obtain patient completed Michigan Neuropathy Screening Instrument 
13. Administer a urine drug screen 
14. Assess Pain Phase (at least 10 subjects in each pain phase) 
15. If the subject meets the eligibility criteria, continue to Enrollment Visit.  
If the subject does not require any washout for prohibited medications or procedures, the 
Screening and the Enrollment Visits can be conducted concurrently.   

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All subjects will provide a urine sample for a urine drug screen. The test is intended to 
identify methamphetamine, cocaine and heroin for purposes of excluding subjects who are 
abusing illicit drugs, and hydrocodone, oxycodone and methadone for purposes of 
confirming the use of prescribed opioids. The urine drug screen test kit, Reveal 7 Panel Cup, 
from American Screening Corporation, will be provided by the sponsor to the investigative 
site for use at point-of-collection. 
B. 
Visit 2 – Enrollment Visit (Day 0) 
  The following procedures will be performed: 
1. Review Inclusion/Exclusion criteria (if visits not combined) 
2. Review and record any changes in medical history and study eligibility criteria since 
screening (if visits not combined) 
3. Collect Baseline Health Economics  
4. Review and record adverse events (if visits not combined) 
5. Review and record any changes in concomitant medications (if visits not combined) 
6. Conduct VPT 
7. Conduct Quantitative Sensory Testing (QST) of Heat and Cold 
8. Conduct NCV  
9. Collect subject’s average pain score 
10. Measure blood glucose 
11. Collect BPI, BFI, HADS, NeuroQoL  
12. Conduct SPP  
13. Collect Biopsy of from consented subjects (at least 2 subjects per pain phase 
category) 
14. If the subject continues to meet eligibility criteria, dispense active study devices 
15. Introduce and train the subject on the use of the PROVANT® Therapy System, 
including instructions for proper positioning and operation of the devices. 
16. Distribute the diary and instruct subject how to complete. 
During this visit, eligible subjects will receive two active PEMF devices and 120 Disposable 
Applicator Covers per device (4 packs of 30) and the subject will be instructed to administer 
treatment on both feet twice daily at 8am and 8pm (+ 2 hours) for 60 days.  
 

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C. 
Day 3 Phone Call (Day 3 +2 Days) 
A telephone call follow-up will be performed and the following will be assessed: 
1. Review and record adverse events 
2. Review and record all concomitant medications 
3. Assess adherence to PEMF treatment regimen and diary completion 
 
D. 
Day 15 Interim Visit (Day 15 + 3 Days) 
Subjects will return to the clinic on Day 15 with their devices.  At this visit, the following 
procedures will be performed: 
1. Conduct VPT 
2. Conduct QST 
3. Collect diary and dispense a new diary for the next two weeks 
4. Review and record adverse events 
5. Review and record all concomitant medications 
6. Assess adherence to PEMF treatment regimen by monitoring the usage meter 
7. Assess treatment satisfaction 
 
E. 
Day 30 Interim Visit (Day 30 + 3 Days) 
Subjects will return to the clinic on Day 30 with their devices.  At this visit, the following 
procedures will be performed: 
1. Conduct VPT 
2. Conduct QST 
3. Measure blood glucose 
4. Collect BPI, BFI, HADS 
5. Collect diary and dispense a new diary for the next two weeks 
6. Review and record adverse events 
7. Review and record all concomitant medications 
8. Assess adherence to PEMF treatment regimen by monitoring the usage meter 
9. Assess treatment satisfaction 
 

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F. 
Day 45 Interim Visit (Day 45 + 3 Days) 
Subjects will return to the clinic on Day 45 with their devices.  At this visit, the following 
procedures will be performed: 
1. Conduct VPT 
2. Conduct QST 
3. Collect diary and dispense a new diary for the next two weeks 
4. Review and record adverse events 
5. Review and record all concomitant medications 
6. Assess adherence to PEMF treatment regimen by monitoring the usage meter 
7. Assess treatment satisfaction 
 
G. 
Day 61 Visit (Day 61 +3 Days) 
Subjects will return to the clinic on Day 61 with their devices.  At this visit, the following 
procedures will be performed: 
1. Conduct VPT 
2. Conduct QST 
3. Measure blood glucose 
4. Conduct SPP 
5. Collect BPI, BFI, HADS 
6. Collect subject’s average pain score 
7. Collect diary and dispense a new diary for the next two weeks 
8. Review and record adverse events 
9. Review and record all concomitant medications 
10. Assess adherence to PEMF treatment regimen by monitoring the usage meter 
11. Assess treatment satisfaction 
12. Assess response 
o If a subject is determined to be a responder (based upon a 1-point decrease 
in average pain score over the last 24 hours using the NPRS) return the active 
devices and randomize the subject per the schedule. 
o If the subject is determined to be a non-responder, instruct the subject to 
continue treating with the active devices and dispense additional DACs. 
 

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H. 
Day 75 Interim Visit (Day 75 + 3 Days) 
Subjects will return to the clinic on Day 75 with their devices.  At this visit, the following 
procedures will be performed: 
1. Conduct VPT 
2. Conduct QST 
3. Collect subject’s average pain score (if non-responder at Day 61) 
4. Collect diary and dispense a new diary for the next two weeks 
5. Review and record adverse events 
6. Review and record all concomitant medications 
7. Assess adherence to PEMF treatment regimen by monitoring the usage meter 
8. Assess treatment satisfaction 
9. Assess response for non-responders at Day 61 
o If a subject is determined to be a responder (based upon a 1-point decrease 
in average pain score over the last 24 hours using the NPRS) return the active 
devices and randomize the subject per the schedule. 
o If the subject is determined to be a non-responder, instruct the subject to 
continue treating with the active devices and dispense additional DACs. 
 
I. 
Day 91 Visit (Day 91 +3 Days) 
Subjects will return to the clinic on Day 91 with their devices.  At this visit, the following 
procedures will be performed: 
1. Conduct VPT 
2. Conduct QST 
3. Measure blood glucose 
4. Collect BPI, BFI, HADS 
5. Collect subject’s average pain score (if non-responder at Day 61 or 75) 
6. Collect diary 
7. Review and record adverse events 
8. Review and record all concomitant medications 
9. Assess adherence to PEMF treatment regimen by monitoring the usage meter 
10. Assess treatment satisfaction 
11. Assess response for non-responders at Day 75 

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o If a subject is determined to be a responder (based upon a 1-point decrease 
in average pain score over the last 24 hours using the NPRS) return the active 
devices and randomize the subject per the schedule. 
o If the subject is determined to be a non-responder, complete the Day 121 end 
of study visit procedures and return the devices and unused DACs. 
12. Dispense a new diary for the next two weeks to Responders only and additional 
DAC packs as needed. 
 
J. 
Day 105 Interim Visit (Day 105 + 3 Days) 
Subjects will return to the clinic on Day 105 with their devices.  At this visit, the following 
procedures will be performed: 
1. Conduct VPT 
2. Conduct QST 
3. Collect diary and dispense a new diary for the next two weeks 
4. Review and record adverse events 
5. Review and record all concomitant medications 
6. Assess adherence to PEMF treatment regimen by monitoring the usage meter 
7. Assess treatment satisfaction 
8. Dispense additional DAC packs as needed. 
 
K. 
Day 121 Visit (Day 121 + 3 Days)  
Subjects will return to the clinic on Day 121 for the end of study visit. At this visit, the 
following procedures will be performed: 
1. Collect subjects weight 
2. Obtain Ankle-Brachial Index 
3. Assess venous insufficiency 
4. Conduct VPT 
5. Conduct QST 
6. Conduct NCV 
7. Measure blood glucose 
8. Measure HbA1c 
9.  Collect BPI, BFI, HADS, NeuroQoL  

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10. Conduct SPP 
11. Collect diary 
12. Conduct Blinding Assessment 
13. Assess adherence to PEMF treatment regimen by monitoring the usage meter 
14. Assess treatment satisfaction 
15. Obtain skin biopsy from subjects that had a biopsy at baseline 
16. Review and record adverse events 
17. Review and record all concomitant medications 
18. Return of study device and unused DACs  
 
L. 
Treatment adherence/study compliance 
Subject adherence (compliance with twice daily treatment with the study device) will be 
assessed during the interim visits by viewing the usage meter on each device, and upon 
completion of the treatment period at the Day 121 visit by the research staff reading and 
recording the number displayed on the study device usage meter.  The usage meter will read 
0.0 at Enrollment and upon randomization and will increase by 0.5 for each complete 30-
minute treatment. A subject with complete adherence will be expected to have a usage meter 
reading based upon their response date.  
Subjects will be instructed to return all unused DACs at the end of treatment visit. Each 
treatment session requires one new DAC, thus in the course of 120 days of treatment, the 
subject will utilize up to 240 DACs. If a subject is determined to be a non-responder at 
Day 91, they will utilize 180 DACs per PEMF device (360 total). 
M. 
Protocol Adherence 
Strict adherence to all specifications laid down in this protocol is required for all aspects 
of the study conduct. 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.   
N. 
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. Additions to the 
subject’s therapeutic regimen (agent, dose, frequency of administration) for treatment of 
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allowed through Day 121 of the study. Subjects will be allowed to continue administration 
of prn medications on an ad lib basis. Subjects may choose to reduce or discontinue opioid 
or other drug therapies during the treatment period of the study.   
It is important to record the reason why each analgesic is being taken by the subject, 
specifically analgesics taken for treatment of pain associated with diabetic neuropathy.  
Analgesics taken for other reasons, e.g., headache, will be collected through recording of 
concomitant medications in the subject’s chart.   
1. Allowed Medications 
Subjects will be allowed to continue their regimen of analgesic medications from the time 
of the Screening Visit through and including the Day 121 visit. In this context, “analgesic 
medications” refers to medications prescribed and administered for the treatment of pain, 
and includes but is not limited to anticonvulsants, opioids, nonsteroidal anti-inflammatory 
agents, anti-depressants and muscle relaxants. As such, this includes medications taken on 
an “as needed” (prn) basis as well as those medications taken on a regular schedule. Subjects 
may continue to take prn medications on an ad lib basis in response to their pain experience. 
Subjects who experience increased pain during the study will be instructed to increase the 
self-administration of their prescribed prn analgesic(s). Subjects may choose to reduce or 
discontinue prn opioid or other analgesic drug therapies during the treatment period of the 
study, and will be specifically instructed to do so by the investigator if their pain remits.  
Medications prescribed for other indications are allowed and will be recorded as 
concomitant medications. Low dose aspirin (acetylsalicylic acid) 81 mg is allowed if taken 
for cardiac or vascular prophylaxis. 
2. Prohibited Medications/Treatments 
The following medications and therapeutics are prohibited throughout the study: 
 Systemic steroids or topical steroids on the lower extremities 
 Transcutaneous electrical neurostimulators (TENS units) 
 Implanted neurostimulators  
 Local injections  
 Intrathecal infusion 
 Acupuncture  
 Surgery 

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V. 
WITHDRAWAL PROCEDURES 
If a subject is withdrawn from study participation, the subject’s enrollment in the study will 
terminate, study device application will be discontinued and no further data will be collected 
on the subject.  Efforts will be made to perform all assessments scheduled for the Day 121 
Visit prior to subject withdrawal. 
 
A subject may be withdrawn from further study participation under the following 
circumstances: 
 At the subject’s request. 
 Noncompliance with the protocol by the subject. 
 Non-Responder at Day 91 
 Adverse Event (decision to be removed from study made by either the investigator or 
subject). The investigator must notify the sponsor immediately if a subject is withdrawn 
because of an AE. 
 Decision by the investigator or sponsor that termination is in the subject’s best medical 
interest or administrative decision for a reason other than that of an AE. 
 Request for withdrawal by the subject for reasons other than an intolerable AE. 
 Lost to follow-up, as determined by failure to respond to at least 2 telephone calls 
followed by certified letter sent to the subject’s last known address. All attempts to 
contact the subject must be documented in the subject’s source documents. 
VI. 
STATISTICAL CONSIDERATIONS  
The statistical analysis of the study is described in detail in a separate version-controlled prospective 
Statistical Analysis Plan (SAP).  However, the statistical methodology described in this section of 
the protocol will be the basis for the detailed SAP.   
This bi-phasic design includes 2 sequential periods: the Induction Phase and Randomized Withdraw 
Phase.  All safety analyses will be performed on the Safety Analysis Set, defined as all subjects who 
were enrolled into the study and issued study devices during the Induction Phase and followed 
through the Randomization Withdraw Phase or until they withdraw.   Once a subject is determined 
to be eligible, the subject will be issued active treatment devices and the subject will be formally 
enrolled into the study and become part of the Safety Analysis Set.  Where not otherwise specified, 
the last pre-treatment observation will be used as baseline for calculating post-treatment changes 
from baseline.  
A. 
Induction Phase / Baseline Evaluations 
Prior to study treatment, subjects will complete the baseline health economic questions, including 
the Brief Pain Inventory (BPI), Brief Fatigue Inventory (BFI), Hospital Anxiety and Depression 
Scale (HADS), and the NeuroQoL.  Vibration Perception Threshold (VPT), Quantitative Sensory 
Test (QST) and Nerve Conduction Velocity (NCV) will be completed.  Skin Perfusion Pressure 

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(SPP) will be performed to obtain a baseline value of the plantar and dorsal aspect of the right foot.  
Once the subject is determined to be eligible, the subject will be issued active treatment devices and 
the subject will be formally enrolled into the study and become part of the Safety Analysis Set. 
Subjects in the Safety Analysis Set will be instructed in the use of the devices for 60 days in the 
home environment.  At Days 15 and 45, subjects will return to the clinic to have the VPT and QST 
conducted.  Subjects will return to the clinic at days 30 and 61 for evaluation and complete 
questionnaires.     
B. 
Randomized Withdraw Phase 
Randomization of subjects can occur at different times, depending on when the subject is 
determined to be a responder.  Once a subject is determined to be a responder (based upon a 1-point 
decrease in average pain score over the last 24 hours using the NPRS), the subject will return the 
active devices and be randomized 1:1 to receive active treatment or inactive sham devices and be 
instructed to treat through study day 120.  If a subject is determined to not be a responder at Day 
91, i.e., their final chance to be randomized, the subject will be terminated from the study at the end 
of the Day 91 visit. 
C. 
Summarization of Results 
The tabulations will be based on the paired results for the change from the baseline to study day 
120 for patients who are randomized, and separately for the last observation.  Supportive subject 
data listings will be sorted and presented by subject number, visit date and relative study day.  
Listings will also include the number of days relative to the initiation of treatment.  Two sets of 
analyses will be generated; summary tabulations for all randomized subjects who complete the 
baseline and study day 120 evaluations (Completers Analysis Set), and all randomized subjects 
using the baseline and last recorded set of evaluations (End of Study Evaluation Set).  This latter set 
should include all subjects who were randomized and complete at least one set of evaluations after 
randomization.   
Specific algorithms will be described in the Statistical Analysis Plan for imputing missing or 
partially missing dates, if deemed appropriate, under specific data topics.  Imputed or derived data 
will be flagged in the individual subject data listings.  Imputed data will not be incorporated into 
any raw or primary datasets.  The imputed data will be retained in the derived / analysis datasets. 
The total duration for a subject on-study will be calculated as the difference between the date of 
initial study treatment in the Induction Phase and the last day of observation plus 1 day.  All 
calculations for defining the duration on-study will follow the algorithm DURATION = [STUDY 
COMPLETION OR WITHDRAW DATE – INITIAL TREATMENT DATE + 1].   
Summary statistics will consist of the count and percentage in each level for categorical variables, 
and the sample size (n) mean, median, standard deviation (SD), minimum, and maximum values 
for continuous variables.  All mean and median values will be formatted to one more decimal place 

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than the measured value.  Standard deviation values will be formatted to two more decimal places 
than the measured value.  Minimum and maximum values will be presented with the same number 
of decimal places as the measured value.  The number and percentage of responses will be presented 
in the form XX (XX.X%).  Pairwise differences between the treatment groups will be calculated 
and 95% confidence intervals constructed.   
While no formal hypothesis testing is planned, probability values may be generated to determine 
the magnitude of the difference between subject groups for an endpoint.  All p-values that round to 
0.0000 will be presented as ‘<0.0001’ and p-values that round to 1.0000 will be presented as 
‘>0.9999’.  P-values <0.05 will be discussed as being statistically significant.   
All summary tables will include the analysis population sample size (i.e., number of subjects).  
Study Day 1 is defined as the day the subject receives their initial exposure to the active study 
device.  All study days are determined relative to the day of initial treatment with the study device.  
Baseline values will be defined as those values recorded closest to, but prior to, the first active study 
treatment during the initial phase of the study.  Date variables will be formatted as DDMMMYYYY 
for presentation.  Where appropriate, only the measurements from the right foot will be used in the 
calculations. 
D. 
Adverse Events  
All summaries of adverse events will be based on treatment-emergent adverse events.  Adverse 
events will be provided in a listing.  The number and percentage of subjects experiencing adverse 
events will be summarized. Summaries by maximum severity and relationship to the study device 
(active or sham) will also be provided. Serious adverse events and adverse events leading to 
discontinuation from the study will be presented.  Treatment-related adverse events will be defined 
as adverse events with investigator assessment of related or possibly related.  In summaries of 
adverse events by severity and relationship to study device, patients 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 patients with at 
least one adverse event will be tabulated for each treatment group.  The number of adverse events 
for each treatment group will also be tabulated. 
E. 
Sample Size  
This is a proof of concept study with no formal hypothesis testing planned and therefore there is no 
power associated with this study.  The sample size of 40 patients is a sample of convenience for 
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 

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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 should 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, all clinical investigational data will be reviewed by the sponsor on a regular basis.  
Reports of all 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.  
The clinical investigation 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.  
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.   

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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 
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, 

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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 Therapy System  
Anticipated adverse events associated with PROVANT® Therapy System 2  and the procedures and 
medicines used in the study 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)  
 Increased bleeding at surgical site 
 Chilliness 
 Headache 
 Malaise  
 Nausea 
 Abdominal or chest wall discomfort 
 Muscle cramps 
 Excessive menstruation 
 Failure to reduce pain or an increase in pain 
                                                          
2 Reported at least once since market launch in 2004. 

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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.  The protocol will contain all of the anticipated 
Adverse Events that could be associated with the study. 
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 
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. 

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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) will contact 
and visit the investigator regularly and will be allowed, upon request, to inspect the various records 
of the trial (source documents and other pertinent data) provided that subject confidentiality is 
maintained in accord with local requirements. 
It will be the monitor’s responsibility to inspect the patient charts at regular intervals throughout 
the study to verify the adherence to the protocol and the completeness, consistency and accuracy of 
the data.  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 

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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 
1. Centers for Disease Control and Prevention.  National diabetes statistics report:  estimates 
of diabetes and its burden in the United States, 2014.  Atlanta GA: US Department of Health 
and Human Services, Centers for Disease Control and Prevention, 2014. 
2. Wild S, Roglic G, Green A, et al. Global prevalence of diabetes: estimates for the year 2000 
and projections for 2030. Diabetes Care 2004;27(5):1047-1053. 
3. Todorovic SM. Painful Diabetic Neuropathy: Prevention or Suppression?  Int Rev 
Neurobiol. 2016;127:211-25.2016 
4. Russel J. et. al.  Diabetic Neuropathies.  Continuum (Minneap Minn) 2014;20(5):1226–
1240. 
5. Diabetic Neuropathy: A Position Statement by the American Diabetes Association Diabetes 
Care 2017 Jan; 40(1): 136-154. 
6. Boulton AJ, Management of Peripheral Diabetic Neuropathy Clinical Diabetes 2005 Jan; 
23(1): 9-15. 
7. Boulton AJ, Kirsner RS, Vileikyte L. Clinical practice. Neuropathic diabetic foot ulcers. N 
Engl J Med. 2004 Jul 1. 351(1):48-55.  
8. Rice JB, Desai U, Cummings AK, Birnbaum HG, Skornicki M, Parsons NB. Burden of 
diabetic foot ulcers for Medicare and private insurers. Diabetes Care. 2014. 37 (3):651-8. 
9. Singleton JR.  Smith GA.  The Diabetic Neuropathies.  Semin Neurol. 2012;32(3):196-203. 
10. Chou R. et. al. Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic 
Noncancer Pain.  J Pain. 2009 Feb;10(2):113-30. 
11. Barclay V, Collier RJ, Jones A. Treatment of various hand injuries by pulsed 
electromagnetic energy (Diapulse). vol. 69, no. 6, 1983., pp. 186–188. 
12. Brook J, Dauphinee DM, Korpinen J, Rawe IM. Pulsed Radio Frequency Electromagnetic 
Field Therapy: A Potential Novel Treatment of Plantar Fasciitis. vol. 51, no. 3, 2012., pp. 
312–316 
13. Comorosan S, Pana I, Pop L, et al. The influence of pulsed high peak power electromagnetic 
energy (Diapulse) treatment on posttraumatic algoneurodystrophies. 1991;  28:77–81. 
14. FDA MAUDE and MDR databases searched on June 15, 2014 reveals 5 medical device 
reports related to PEMF in any indication. 
15. Foley-Nolan D, et al. Pulsed high frequency (27MHz) electromagnetic therapy for persistent 
neck pain. A double blind, placebo-controlled study of 20 patients. vol. 13, no. 4, 1990., pp. 
445-451. 

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16. 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. vol. 24, 1992., pp. 51-59. 
17. George FR, Lukas RJ, Moffett J, Ritz MC. In vitro mechanisms of cell proliferation 
induction: a novel bioactive treatment for accelerating wound healing. vol. 14, no. 3, 2002., 
pp. 107-115. 
18. Guo L, Kubat NJ, Isenberg RA. Pulsed radio frequency energy (PRFE) use in human 
medical applications. vol. 30, no. 1, 2011., pp. 21-45. 
19. Guo L, Kubat NJ, Nelson TR, Isenberg RA. Meta-analysis of clinical efficacy of pulsed 
radio frequency energy treatment. vol. 255, no. 3, 2012., pp. 457-467. 
20. Moffett J, Kubat NJ, Isenberg RA. Pulsed radio frequency energy as an effective pain 
treatment. vol. 11, no. 3, 2011., pp. 71-73. 
21. 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. vol. 13, no. 4, 2012., pp. S42. 
22. Moffett J, Fray L, Kubat N. Activation of Endogenous Opioid Gene Expression in Human 
Keratinocytes and Fibroblasts by Pulsed Radio Frequency Energy Fields. vol. 5, 2012., pp. 
347-357. 
23. Pennington G.M., et al., Pulsed, non-thermal, high-frequency electromagnetic energy 
(DIAPULSE) in the treatment of grade I and grade II ankle sprains. vol. 158, no. 2, 1993., 
pp. 101-104. 
24. 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.  vol. 125, no. 6,  2010., pp. 1620-29. 
25. 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 seven symptomatic but non-surgical cases. vol. 12, no. 1, 2002., pp.10-
20.  
26. 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. vol. 72, 
no. 11, 1986., pp. 563-566. 
27. Wilson DH. Treatment of soft-tissue injuries by pulsed electrical energy. Br Med J 1972; 2: 
269–270. 
28. Dworkin R, O’Connor A, Audette J, Baron R. Recommendations for the Pharmacological 
Management of Neuropathic Pain: An Overview and Literature Update. Mayo Clin Proc, 
vol. 85, 2010. 

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29. Vileikyte L, Gonzalez JS. Recognition and management of psychosocial issues in diabetic 
neuropathy. Handb Clin Neurol. 2014; 126:195-209.  
 
30. Vileikyte L, Peyrot M, Gonzalez JS, Rubin RR, Garrow AP, Stickings D, Waterman C, 
Ulbrecht JS, Cavanagh PR, Boulton AJ.  Predictors of depressive symptoms in persons 
with diabetic peripheral neuropathy: a longitudinal study. Diabetologia. 2009 Jul; 52(7): 
1265-73. 
 
31. Vileikyte L, Leventhal H, Gonzalez JS, Peyrot M, Rubin RR, Ulbrecht JS, Garrow A, 
Waterman C, Cavanagh PR, Boulton AJ. Diabetic peripheral neuropathy and depressive 
symptoms: the association revisited. Diabetes Care. 2005 Oct;28(10):2378-83. 
 
32. Vileikyte L, Peyrot M, Bundy C, Rubin RR, Leventhal H, Mora P, Shaw JE, Baker P, 
Boulton AJ. The development and validation of a neuropathy-and foot ulcer-specific 
quality of life instrument. Diabetes Care. 2003 Sep; 26(9):2549-55. 
 

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APPENDIX A - TIME AND EVENTS SCHEDULE 
Period 
Screening 
Visit 
Enrollment 
(Baseline) 
Visit 
Day 3 
Phone 
Call 
Day 15 
Visit 
Day 30 
Visit 
Day 45 
Visit 
Day 61 
Visit 
Day 75 
Visit 
Day 91 
Visit 
Day 105 
Visit 
Day 121 
Visit 
Study Day 
-14 - 0 
0 
3 (+2) 
15 (+3) 
30 (+3) 
45 (+3) 
61 (+3) 
75 (+3) 
91 (+3) 
105 (+3) 
121 (+3) 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Demographic Information 
X 
 
 
 
 
 
 
 
 
 
 
Medical/Surgical History/Physical Exam 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
X1 
 
 
 
 
 
 
 
 
 
Baseline Health Economics 
 
X 
 
 
 
 
 
 
 
 
 
Pain Score Assessment (NPRS) 
X 
X 
 
 
 
 
X 
X14 
X4 
 
 
Michigan Neuropathy Screening Instrument 
X 
 
 
 
 
 
 
 
 
 
 
Pain Phase Assessment 
X 
 
 
 
 
 
 
 
 
 
 
Urine Drug Screen  
X 
 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test 
X2 
 
 
 
 
 
 
 
 
 
 
Height and Weight 
X 
 
 
 
 
 
 
 
 
 
X7 
Measurement of Foot Thickness 
X 
 
 
 
 
 
 
 
 
 
 
Obtain Ankle-Brachial Index (ABI) & Assess Venous Insufficiency 
X 
 
 
 
 
 
 
 
 
 
X3 
Vibration Perception Threshold (VPT) 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Quantitative Sensory Test (QST) 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Sural Nerve Conduction Velocity (NCV) 
 
X 
 
 
 
 
 
 
 
 
X 
Measure Blood Glucose 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Measure HbA1c 
X 
 
 
 
 
 
 
 
 
 
X 
Brief Pain Inventory (BPI) 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Skin Perfusion Pressure (SPP) 
 
X 
 
 
 
 
X 
 
 
 
X 
Brief Fatigue Inventory (BFI) 
 
X 
 
 
X 
 
X 
 
X 
 
X 
Hospital Anxiety and Depression Scale (HADS) 
 
X 
 
 
X 
 
X 
 
X 
 
X 
NeuroQoL  
 
X 
 
 
 
 
 
 
 
 
X 
Dispense Active Study Device 
 
X 
 
 
 
 
 
 
 
 
 
Study Device Training 
 
X 
 
 
 
 
 
 
 
 
 
Randomize and Dispense Study Device 
 
 
 
 
 
 
X5 
X9 
X10 
 
 
Distribute Diary (NPRS, PGIC)6 
 
X 
 
X 
X 
X 
X 
X 
X11 
X 
 
Collect Diary 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Study Device Blinding Assessment 
 
 
 
 
 
 
 
 
 
 
X 
Response Assessment 
 
 
 
 
 
 
X5 
X14 
X4 
 
 
Assess Adverse Events  
X8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess Subject Adherence to Treatment 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Treatment Satisfaction 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Return Study Device and Unused DACs 
 
 
 
 
 
 
 
 
X13 
 
X 
3mm Skin Punch Biopsy at distal leg and distal thigh 
 
X12 
 
 
 
 
 
 
 
 
X12 
1. 
The Screening Visit and the Enrollment Visit may occur on the same day in which I/E criteria will not need to be reviewed. 

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2. 
Urine pregnancy test will be performed on women of child-bearing potential.  
3. 
ABI and Venous Insufficiency will be obtained at Day 121 for those subjects who were responders completing treatment through Day 120. 
4. 
Only subjects determined to be non-responders at Day 75 will be assessed.  Subjects determined to be non-responders at Day 91 will be terminated from the study. 
5. 
Non-responders at Day 61 will continue treating with the Active device. Response will again be assessed at Day 75. 
6. 
Numeric pain scores along with weekly PGIC will be recorded by the subject on the diary each day immediately after the morning treatment. 
7. 
Collect only weight at end of study visit. 
8. 
Assessment of adverse events will be conducted after the signing of the Informed Consent. 
9. 
Subjects determined to be responders at Day 75 will be randomized to active or sham and continue treating through Day 120. 
10. Subjects determined to be responders at Day 91 will be randomized to active or sham and continue treating through Day 120. 
11. A new diary is dispensed only to subjects who are responders. 
12. A 3mm skin punch biopsy will be obtained from at least 2 subjects in each pain phase category at the Enrollment Visit and at Day 121. 
13. Only subjects determined to be non-responders will return their study devices and unused DACs at Day 91. 
14. Only subjects determined to be non-responders at Day 61 will be assessed.  Non-responders at Day 75 will continue treating with the Active device. Response will 
again be assessed at Day 91. 
 
 

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APPENDIX B - PAIN PHASE ASSESSMENT SCALE 
 
Intermittent pain and 
numbness interval increase 
in pain and numbness 
more frequent and intense 
Constant pain, usually on 
medication, trouble sleeping 
Moments of relief, less 
pain, more numbness 

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APPENDIX C – SUBJECT DIARY FOR DAILY PAIN SCORE AND WEEKLY GLOBAL 
IMPRESSION OF CHANGE 
 
PATIENT: _____________________ 
 
Week Start Date: _____________________ 
 
Treat Both Feet, Simultaneously, Twice Daily for 30 minutes, 8am +/- 2 hours and 8pm +/- 2hours. 
 
Circle the Pain Score which represents your average Pain over the last 24 hours after completing your 
Morning (am) treatment. 
On the scale below, a score of 0 represents No Pain whereas a score of 10 represents the Worst 
Possible Pain.  Every 7 days, mark your overall status compared to the start of the study. 
 
 
 
 
No 
Pain 
 
 
 
 
 
 
 
 
 
Worst 
Possible 
Pain 
Date: _________ 0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Date: _________ 0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Date: _________ 0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Date: _________ 0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Date: _________ 0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Date: _________ 0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Date: _________ 0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Since the start of the study, my overall status is: 
(check one box only) 
 Very Much Worse         
 Much Worse       
 Minimally Worse        
 No Change     
 Minimally Improved      
 Much Improved        
 Very Much Improved  
 
 

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APPENDIX D – INSTRUCTIONS FOR OBTAINING ANKLE-BRACHIAL INDEX 
 
Measurement of Ankle-Brachial Index 
1. Place the patient in the supine position, with the arms and legs at the same level as the heart, for a 
minimum of 10 minutes before measurement. 
 
2. Select an appropriately sized blood pressure cuff for both the ankle and the arms (see the images below); 
the cuff width should be, at a minimum, 20% greater than the diameter of the extremity.  
a. For the brachial systolic pressure, make sure you have appropriately sized upper-extremity cuff.  
b. For the ankle systolic pressures, make sure that cuff completely encircles lower extremity. The 
ankle cuff should go on the leg between the malleolus and the calf. Enough room should be left 
below both cuffs to permit placement of the ultrasound gel, so that the Doppler device can 
adequately detect the brachial, dorsalis pedis (DP), and posterior tibial pulses (PT). 
 
3. Obtain the brachial systolic pressures of both arms (see the images below), and choose the higher of the 
2 values as the brachial systolic pressure (the difference between them should be less than 10 mm Hg). 
The brachial pulse is best appreciated on the medial side of the antecubital fossa. 
 
4. Obtain the anterior tibial and posterior tibial systolic pressures of the extremity in question (see the 
images below), and select the higher of the 2 values as the ankle pressure measurement. The posterior 
tibial pulse is best appreciated just dorsal and inferior to the medial malleolus. The dorsalis pedis pulse 
is best appreciated on the dorsum of the foot between the proximal section of the first and second 
metatarsals, usually above the navicular bone. Palpate artery. Dorsalis pedis is palpated by hand before 
Doppler device is used. Place small amount of ultrasound transmission gel at landmark where the artery 
was located. Locate artery with Doppler device. Posterior tibial artery is located and marked with gel. 
Identify artery with Doppler device. Upon application of Doppler probe, arterial pulsations should be 
audible. If they are not, reposition probe until appropriate sound is obtained. 
 
5. Do not obscure artery with cuff; you will need to be able to palpate artery and/or locate it with Doppler 
device. As with each appropriately identified arterial site, mark site with ultrasound transmission gel 
after palpation.  Locate artery with device. Typically, Doppler probe must be positioned at 45-60 
degrees, not at 90 degrees as shown. 
 
6. Finally, divide the ankle pressure by the brachial artery pressure; the result is the ABI. 
 
Obtained from: http://emedicine.medscape.com/article/1839449-overview#aw2aab6b4 
 
 
 
 
 
 
 
 

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Brachial Systolic Pressure 
  
 
  
 
 
 
Anterior Tibial and Posterior Tibial Systolic Pressures 
 
  
   
 
 
 
 
 
 
 
 
 

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APPENDIX E – GRADING SYSTEM FOR VENOUS INSUFFICIENCY 
 
VENOUS INSUFFICIENCY CLASSIFICATION SYSTEM (CEAP) 
For the initial assessment of a patient with venous insufficiency, the clinical severity is established by 
observation (without any specialized testing).  The classification system increases in severity from C0-C6 
as noted below. 
 
Patients with C3-6 disease demonstrate an increasing severity of chronic venous insufficiency with chronic 
irreversible functional abnormality of the venous system. Patients with foot edema that typically resolves 
overnight is generally classified as a C2 (as long as they do not also meet criterion for C5 or C6).  Patients 
with persistent ankle edema, gaiter lipodermatosclerosis, and history of a healed ulcer or current open ulcer 
will be excluded from the trial as a consequence of their increased risk of developing a chronic non-
healing venous ulcer after biopsy. 
 
Grade 
Description 
C 0 
No evidence of venous disease. 
C 1 
Superficial spider veins (reticular veins) only  
C 2 
Simple varicose veins only 
C 3 
Ankle edema of venous origin (not foot edema) 
C 4 
Skin pigmentation in the gaiter area (lipodermatosclerosis) 
C 5 
A healed venous ulcer 
C 6 
An open venous ulcer