Trialing of PM Modulation Therapy in Patients With Chronic Intractable Low Back Pain With or Without Leg Pain
Phase: NA
Conditions: Chronic Pain
Sponsor: Stimgenics LLC

Trialing of PM modulation therapy in patients with chronic intractable back pain with or without leg pain. 
 
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PROTOCOL 
 
Trialing of PM modulation therapy in patients with chronic intractable 
low back pain with or without leg pain  
 
SGEN-2017PM1 
 
Sponsor: 
StimGenics     
2406 East Empire Street 
Bloomington, IL 61704 
 
 
Principal Investigator: 
[__________________] 
 
Date of Protocol:  24 April 2017 
Version: 1.1 
 
 
The study will be conducted according to the protocol and in compliance with 
Good Clinical Practice and other applicable regulatory requirements. 
 
 
This document contains confidential information of StimGenics.  Do not copy or 
distribute without written permission from the sponsor. 
CONFIDENTIAL 
 

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PROTOCOL SUMMARY 
 
Study Title: Trialing of PM modulation therapy in patients with chronic intractable lower back 
pain with or without leg pain.  
 
Purpose of the study: To determine the feasibility of PM modulation therapy in patients with 
chronic intractable lower back pain with or without leg pain. 
 
Objective: Demonstrate that spinal cord stimulation using multiple simultaneous waveforms 
provides pain relief in patients suffering chronic intractable low back pain with or without leg 
pain. 
 
Trial design: This is a prospective, open label, observational cross-over study in which pain relief 
from a PM modulation therapy, polymodal spinal cord stimulation (PM-SCS), will be compared 
to conventional spinal cord stimulation.  Up to 25 patients will be included in the study. Standard 
evaluation phase to test the subject’s response to commercial SCS system will be conducted for 
4 ± 1 days. After a washout period of up to 1 day, polymodal spinal cord stimulation therapy (PM-
SCS) will be applied after conventional spinal cord stimulation (SCS) therapy for 4 ± 1 days.  
 
Treatment: Enrolled patients will receive polymodal SCS therapy after receiving conventional SCS 
as part of their therapy trial period. Polymodal stimulation will utilize two trial leads (with eight 
electrodes each), which have been implanted in the epidural space following standard clinical 
practices and as part of a standard spinal cord stimulation trial period. Each lead will be 
connected to the output channel of an external neurostimulation unit (ENS) designed to safely 
deliver either conventional or polymodal electrical signals to the leads. During conventional SCS, 
arrays of electrodes in the leads will be set to deliver conventional parameters that produce 
paresthesia coverage of the painful area following standard programming protocols. After the 
conventional SCS therapy trial phase has been completed (4 ± 1 days), there will be a washout 
period of up to one day before the patient crosses over to polymodal SCS therapy, which will be 
administered for 4 ± 1 days. During polymodal SCS, an array of electrodes in one of the leads is 
set to deliver a charge-balanced, pulsed electrical signal with stimulation parameters (frequency, 
pulse width, and amplitude) that differ from the parameters set in another set of electrodes in 
the other lead.  
The patient will be educated and trained on operation of a remote controller that allows the 
patient to operate the ENS and stimulation therapy programs available within. The patient will 

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also be instructed on troubleshooting both the ENS and remote controller (i.e. changing 
batteries, etc.).  
Pain relief will be assessed in terms of the level of pain before SCS therapy and in comparison 
with level of pain when conventional SCS and polymodal SCS were trialed.  
 
Primary endpoint: 
1. Back Pain reduction relative to baseline pain (i.e. prior to SCS) at day 5 post-initiation 
of a particular SCS therapy (conventional or polymodal). 
 
Secondary endpoints: 
1. Percentage change relative to baseline back pain (i.e. prior to SCS) at day 5 post-initiation 
of a particular SCS therapy (conventional or polymodal). 
2. Responder rate to therapy, defined as the number of patients that were successful with 
therapy relative to the total number of patients receiving therapy. Success of therapy is 
defined as a 50% or more reduction in back pain. 
3. Patient subjective evaluation of whether a patient experienced paresthesia with PM-SCS 
or not.  
4. Patient subjective satisfaction with PM-SCS and conventional SCS and therapy of choice.  
5. Incidence of adverse events. 
 
Inclusion Criteria: 
 
1. Capable of giving written informed consent to participate in this clinical study based on 
voluntary agreement after a thorough explanation of the patient’s participation is 
provided to them. 
2. Chronic intractable pain of the lower back equal to or greater than pain in lower limbs, 
and that has been refractory to conservative therapy for ≥ 3 months. 
3. Must be older than 18 years old. 
4. Average back pain intensity of ≥ 5 out of 10 on the numerical pain rating scale (NPRS). 
5. Appropriate candidate for spinal cord stimulation trial. 
6. Subjects must be on a stable dose of pain medication regimen for at least one month. 
7. Female patients who are not pregnant and do not plan to become pregnant during the 
study.  Females of child bearing potential must provide a negative pregnancy test and 
must be using reliable contraception and must continue to use reliable contraception 
until study completion.  Non-childbearing potential is defined as postmenopausal for at 
least 2 years or surgical sterilization or hysterectomy at least 3 months before study start. 
Patients who become pregnant or who have a spouse/significant other that becomes 

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pregnant during the course of this study agree to report pregnancy to the study 
physician/staff. 
8. Must be able to comply with the requirement of study visits and follow-up and phone 
visits. 
9. Have cognitive ability of operate the remote control and follow therapy instructions and 
directions by clinicians. 
Exclusion Criteria: 
 
1. Systemic infection. 
2. Any active implanted device. 
3. Previous experience with SCS therapy either during a trial or fully implanted 
4. Evidence of serious neurological, psychological or psychiatric disorders. 
5. Mechanical spinal instability. 
6. Patients with uncorrected coagulation disorders or who are on anticoagulation therapy 
and cannot interrupt the therapy. 
7. Patient who are pregnant, breast-feeding or women of childbearing potential with 
positive pregnancy tests.   
8. Human immunodeficiency virus (HIV) infection or a clinically significant infection. 
9. Patients who are undergoing or will undergo therapies or diagnostics that involve 
electromagnetic fields such as: diathermy based therapies, electrocautery, magnetic 
resonance imaging (MRI), radiofrequency (RF) or microwave ablation, bone growth 
stimulators, 
electrolysis, 
therapeutic 
ultrasound, 
ultrasound, 
lithotripsy, 
psychotherapeutic procedures, radiation therapy, and transcutaneous electrical nerve 
stimulation.  
10. A clinically significant disorder such as cerebrovascular disease, pulmonary infarction, 
ischemic heart disease, cardiac dysrhythmia, myocardial infarction, or congestive heart 
failure or any other as determined by the investigator. 
11. Uncontrolled diabetes, uncontrolled pulmonary disease, or uncontrolled hypertension. 
12. Patients who have evidence of major psychiatric disease, mental disorder, drug 
dependency, alcohol dependency, or substance abuse disorders. 
13. Patients who have progressive neurological disease such as multiple sclerosis, chronic 
inflammatory demyelinating polyneuropathy, rapidly progressive arachnoiditis, acute 
herniated disc, or any other as determined by investigator. 
14. Medical condition or pain in other body areas that could interfere with study procedures, 
accurate pain reporting, and/or confound evaluation of study end points. 
15. Concurrent participation in another clinical study. 
16. Involvement in an injury claim under current litigation or a pending or approved workers’ 
compensation claim. 

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Schedule of Events: 
 
 
Event\Activity 
Enrollment/
Baseline 
(Day 0) 
Start of SCS Trial 
(0-30 days after 
enrollment/baseline) 
Crossover to 
Polymodal SCS 
(3-5 days after 
start of trial) 
End of Study 
(3-5 days after 
crossover to PM-SCS) 
Informed Consent 
X 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
Pregnancy TestA 
X 
 
 
 
General Health and 
Pain Medications  
X 
 
 
 
Pain NPRS 
X 
 
X 
X 
Informed Consent 
Reaffirmation 
X 
 
 
 
Lead Implantation 
 
X 
 
 
X-ray Fluoroscopy 
 
X 
X 
X 
Programming of 
Conventional SCS and 
start of trial 
 
[X] 
 
 
Programming of PM-
SCS 
 
 
[X] 
 
Stimulation Sensation 
Assessment 
 
 
 
 
X 
Impression of 
Improvement and 
Patient Satisfaction 
 
 
 
 
X 
Adverse Event 
Assessment 
 
X 
X 
X 
A Administered only to subjects of childbearing potential 
[X] Optional reprogramming (conventional or polymodal SCS) visits are allowed at the discretion of the 
investigator and depending on the feedback from standard of care follow up phone visits.  
 
 
 

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TABLE OF CONTENTS 
 
 
 
 
 
 
 
 
 
PAGE 
 
Protocol Summary .............................................................................................................. 3 
Table of Contents ............................................................................................................... 8 
Signature Page ................................................................................................................... 9 
List of Abbreviations ......................................................................................................... 10 
1. 
Background/Scientific Rationale ................................................................................. 11 
2. 
Risks and Benefits ..................................................................................................... 13 
3.  
Objectives ................................................................................................................ 17 
4. 
Eligibility .................................................................................................................. 18 
5. 
Design and Procedures .............................................................................................. 20 
6. 
Data Collection and Analysis ...................................................................................... 25 
7. 
Devices .................................................................................................................... 28 
8. 
Conduct of study ...................................................................................................... 30 
9. 
References ............................................................................................................... 33 
10.  Appendices .............................................................................................................. 36 
 
 
 

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SIGNATURE PAGE 
Investigator Signature 
I have read this protocol and agree to conduct the investigation according to the requirements 
of the study protocol and in accordance with Good Clinical Practice, applicable State and Federal 
regulations and conditions imposed by the reviewing Investigational Review Board. As the 
Principal Investigator of the study, I agree to supervise all sub-investigators at my site as well as 
the use of all of the investigational devices and to ensure appropriate informed consent is 
obtained for all subjects prior to inclusion in the study. 
Signed: 
 
Date: 
 
 
Name: _______________________________ 
Title: _Principal Investigator______________ 
 
 
Confidentiality Statement 
All information concerning the study device supplied by StimGenics in connection with this study, 
and not previously published, is considered confidential and proprietary information. This 
information includes the clinical protocol and its appendices, subject informed consent form, 
product labelling (user manuals for patient and clinician), and case report forms. This confidential 
information shall remain the sole property of StimGenics, and shall not be disclosed to others 
without previous written consent by StimGenics. This confidential information shall not be used 
except for the performance of the study. 
All the information communicated and developed during the conduct of the study shall be 
considered confidential and proprietary. This information will be used by StimGenics in 
connection with the development of polymodal spinal cord stimulation therapy. This information 
may be disclosed as deemed necessary by StimGenics.  
The data and information gathered from the study will not be the subject of publication by the 
individual study site and without prior consent from StimGenics.  

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LIST OF ABBREVIATIONS  
A 
 
 
Amplitude of electric signal (in units of current: Ampere) 
AE 
 
 
Adverse Event 
CE 
 
 
Conformité Européenne 
CFT 
 
 
Clinical Field Technician 
CRF 
 
Case Report Form 
CRO 
 
Contract Research Organization 
EMI 
 
Electromagnetic interference 
ENS 
 
External Neurostimulation Unit 
F 
 
Frequency of pulsed electric signals (in units of Hz) 
GCP 
 
Good Clinical Practice 
Hz 
 
Hertz, equivalent to event per second 
IRB 
 
Institutional Review Board 
kHz 
 
kilohertz (equivalent to one thousand events per second) 
μC/cm2 Microcoulomb per square centimeter (units of charge density) 
μs 
 
Microseconds (equivalent to one millionth of a second) 
mA 
 
Milliamperes (equivalent to one thousand of an ampere) 
ms 
 
Milliseconds (equivalent to one thousand of a second) 
NPRS 
 
Numerical Pain Rating Scale 
PI 
 
Principal Investigator 
PM-SCS 
Polymodal Spinal Cord Stimulation 
PW 
 
Pulse Width of pulsed electric signal (in units of time) 
SAE 
 
Serious Adverse Event 
SCS 
 
Spinal Cord Stimulation 
ST 
 
Sensory Threshold 
UADE  
Unanticipated adverse device effects 
 
US-FDA United States Food and Drug Administration 

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1. 
BACKGROUND/SCIENTIFIC RATIONALE 
1.1  
Spinal Cord Stimulation Therapy and Chronic Pain 
  
It is estimated that about 20% percent of the population worldwide is affected by 
moderate to severe chronic pain1. Chronic pain becomes a burden to the individual as this affects 
a person’s ability to carry out many daily life activities, such as exercising, walking, driving a car, 
attending social events, or performing household chores.1 In the United States, chronic pain is 
considered one of the most pervasive and intractable conditions affecting at least one third of 
the population at an estimated cost of five hundred billion dollars per year, when combining 
health-related expenditure and the cost-impact on loss of productivity and income.2 
 Spinal cord stimulation (SCS) is a proven therapy that have been in use for over 40 years 
for various types of neuropathic pain and is a reversible, less invasive therapy that allows patients 
to evaluate the therapy for several days using an external stimulation (ENS) prior to receiving an 
implantable pulse generator (IPG).3,22,25,28 Conventional medical management, including 
medication and physical therapy, is often not adequate for treating chronic pain. In some cases, 
surgical interventions also fail to remediate severe cases of neuropathies and intractable back 
pain. Spinal Cord Stimulation (SCS) utilizes a pulsed electric field that is applied to the dorsal 
section of the spinal cord via electrode arrays, called leads, implanted in the epidural space.3 
Conventional (also called tonic) SCS utilizes an electric field oscillating in the 40-250 Hz frequency 
range. The electric field stimulates neurons that induce a tingling sensation (paresthesia) that is 
steered by the clinician and patient to overlay with the targeted pain location by modifying the 
applied electric field. This therapy has been clinically utilized for about half a century. The mode 
of action is based on the Gate Control Theory formulated by Melzack and Wall,4 although a full 
understanding of the mechanism has yet to be elucidated. The concept behind tonic SCS is that 
the paresthesia induced by the applied oscillating electric field masks (or “closes the gates to”) 
pain signals travelling to the brain.  
In recent years, new modalities have been developed in which the stimulation is done 
effectively and safely with pulses oscillating at frequencies larger than conventional ones (i.e. 
1,200 Hz) including high frequency (10 kHz),5,6,7 as well as oscillating bursts of pulses (5 pulses at 
500 Hz).8,9 A unique aspect of these treatments is that pain may be relieved without the need of 
the often uncomfortable paresthesias.  
There are currently various Spinal Cord Stimulation (SCS) systems which have received CE 
mark and are approved by the FDA for use in the U.S. These devices are indicated as a sole 
mitigating agent or as an adjunct to other modes of therapy used in a multidisciplinary approach 

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for chronic intractable pain of the trunk and/or limbs, including unilateral or bilateral pain 
associated with failed-back surgery syndrome, intractable low back pain and leg pain. 
1.2  
Scientific Rationale 
A pilot animal study carried out in our laboratory indicates that it may be possible to 
combine stimulation parameters commercially available to obtain pain relief. The term 
polymodal spinal cord stimulation (PM-SCS) is used in this document to describe this therapy. 
PM-SCS consists of simultaneously applying pulsed oscillatory electric fields to different arrays of 
electrodes in the implanted leads. One of the stimulation fields is referred to as the priming field. 
This priming field prepares the neural structure for a more efficient stimulation with the other 
electric field(s). It is well known that the impedance of neural tissue can be decreased with an 
applied electric field.10,11 This increase of the permeability of the tissue to current induced by the 
priming field reduces the amount of current required for neuronal depolarization.12 The priming 
field also contributes to neuronal desynchronization, which is a mechanism that helps with the 
reestablishment of neuronal circuits that have been unnaturally synchronized to maintain a 
nociceptive input into the brain.13 Additional beneficial effects may be related to the modulation 
of genes and proteins as a result of the proper choice of electrical currents provided by the 
polymodal SCS therapy, as shown by recently published work.14,15 Neural tissue is constituted by 
neurons and glial cells. Glial cells are known to play an important role in the maintenance of 
chronic pain as they regulate the homeostasis of excitatory and inhibitory neurotransmitters in 
the synaptic cleft.16 Chronic pain is related to a process called central sensitization which results 
from changes in the synapses of sensory neuronal networks along the nociceptive pathway.17 It 
is also known that glial cells can respond, although quite different than neurons, to applied 
electrical fields.18,19,20 The combination of electrical fields may provide a manner to discriminately 
stimulate both cell populations in such a way that glial cells may be driven to homeostatic state 
that reestablishes proper synapse plasticity, while neurons are driven to firing patterns that 
reduce painful sensations. Therefore, the utilization of polymodal SCS offers an opportunity to 
provide better pain relief than that obtained with tonic SCS while using stimulation parameters 
that have been proven to be safe for human use.     
 
1.3  
General Description of a Trial Stage for Spinal Cord Stimulation Therapy 
 
SCS therapy may not be suitable for all patients that suffer intractable chronic pain 
conditions. In order to assess if a patient qualifies for SCS therapy, they must be enrolled in a trial 
stage as prescribed by a physician. The beginning of the trial stage period involves the 

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implantation of the trial leads and initial programming of therapy. A trained physician introduces, 
percutaneously, a set of trial leads within the epidural space along vertebral levels appropriate 
to stimulate segments of the spinal cord associated to the painful dermatome. The leads are 
connected to a commercial external neurostimulator (ENS) that is programmed by a clinician to 
deliver pulsed oscillatory signals to particular sets of electrodes in the leads using parameters 
that provide pain relief within an established safety range. A pulsed electric signal is characterized 
by three parameters: pulse frequency (F), pulse width (PW), and amplitude (A). The ENS allows 
the clinician to set various therapy options to be tried by the patient during the SCS trial stage 
period. A signal with a specific combination of parameters (F, PW, A) that is delivered to a specific 
array of electrodes in the leads is called a program.  A combination of programs, called a group, 
constitutes a therapeutic SCS option to be tried. The patient is discharged from the clinic with an 
active therapy group and the clinician would follow up and may instruct the patient to select a 
different therapy group, which may provide better pain relief. At the end of the trial stage, the 
physician and patient assess the level of pain relief as well as the level of comfort of the patient 
with the treatment received by one or various therapy groups. The temporary leads are then 
removed from the patient. If the trial stage is considered successful, then the patient may return 
for surgical implantation of permanent leads and an implantable programmable stimulator 
device.  
Programming with PM-SCS will occur during the trial stage period after the patient has 
undergone a trial of the therapy using conventional SCS. PM-SCS will utilize the same trial leads, 
interface trial cable, and remote controller that had been used during the conventional SCS 
period. The leads, interface trial cable and remote controller are commercial products (i.e. FDA 
approved). The ENS for PM-SCS is an investigational device based on a commercial platform 
which has been modified and tested to safely provide programs and therapy groups with the 
proper parameter sets (F, PW, A). The patient will try conventional SCS therapy at the beginning 
of the trial stage period for up to five days and then, after a brief washout period, will receive 
PM-SCS therapy for up to five days.     
2. 
RISKS AND BENEFITS 
SCS have been used therapeutically since 1967.21 Over the years, SCS has been proven to be 
effective and safe, and to improve the quality of life of thousands of patients suffering from 
chronic pain who have failed other treatments, including conservative therapies (i.e. 
pharmacological, physical therapy) and surgery.22  
2.1  
Risks 

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It is anticipated that stimulation programs used when administering PM-SCS therapy will 
exhibit a safety profile equivalent to that exhibited by a stimulation programs used during 
conventional SCS therapy, considering that the ENS used is based on a commercially available 
platform which has been cleared by CE mark and approved by the US-FDA. It is anticipated that 
no additional risk is introduced with the treatment with polymodal SCS. 
• PM-SCS has been tested in small laboratory animals without any adverse events.  
• Other investigators have utilized frequencies up to 10 kHz or waveforms for SCS 
treatment with comparable or substantially similar profile adverse events.5,6,7,8,9,23   
• The procedure will use commercially available trial leads, interface trial cables, and 
patient remote controller that are currently used in standard clinical practice during 
trial stimulation periods. The ENS is also based on a commercial unit, and can only 
deliver CE-Mark and FDA approved parameters. These components have been tested 
to meet quality standards by the manufacturer of the device for safe operation.  
• It is anticipated that any complications that result when using the PM-SCS therapy 
would be similar to those already identified when using conventional, high frequency, 
and burst therapies during a standard SCS trial period. 
• The system is designed to prevent tissue damage. Electrical signals delivered by the 
ENS are charged balanced with a biphasic waveform as with other commercially 
available SCS systems. The amount of charge density per pulse per phase to be used 
during programming with two signals is well below the recognized maximum level (40 
μC/cm2) for safe energy delivery in neural tissue,24 and comparable or below that 
utilized during conventional SCS, high frequency SCS and burst SCS.  
There is a substantial body of evidence that indicates that SCS is safe and that serious adverse 
events are rare, while most common complications can be resolved with minor interventions. 
This large body of evidence has stimulated professional societies such as the International 
Neuromodulation Society (INS) and the American Society of Interventional Pain Physicians 
(ASIPP) to commission a body of experts to review the available body of evidence and provide 
recommendations intended to be a guide for proper and safe practice of SCS therapy.22,25,26 This 
study will follow these guidelines.    
Complications of SCS therapy have been previously reviewed and listed in Table 1.25,26,27,28,29 
These are associated with the implantation of the temporary leads and include superficial 
infection, deep infection, dural puncture with associated comorbidities, epidural hematoma, and 

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spinal cord damage. Dural puncture is a well-known complication with any procedure that 
accesses the epidural space. A significant post-dural puncture headache would be treated with 
fluids, analgesics, and bed rest; while a recalcitrant one may require an epidural blood patch.      
Unlikely risks and complications associated to the leads include pain at the implant site, and 
tissue reaction to leads. Serious complications such as paralysis, nerve injury and death are very 
unlikely risks. 
Possible risks associated with stimulation include malfunctioning of the ENS, undesirable 
sensations, increased pain (other than at implant site), uncomfortable stimulation of muscle and 
skin, and development of pain symptoms in a new location. Unlikely risks include an increase in 
the intensity, duration, or frequency of pain to be treated. Seizures, paralysis, nerve injury or 
death are very unlikely to occur as a result of stimulation.  
Electromagnetic interference (EMI) is a field of energy generated by equipment that can be 
found in medical, work, home or public environments and that is strong enough to interfere with 
the device function. Both the commercial and investigational devices (ENSs) used in this study 
include features that has been tested to provide protection from EMI. Most electrical devices and 
magnets encountered by a patient in a normal day are unlikely to affect the operation of the ENS 
or remote controller. However, sources of strong EMI can result in the following adverse events: 
serious injury or death, lead migration, operational changes of the device, and unexpected 
changes in stimulation therapy. In order to minimize the risk of EMI, patients will be instructed 
to avoid exposure to defibrillators, diathermy based therapies, electrocautery, arc welding, 
power stations, magnetic resonance imaging (MRI), radiofrequency (RF) or microwave ablation, 
bone growth stimulators, electrolysis, therapeutic ultrasound, ultrasound, lithotripsy, 
psychotherapeutic procedures, radiation therapy, theft detectors, therapeutic magnets, and 
transcutaneous electrical nerve stimulators. Patients that may require the use of certain 
therapies or devices that generate strong EMI during the study will not be admitted to 
participate. Patients with other active implanted devices will not be admitted in the study. 
In summary, the study has been designed to minimize the potential for injury to the subject. 
The procedures used in this study are all routine medical procedures using standard products as 
aforementioned. Also, the list of exclusion criteria includes a few that will mitigate the risk of EMI 
or mishandling of the devices by potential patients. The potential risks for this study are identical 
to risks seen with standard commercially approved SCS systems. Following standard practices of 
care, subjects will be trained and educated about avoiding or minimizing their exposure to EMI, 
proper operation of the device and remote control, and to contact the investigators when they 
suspect a complication.  

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All procedures, including implantation and programming, will be conducted by experienced 
and properly trained personnel following routine medical procedures and standard techniques, 
which would make the risks associated with this study to be the same as the risks associated with 
commercially approved SCS systems.  
Table 1. Risks associated with SCS therapy 
Type of Risk 
Level of Risk 
Risk and Occurrence 
Lead Implant Risks 
Possible 
Lead migration (13.2%) 
 
 
Failure/malfunction of leads (9.1%) 
 
 
Superficial site infection (4.5%) 
 
 
Procedure complications, including infection & fever (3.4%) 
 
Unlikely 
Persistent pain at lead implant site (0.9%) 
 
 
Temporary pain at implant site (0.9%) 
 
 
Tissue reaction to leads (0.3%) 
 
 
Epidural hematoma (0.3%) 
 
 
Skin erosion around the leads (0.2%) 
 
Very Unlikely 
Allergic reaction to leads (0.1%) 
 
 
Paralysis (0.003%) 
 
 
Nerve injury 
 
 
Death 
Stimulation Risks 
Possible 
Malfunction of stimulation system (4.5%) 
 
 
Undesirable sensations (2.4%) 
 
 
Increased pain in area other than implant site 
 
 
Uncomfortable stimulation of tissue around leads 
 
 
Development of pain in a new location 
 
Unlikely 
Increase in pain intensity, duration, or frequency 
 
Very Unlikely 
Seizure 
Paralysis 
Nerve injury 
Death 
2.2  
Benefits: 
Because of the short-term of the study, there is no opportunity for long-term benefits to 
patients in this study beyond those associated with the outcome of the trial of conventional SCS 
therapy. A patient that experiences a successful outcome with trialing conventional SCS therapy 

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will be eligible for a permanent implant. Participation in this study will provide information that 
will add to our understanding of treatment options for patients with back pain. 
 
3.  
OBJECTIVES 
3.1  
Purpose: 
To determine the feasibility of polymodal spinal cord stimulation therapy in patients with 
chronic intractable lower back pain with or without leg pain. 
 
 
3.2  
Objective: 
To demonstrate that spinal cord stimulation using multiple simultaneous waveforms 
provides pain relief in patients suffering chronic intractable low back pain with or without leg 
pain. 
 
3.3  
Primary endpoint: 
 
3.3.1  Back pain score reduction relative to baseline pain score (i.e. prior to SCS) at day 
5 post-initiation of a particular SCS therapy (conventional or polymodal).  
 
 
 
 
 
3.4 
Secondary endpoints: 
 
3.4.1  Percentage change relative to baseline back pain (i.e. prior to SCS) at day 5 post-
initiation of a particular SCS therapy (conventional or polymodal) 
3.4.2 Responder rate to therapy, defined as the number of patients that were successful 
with therapy relative to the total number of patients receiving therapy. Success of 
therapy is defined as a 50% or more reduction in back pain. 
3.4.3 Patient subjective evaluation of whether a patient experienced paresthesia with 
PM-SCS or not.  
3.4.4 Patient subjective satisfaction with PM-SCS and conventional SCS and therapy of 
choice.  
3.4.5 Incidence of adverse events. 
 

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4. 
ELIGIBILITY 
4.1  
Inclusion Criteria: 
4.1.1 Capable of giving written informed consent to participate in this clinical study 
based on voluntary agreement after a thorough explanation of the patient’s 
participation is provided to them. 
4.1.2 Chronic intractable pain of the lower back equal to or greater than pain in lower 
limbs, and that has been refractory to conservative therapy for ≥ 3 months 
4.1.3 Must be older than 18 years old. 
4.1.4 Average back pain intensity of ≥ 5 out of 10 on the numerical pain rating scale 
(NPRS) 
4.1.6 Appropriate candidate for spinal cord stimulation trial  
4.1.7 Subjects must be on a stable dose of pain medication regimen for at least one 
month. 
4.1.8 Female patients who are not pregnant and do not plan to become pregnant 
during the study.  Females of child bearing potential must provide a negative 
pregnancy test and must be using reliable contraception and must continue to 
use reliable contraception until study completion.  Non-childbearing potential is 
defined as postmenopausal for at least 2 years or surgical sterilization or 
hysterectomy at least 3 months before study start. Patients who become 
pregnant or who have a spouse/significant other that becomes pregnant during 
the course of this study agree to report pregnancy to the study physician/staff 
4.1.9 Must be able to comply with the requirement of study visits and follow-up and 
phone visits 
4.1.10 Have cognitive ability of operate the remote control and follow therapy 
instructions and directions by investigator 
4.2  
Exclusion Criteria: 
4.2.1 Systemic infection 
4.2.2 Any active implanted device 
4.2.3 Previous experience with SCS therapy either during a trial or fully implanted 
4.2.4 Evidence of serious neurological, psychological or psychiatric disorders. 

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4.2.5 Mechanical spinal instability 
4.2.6 Patients with uncorrected coagulation disorders or who are on anticoagulation 
therapy and cannot interrupt the therapy 
4.2.7 Patient who are pregnant, breast-feeding or women of childbearing potential with 
positive pregnancy tests   
4.2.8 Human immunodeficiency virus (HIV) infection or a clinically significant infection 
4.2.9 Patients who are undergoing or will undergo therapies or diagnostics that involve 
electromagnetic fields such as: diathermy based therapies, electrocautery, 
magnetic resonance imaging (MRI), radiofrequency (RF) or microwave ablation, 
bone growth stimulators, electrolysis, therapeutic ultrasound, ultrasound, 
lithotripsy, psychotherapeutic procedures, radiation therapy, and transcutaneous 
electrical nerve stimulation.  
4.2.10 A clinically significant disorder such as cerebrovascular disease, pulmonary 
infarction, ischemic heart disease, cardiac dysrhythmia, myocardial infarction, or 
congestive heart failure or any other as determined by the investigator 
4.2.11 Uncontrolled diabetes, uncontrolled pulmonary disease, or uncontrolled 
hypertension 
4.2.12 Patients who have evidence of major psychiatric disease, mental disorder, drug 
dependency, alcohol dependency, or substance abuse disorders 
4.2.13 Patients who have progressive neurological disease such as multiple sclerosis, 
chronic inflammatory demyelinating polyneuropathy, rapidly progressive 
arachnoiditis, acute herniated disc, or any other as determined by investigator  
4.2.14 Medical condition or pain condition in other body areas that could interfere with 
study procedures, accurate pain reporting, and/or confound evaluation of study 
end points 
4.2.15 Concurrent participation in another clinical study 
4.2.16 Involvement in an injury claim under current litigation or a pending or approved 
workers’ compensation claim 
4.3  
Withdrawal: 
Subjects may voluntarily withdraw from the study at any time. Withdrawing from the trial 
will not carry out any sanction and will not affect patient’s access to other treatments. 
4.4  
Terminating Participation: 

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A patient’s participation in the study may be terminated if continued participation in the 
study is not in the subject’s best interest, according to the Principal Investigator’s opinion or if 
the subject withdraws participation from the study. Therapy will be stopped and leads will be 
removed. Any patient who suffers an adverse event whether or not related to study treatment 
may withdraw voluntarily from the study.  
5. 
DESIGN AND PROCEDURES 
5.1  
Study Design 
 
 
This is a prospective, observational cross-over study that will compare conventional SCS 
and polymodal SCS during two different time windows during an SCS trial period. Up to 25 
patients will be included in the study. Figure 1 illustrates a general diagram of the study process. 
A screening/enrollment visit will assess the eligibility of a potential subject who has already given 
adequate time to evaluate and discuss the informed consent form. Patients that meet all the 
inclusion and exclusion criteria and who reaffirm voluntary informed consent to participate in 
the study will be enrolled. Patients enrolled in the study will visit the clinic to start the SCS trial 
period which involves the implantation of the stimulation leads and programming of 
conventional SCS therapy. Conventional SCS therapy will be administered before PM-SCS therapy 
for 4 ± 1 days. It is not possible to completely blind the patient and clinicians interacting with the 
patient from conventional SCS or PM-SCS, because conventional SCS requires paresthesia (i.e. a 
sensory effect), which is expected to be absent with the PM-SCS.  
 
 
 
  
 
Figure 1. Flow diagram of the study process. 
 

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After the patient has trialed conventional SCS therapy, there will be a washout period which 
is expected to last no more than one day. This will allow analgesic effects of the conventional 
therapy to wear off. The patient will visit the clinic to crossover to PM-SCS therapy and will trial 
it for 4 ± 1 days. After the trial period is over, the implanted temporary leads will be disconnected 
from the ENS and removed from the patient and the trial period will end. The trial period during 
the study will not extend longer than ten days. Table 2 shows a schedule of events. 
Table 2. Schedule of Events. 
 
 
Event\Activity 
Enrollment/
Baseline 
(Day 0) 
Start of SCS Trial 
(0-30 days after 
enrollment/baseline) 
Crossover to 
Polymodal SCS 
(3-5 days after 
start of trial) 
End of Study 
(3-5 days after 
crossover to PM-SCS) 
Informed Consent 
X 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
Pregnancy TestA 
X 
 
 
 
General Health and 
Pain Medications  
X 
 
 
 
Pain NPRS 
X 
 
X 
X 
Informed Consent 
Reaffirmation 
X 
 
 
 
Lead Implantation 
 
X 
 
 
X-ray Fluoroscopy 
 
X 
X 
X 
Programming of 
Conventional SCS and 
start of trial 
 
[X] 
 
 
Programming of PM-
SCS 
 
 
[X] 
 
Stimulation Sensation 
Assessment 
 
 
 
 
X 
Impression of 
Improvement and 
Patient Satisfaction 
 
 
 
 
X 
Adverse Event 
Assessment 
 
X 
X 
X 
A Administered only to subjects of childbearing potential 
[X] Optional reprogramming (conventional or polymodal SCS) visits are allowed at the discretion of the 
investigator and depending on the feedback from standard of care follow up phone visits.  

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5.2  
Recruitment and Consent: 
 
The investigator will discuss participation in the study with a patient who is already 
qualified and approved for a SCS therapy trial and who may qualify to be enrolled in the study 
according to inclusion and exclusion criteria. The patient will be given the opportunity to read an 
informed consent form (ICF) and get answers to all questions before consenting participation 
(see Appendix A for details on the Informed Consent Process).  
 
5.3  
Clinic Visit 1: Enrollment/Baseline Visit 
 
A patient will be enrolled in the study upon signing the ICF, verifying that all inclusion 
and exclusion criteria are met (using CRF01) and reaffirming voluntary participation, and. 
Medical history, including pain management, and baseline pain will be collected and recorded 
in the appropriate CRFs (CRF02, CRF03, and CRF04).    
 
5.4  
Clinic Visit 2: Lead Implantation, Conventional SCS Programming and Training 
Procedure: 
 
Patients will be implanted with commercially available temporary leads as part of the 
regular SCS trial period and using standard clinical practice. The patient will be placed on a 
surgical bed in a supine position and may be mildly sedated. The back of the patient will be 
draped and cleaned using sterile techniques. A properly trained physician will guide and place 
two percutaneous leads into the epidural space using introducers and steering stylets while 
under fluoroscopic x-ray guidance. Once the leads are placed above the dorsal aspect of the cord 
at the proper vertebral level, the introducers and stylets are removed. The exterior portion of 
the leads will be anchored with sutures or taped firmly to the skin and the proximal ends of the 
leads connected to an interface cable, which will be plugged into the ENS. The leads and cables 
will be properly secured to minimize migration of the leads and prevent accidental disconnection. 
An AP and lateral radiograph of the implanted leads in reference to the vertebral levels will be 
collected. After the patient has recovered from sedation, programming of conventional SCS 
therapy will be performed using standard clinical practice.  
 
5.4.1 Conventional SCS Therapy:  
For Conventional SCS Therapy, the ENS will be programmed to deliver pulses at a 
frequency in the 20-200 Hz range with a maximum pulse width of 1 ms. The amplitude of 

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the electrical signal and the arrays of electrodes used for delivering therapy will be set in 
order to elicit paresthesia as reported by the patient. Once paresthesia is reported, this 
will be used to guide the programmer to cover the proper pain dermatome. These 
parameters and electrode arrangements will be noted and saved in the remote controller. 
The patient will be educated and trained on operation and troubleshooting the ENS and 
remote controller. 
 
Following a satisfactory demonstration on ENS and remote controller operation, the 
patient will be discharged to home with an emergency 24-hour contact information should 
the patient have any issues or questions. Programming and training procedure should be 
approximately 1.5 to 2 hours long. The patient will be scheduled to return to the clinic for 
the crossover reprograming visit 4 ± 1 days after the initial programming.  
 
5.5  
Clinic Visit 3: Crossover visit: 
 
After 4 ± 1 days of trialing conventional SCS therapy, the patient will return to the clinic 
for a reassessment of the lead location using x-ray fluoroscopy, and crossover to PM-SCS therapy. 
Pain level obtained with conventional SCS will be assessed and recorded in CRF05 before crossing 
over to PM-SCS therapy.  The study physician may reposition the leads if deemed necessary upon 
comparison to the initial x-ray image. If leads have migrated and cannot be re-adjusted, the 
patient will be exited from the study and subject data will be excluded from the final analysis. 
After x-ray assessment, stimulation parameters will be programmed as described below for PM-
SCS. No therapy will be given for up to one day to allow washout of the conventional SCS therapy.  
 
5.5.1 Polymodal SCS Therapy:  
 
In this case the ENS will be programmed to deliver multiple simultaneous signals with 
different stimulation parameters to different electrode arrays in the leads. Stimulation 
signals will be in the 20-1,200 Hz range and a maximum pulse width of 1 ms, which is 
within the CE Mark and FDA approved parameters. The parameters of each program will 
be saved in the remote controller. The patient will be educated and trained on operation 
and troubleshooting the ENS and remote controller as it pertains to PM-SCS therapy. 
 
5.6  
Standard of Care Follow up phone visits: 
 
It is standard practice that during a SCS trial period, a Clinical Field Technician (CFT) will 
contact the patient by phone to track the status of therapy and comfort of the patient. 

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Accordingly, follow up phone visits will be performed as needed during the study. After the first 
day of therapy and depending on the extent of pain relief reported by the patient, the CFT may 
instruct the patient to adjust the level of stimulation as deemed appropriate by patient to obtain 
optimum pain relief. The patient may also be instructed to use a different therapy group in case 
a therapy cannot be optimized with the previously tried therapy group. This process may be 
repeated during trial days for both the conventional SCS part of the trial and the PM-SCS part of 
the trial. Depending on feedback from the phone visits, the PI may decide to schedule a visit to 
the clinic for reassessing lead position and reprogramming, or to address an adverse event. 
 
5.7  
Optional unscheduled clinic visit: 
 
If lead migration is suspected, the PI may schedule a reprogramming visit. In this visit, the 
PI may evaluate the position of the leads inside the epidural space using x-ray fluoroscopy and 
reposition and/or reprogram as needed. The PI may also change stimulation parameters using 
patient feedback as done during the initial visit or during the crossover visit. This visit may also 
be used to address any other mild or moderate adverse events related to SCS therapy. 
 
5.8  
Clinic Visit 4: End of trial period visit: 
 
The patient will return to the clinic as scheduled for an end of trial period visit, in which 
the stimulation will be stopped, the hardware disconnected from the leads, and the temporary 
leads removed. Before stimulation is stopped, the patient will be asked to provide feedback 
about pain status, subjective satisfaction, and paresthesia sensation, which will be recorded in 
the appropriate CRFs (CRF06, CRF07, and CRF08). This visit may take place any time if the PI 
deems necessary to exit a patient from the trial and study, or if the patient voluntarily decides to 
withdraw.  
 
5.9 
Other therapies: 
 
As per standard of care practice the patient may continue on prophylactic antibiotics as 
prevention for bacterial skin infection. Patient will also follow the investigating physician’s 
protocol for anticoagulant therapy, other medications, as well as over-the-counter medications 
and supplements.  
 

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6. 
DATA COLLECTION AND ANALYSIS 
6.1  
Effectiveness: 
A statistical analysis based on analysis of variance will be carried out. Given that this is an 
early-stage observational study, with a small population size, the analysis may not provide 
appropriate power and significance of endpoint measurements. Standard statistical analysis 
including the number of observations, mean, ranges for quantitative variables and relative 
percent for some categorical variables will be reported as appropriate. 
During and at the end of the trial stage, patients will be asked to provide feedback 
regarding sensations and pain relief as a result of the polymodal stimulation therapy and in 
comparison with conventional therapy. 
Pain intensity will be rated using the numerical pain rate scale (NPRS). Patients will score 
the severity of pain using this 11-point scale, with zero (0) indicating no pain and ten (10) 
indicating the worst pain imaginable. The patient will be asked to evaluate the average level of 
pain experienced during a particular time window between visits. The primary endpoint of record 
will correspond to the average NPRS score reported at the end of each therapy period. Patients 
will serve as their own control.  
6.2  
Paresthesia, Patient Impression, and Satisfaction 
At the end of the trial period, patients will also be asked about their paresthesia 
experience, therapy preference, and their global impression of improvement and satisfaction. 
Questionnaires will be administered for such effects.  
6.3  
Safety 
Adverse events (AE) related to the stimulation therapies will be tracked during the study 
period to address any safety outcomes. Any AE encountered using the conventional SCS therapy 
will also be noted in the patient’s medical history. All device and/or procedural adverse events 
will be reported. 
AEs will be tracked and categorized by the PI as related to implant (leads) or activation of 
the stimulation program. It is expected that the polymodal SCS will have a safety profile similar 
to conventional SCS. 

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All AEs will be recorded in the corresponding Case Report Form (CRF). The PI will also rate 
the AE in terms of its severity. Any AE considered by the PI to be a serious adverse event (SAE) 
will be reported immediately (within 24 hours) to the sponsor and to the IRB within five (5) days 
after the PI first learns of the event. 
6.3.1  
Adverse Events (AEs): 
The following is a list of potential adverse events associated to SCS therapy and the 
indwelling leads with reported risk and frequency of occurrence: 
• Related to Lead implant: 
o Movement of lead (possible, 13.2%) 
o Malfunction or failure of lead (possible, 9.1%) 
o Superficial site infection (possible, 4.5%) 
o Complications related to implantation procedure including infection; fever 
(possible, 3.4%) 
o Persistent or temporary pain at the implant site (unlikely, 1.8%) 
o Tissue reaction to leads (unlikely, 0.3%) 
o Hematoma (unlikely, 0.3%) 
o Bleeding (unlikely, 0.3%) 
o Skin erosion over the leads (unlikely, 0.2%) 
o Allergic reactions to leads (very unlikely, 0.1 %) 
o Paralysis (very unlikely) 
o Nerve injury (very unlikely) 
o Death (very unlikely) 
• Related to stimulation: 
o Malfunction of stimulation system (possible, 4.5%) 

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o Undesirable sensations (possible, 2.4%) 
o Increased pain (possible) 
o Uncomfortable stimulation of tissue around the leads (possible) 
o Development of pain symptoms in a new location (possible) 
o Increase in pain intensity, duration, or frequency (unlikely) 
o Seizure (very unlikely) 
o Paralysis (very unlikely) 
o Nerve injury (very unlikely) 
o Death (very unlikely) 
AEs related to stimulation with the trialed therapy are expected to be comparable to 
those associated to others encountered with other SCS therapies (such as HF-10 or Burst) or 
ENS.  
At each evaluation the PI will determine whether any AE have occurred, keeping in mind 
that an AE is any undesirable medical occurrence in the patient. If it is determined that an 
AE has occurred, the PI should obtain all information required to complete the AE form of 
the CRF (CRF09). Patients should also be encouraged to contact the PI if any significant AEs 
occur between visits. 
6.2.2  Serious Adverse Events (SAEs): 
All serious SAEs must be reported to the sponsor (or designee) and IRB within 24 hours 
after the PI first learns of the event and to the IRB within 5 days after the PI first learns of 
the event. An adverse event is considered serious if: 
• Leads to death 
• Leads to a serious deterioration of the health of the patient that results in: 
o Life-threatening illness or injury 
o Permanent impairment of a body structure or body function 

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o Inpatient hospitalization or prolongation of existent hospitalization 
o Medical or surgical intervention to prevent permanent impairment to body 
structure or body function 
All SAEs will be followed until the event is resolved. The PI will decide if additional follow 
up information is needed in case the event is not resolved at study completion. In case of 
death, all possible information available, e.g. autopsy or other post-mortem findings, 
including the possible relationship to the procedure or treatment should be provided. 
6.2.3  Unanticipated adverse device effects (UADEs): 
Unanticipated adverse device effects are defined as serious adverse effect on health or 
safety, or any life-threatening problem or death caused by, or associated with a device, if 
that effect, or problem, or death was not previously identified in the protocol.   
The PI must submit to sponsor (or designee) any UADE within 24 hours after the PI first 
learns of the effect. The PI must also report the UADE to the IRB according to local 
regulations. 
7. 
DEVICES 
7.1  
Stimulation leads:  
Commercially available SCS leads will be used. Since leads are manufactured with variable 
dimensions and number of electrode arrays, the study will utilize leads with the following 
specifications in order to avoid outcome variability. The patient will be implanted with two in line 
eight-contact percutaneous cylindrical leads, each with a diameter of 1.3 mm, an edge-to-edge 
inter-electrode distance of 6 mm or 4 mm, and an electrode length of 3 mm. These specifications 
are met by leads available from Medtronic (Minneapolis, MN, USA; Reference 3873 1x8 Standard 
or 3874 1 x 8 Compact). The same leads will be used during both conventional and polymodal 
SCS therapy.  
7.2  
Multi-lead trialing cable: 
The proximal end of each lead is terminated by eight metal contacts that deliver electrical 
signals to the electrodes in the distal end. These contacts are interfaced to an ENS unit using a 
cable that is fully compatible with both the stimulation leads and ENS unit. A commercially 

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available cable from Medtronic (Minneapolis, MN, USA; Reference 355531) will be used. The 
same cable will be used during either conventional or polymodal SCS therapy.  
7.3  
External Trial Stimulator (ENS) unit:  
The trialing cable is connected to the ENS unit which is the device that delivers the 
stimulating electrical signals. A commercially available external trial neurostimulator from 
Medtronic (Minneapolis, MN, USA; Reference 37022) will be used during the conventional SCS. 
An investigational device based on this commercial unit will be used for PM-SCS (Medtronic, 
Minneapolis, MN, USA; Reference 37022-MRS). This ENS is designed to safely deliver biphasic 
charge-balanced electrical pulses in the frequency range 2 to 1,200 Hz with pulse width in the 60 
to 1,000 μs range and amplitudes in the 0 to 21 mA range with 0.1 mA resolution, identical or 
similar to other commercially available devices. Upper limits are set using firmware in order to 
guarantee safe operation with the particular combinations of parameters required for each 
therapy. Refer to Appendix D1 for a product description and labeling of the investigational ENS. 
7.4 
 Clinician Programmer:  
The ENS unit is programmed by a trained CFT using a computer-based interface and 
software. The programmer is fully compatible with the ENS unit described above and uses short-
distance telemetry protocols to safely communicate with the ENS unit. For conventional SCS, 
commercially available N’Vision® Clinician Programmer (Medtronic, Minneapolis, MN, USA; 
Reference Model 8840) will be used by the CFT or clinician to program the commercial ENS unit.  
For PM-SCS, a Multi-Rate Stimulation (MRS) researcher programmer system (Medtronic, 
Minneapolis, MN, USA; Reference NRP1107-40668) available in a commercial laptop computer 
will be used by the CFT or clinician to program the ENS unit. Refer to Appendix D1 for a product 
description. 
7.5 
 Patient Remote Controller:  
Spinal cord stimulation therapy (either conventional SCS or PM-SCS) can be adjusted by 
the patient using the parameters set by the clinician during programming. This can be done using 
a handheld device that communicates with the ENS via short-distance telemetry. The remote 
controller allows the patient to turn the therapy on or off, adjust the level of stimulation (i.e. the 
amplitude of the electric field), and switch from a therapy group to other one as previously set 
by the CFT and clinician. The patient remote controller is fully compatible with both the ENS, and 
the clinician programmer described above. A commercially available device from Medtronic 
(Minneapolis, MN, USA; Reference MyStim® 97740) will be provided to the patient to carry on 
during the trial. The CFT will train the patient on using the remote controller and will provide 

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printed operating instructions as well as contact information in case the patient should have any 
questions about operating the device. Refer to Appendix D2 for a detailed product description. 
7.6 
 Device Accountability Procedures:  
All non-disposable devices (ENS, patient remote controller, and clinician programmer) will be 
under the control of the CFT who will program the ENS once the leads have been attached to it. 
The serial numbers of the investigational ENS and remote controller will be annotated in the 
corresponding CRF (CRF10). The CFT will be available 24-hours a day at a location near the 
study site during the length of the therapy. The CFT will retrieve the devices once a subject has 
completed therapy or exited the study. No devices will be left in the custody of the study site; 
thus study sites will not carry an inventory of devices.  
Use of an investigational device outside the described study protocol is strictly forbidden and 
will constitute grounds for removal of the operator or institution from the study. 
 
8. 
CONDUCT OF STUDY 
8.1  
Statement of Study Compliancy: 
The study will be performed in accordance with Good Clinical Practice (GCP) guidelines 
and recommendations guiding physicians in biomedical research involving humans. As required 
by IRB timelines, the PI is responsible for reporting annually a study progress to the IRB. The 
PI/sponsor, as required by local regulations, is required to report in writing to the IRB, notice of 
completion, termination, or discontinuation of the study. If the study is discontinued for safety 
concerns, the PI will notify the IRB immediately.  
8.2  
Sponsor: 
StimGenics will serve as the Sponsor of the study.  It is the responsibility of StimGenics     
as the Sponsor of the study to ensure proper monitoring of the investigation and to see that all 
the clinical requirements are met.  The study will be conducted under GCP guidelines and 
applicable regulatory requirements. All data used in the analyses and reporting of this 
investigation will be coded without identifiable reference to the subject. Access to confidential 
and private files will be given to only authorized personnel and representatives of the Sponsor 
and regulatory authorities as required.  

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8.3 
Monitoring Activities: 
 
Stimgenics will assign a contract research organization (CRO) to conduct monitoring 
activities of the study according to a monitoring plan. The monitoring plan will facilitate 
compliance with GPC guidelines and other relevant guidelines. The CRO will assign qualified 
monitors to verify that: 
• The rights and well-being of participants are protected 
• Reported data are accurate, complete and verifiable from source documents 
• The study is conducted in compliance with currently approved protocol and other 
applicable regulatory requirements 
The monitoring plan identifies key monitoring activities and specifies the data to be reviewed 
over the course of the clinical study. The clinical study monitors will conduct monitoring visits in 
accordance with this plan. 
 
8.4  
Quality Control and Quality Assurance: 
 
All documents and data will be produced and maintained in such a way to assure control 
of documents and data to protect the patient’s privacy as far as reasonably practicable. The 
Sponsor, CRO and representatives of regulatory authorities are permitted to access study 
documents (e.g. protocol, CRFs, medical records/files) as needed. All attempts will be made to 
preserve patients’ privacy and confidentiality. 
 
8.5  
Data Handling and Record Keeping: 
 
Source documents will be maintained by the PI. Data will be transcribed on to paper study 
CRFs and the original data will be secured by the PI and made available to Sponsor and CRO. PI is 
required to maintain records for a period of five (5) years. All CRFs pages will be subject to initial 
inspection for omitted data, data inconsistencies, illegible data and deviations by the monitoring 
body. All hard copies of CRFs and media will be stored in a secure location.  
 
PI is responsible for submitting data and reports as follows: 
• AEs: In an ongoing basis. This will be reported in the proper section of the CRF. 

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• SAEs or UADEs: Report within 24 hours of knowledge of event to Sponsor and report to IRB 
within five days as per their regulations. 
• Deviations, exceptions, violations of protocol: Report to Sponsor within 5 days and report to 
IRB per their regulations. 
• Protocol Progress report: Provide a copy to Sponsor and IRB as per regulations. 
• Study Closure report: Provide a copy to Sponsor and IRB as per regulations.  

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9. 
REFERENCES 
1. The Global Pain Therapeutics Market Analysis, R&D Pipelines and Competitive Landscape, 
Arrowhead Publishers, 2007, pp. 408. 
2. Institute of Medicine (US) Committee on Advancing Pain Research C, and Education. Relieving 
Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. 
Washington (DC): National Academies Press (US), 2011, pp. 2.  
3. Smits H, van Kleef M, Holsheimer J, et al. Experimental spinal cord stimulation and 
neuropathic pain: mechanism of action, technical aspects, and effectiveness. Pain Practice 
2013; 13:154-168.   
4. Melzack R, Wall PD. Pain mechanisms: A new theory. Science 1965; 150:971-979. 
5. Al-Kaisy A, Van Buyten JP, Smet I, et al. Sustained effectiveness of 10 kHz high-frequency 
spinal cord stimulation for patients with chronic, low backpain: 24-month results of a 
prospective multicenter study. Pain Medicine 2014; 15:347-354. 
6. Van Buyten JP, Al-Kaisy A, Smet I, et al. High-frequency spinal cord stimulation for the 
treatment of chronic back pain patients: results of a prospective multicenter European clinical 
study. Neuromodulation 2013; 16:59-65. 
7. Kapural L, Yu C, Doust MW, et al. Novel 10-kHz high-frequency (HF10 Therapy) is superior to 
traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg 
pain: The SENZA-RCT Randomized Controlled Trial. Anesthesiology 2015; 123:851-860. 
8. De Ridder D, Plazier M, Kamerling N, et al. Burst spinal cord stimulation for limb and back 
pain. World Neurosurgery 2013; 80:642-649. 
9. De Ridder D, Vanneste S, Plazier M, et al. Burst spinal cord stimulation: toward paresthesia-
free pain suppression. Neurosurgery 2010; 66:986-990. 
10. Wei XF, Grill WM. Impedance characteristics of deep brain stimulation electrodes in vitro and 
in vivo. J Neural Eng. 2009; 6:046008. 
 11. Sankar V, Patrick E, Dieme R, et al. Electrode impedance analysis of chronic tungsten 
microwire neural implants: understanding abiotic vs. biotic contributions. Front Neuroeng. 
2014; 7:13. 

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12. Reilly JP, Freeman VT, Larkin WD. Sensory effects of transient electrical stimulation--
evaluation with a neuroelectric model. IEEE Trans Biomed Eng. 1985; 32:1001-1011. 
13. Han X, Boyden ES. Multiple-color optical activation, silencing, and desynchronization of 
neural activity, with single-spike temporal resolution. PLoS One. 2007; 2:e299. 
14. Tilley DM, Cedeño DL, Kelley CA, Benyamin R, Vallejo R. Spinal cord stimulation modulates 
gene expression in the spinal cord of an animal model of peripheral nerve injury. Reg. Anesth. 
Pain Med. 2016. 41:750-756. 
15. Vallejo R, Tilley DM, Cedeño DL, Kelley CA, DeMaegd M, Benyamin R. Genomics of the Effect 
of Spinal Cord Stimulation on an Animal Model of Neuropathic Pain. Neuromodulation. 2016. 
6:576-586. 
16. Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 
2007; 10:1361-1368. 
17. von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal 
neural mechanisms. Neuron. 2012; 73:638-652. 
18. Agnesi F, Blaha CD, Lin J, et al. Local glutamate release in the rat ventral lateral thalamus 
evoked by high-frequency stimulation. J Neural Eng. 2010; 7:26009. 
19. Todd KJ, Darabid H, Robitaille R. Perisynaptic glia discriminate patterns of motor nerve activity 
and influence plasticity at the neuromuscular junction. J Neurosci. 2010; 30:11870-11882.  
20. Roitbak AI, Fanardjian VV. Depolarization of cortical glial cells in response to electrical 
stimulation of the cortical surface. Neuroscience. 1981; 6:2529-2537. 
21. Shealy CN, Mortimer JT, Reswick J. Electrical inhibition of pain by stimulation of the dorsal 
column: preliminary clinical reports. Anesth Anal 1967; 46:489-491. 
22. Deer TR, Mekhail N, Provenzano D, et al. The appropriate use of neurostimulation of the 
spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic 
diseases: the neuromodulation appropriateness consensus committee. Neuromodulation 
2014; 17:515-550. 
23.  North JM, Hong KJ, Cho PY. Clinical Outcomes of 1 kHz Subperception Spinal Cord Stimulation 
in Implanted Patients with Failed Paresthesia-Based Stimulation: Results of a Prospective 
Randomized Controlled Trial. Neuromodulation. 2016. [Epub ahead of print].  

Trialing of PM modulation therapy in patients with chronic intractable back pain with or without leg pain. 
 
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35 
24. Merrill DR, Bikson M, Jefferys JG. Electrical stimulation of excitable tissue: design of 
efficacious and safe protocols. J Neurosci Methods 2005; 141:171-198. 
25. Deer TR, Mekhail N, Provenzano D, et al. The appropriate use of neurostimulation: avoidance 
and treatment of complications of neurostimulation therapies for the treatment of chronic 
pain. Neuromodulation. 2014; 17:571-597. 
26. Manchikanti L, Abdi S, Atluri S, et al. An update of comprehensive evidence-based guidelines 
for interventional techniques in chronic spinal pain. Part II: guidance and recommendations. 
Pain Physician. 2013; 16:S49-S283. 
27. Cameron T. Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: a 
20-year literature review. J Neurosurg 2004; 100:254-267. 
28. Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for chronic back and leg pain and 
failed back surgery syndrome: a systematic review and analysis of prognostic factors. Spine 
(Phila Pa 1976) 2005; 30:152-160. 
29. Hou S, Kemp K, Grabois M. A Systematic Evaluation of Burst Spinal Cord Stimulation for 
Chronic Back and Limb Pain. Neuromodulation. 2016. 19:398-405. 

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10.  APPENDICES 
A. Informed Consent Process 
A1. Informed Consent Procedure 
A2. Informed Consent Form 
A3. Addendum to Informed Consent Document 
B. Case Report Forms: 
B1. CRF01: Inclusion and Exclusion Criteria  
B2. CRF02: Baseline General Health and Medications 
B3. CRF03: Information Section 
B4. CRF04: Baseline Pain Assessment 
B5. CRF05: Conventional SCS Pain Assessment 
B6. CRF06: Polymodal SCS Pain Assessment  
B7. CRF07: Stimulation Sensation Assessment  
B8. CRF08: Impression of Improvement and Patient Satisfaction 
B9. CRF09: Adverse Events 
B10. CRF10: Device Accountability and Polymodal SCS Therapy Settings 
C. Adverse Event Definition 
D. Device Related Information: 
D1. Investigational Device Label and Description 
D2. Patient Manual 
D3. Research System Characteristics Statement from Manufacturer 
E. Responsibilities of Investigators and Sponsors for Non-Significant Risk Device Studies 

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1  
The Global Pain Therapeutics Market Analysis, R&D Pipelines and Competitive Landscape, Arrowhead Publishers, 2007, pp. 408. 
2  
Institute of Medicine (US) Committee on Advancing Pain Research C, and Education. Relieving Pain in America: A Blueprint for Transforming 
Prevention, Care, Education, and Research. Washington (DC): National Academies Press (US), 2011, pp. 2.  
3  
Smits H, van Kleef M, Holsheimer J, et al. Experimental spinal cord stimulation and neuropathic pain: mechanism of action, technical aspects, 
and effectiveness. Pain Practice 2013; 13:154-168.   
4 
Melzack R, Wall Pain mechanisms: A new theory. Science 1965; 150:971-979. 
5  
Al-Kaisy A, Van Buyten JP, Smet I, et al. Sustained effectiveness of 10 kHz high-frequency spinal cord stimulation for patients with chronic, 
low backpain: 24-month results of a prospective multicenter study. Pain Medicine 2014; 15:347-354. 
6  
Van Buyten JP, Al-Kaisy A, Smet I, et al. High-frequency spinal cord stimulation for the treatment of chronic back pain patients: results of a 
prospective multicenter European clinical study. Neuromodulation 2013; 16:59-65. 
7  
Kapural L, Yu C, Doust MW, et al. Novel 10-kHz high-frequency (HF10 Therapy) is superior to traditional low-frequency spinal cord 
stimulation for the treatment of chronic back and leg pain: The SENZA-RCT Randomized Controlled Trial. Anesthesiology 2015; 123:851-
860. 
8  
De Ridder D, Plazier M, Kamerling N, et al. Burst spinal cord stimulation for limb and back pain. World Neurosurgery 2013; 80:642-649. 
9  
De Ridder D, Vanneste S, Plazier M, et al. Burst spinal cord stimulation: toward paresthesia-free pain suppression. Neurosurgery 2010; 
66:986-990. 
10  
Wei XF, Grill WM. Impedance characteristics of deep brain stimulation electrodes in vitro and in vivo. J Neural Eng. 2009; 6:046008. 
11  
Sankar V, Patrick E, Dieme R, et al. Electrode impedance analysis of chronic tungsten microwire neural implants: understanding abiotic vs. 
biotic contributions. Front Neuroeng. 2014; 7:13. 
12  
Reilly JP, Freeman VT, Larkin WD. Sensory effects of transient electrical stimulation--evaluation with a neuroelectric model. IEEE Trans 
Biomed Eng. 1985; 32:1001-1011. 
13  
Han X, Boyden ES. Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal 
resolution. PLoS One. 2007; 2:e299. 
14  
Tilley DM, Cedeño DL, Kelley CA, Benyamin R, Vallejo R. Spinal cord stimulation modulates gene expression in the spinal cord of an animal 
model of peripheral nerve injury. Reg. Anesth. Pain Med. 2016. Aug 9. [Epub ahead of print]. 
15  
Vallejo R, Tilley DM, Cedeño DL, Kelley CA, DeMaegd M, Benyamin R. Genomics of the Effect of Spinal Cord Stimulation on an Animal Model 
of Neuropathic Pain. Neuromodulation. 2016. 6:576-586. 
16  
Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007; 10:1361-1368. 
17  
von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron. 2012; 73:638-652. 
18  
Agnesi F, Blaha CD, Lin J, et al. Local glutamate release in the rat ventral lateral thalamus evoked by high-frequency stimulation. J Neural 
Eng. 2010; 7:26009. 
19  
Todd KJ, Darabid H, Robitaille R. Perisynaptic glia discriminate patterns of motor nerve activity and influence plasticity at the neuromuscular 
junction. J Neurosci. 2010; 30:11870-11882.  
20  
Roitbak AI, Fanardjian VV. Depolarization of cortical glial cells in response to electrical stimulation of the cortical surface. Neuroscience. 
1981; 6:2529-2537. 
21  
Shealy CN,Mortimer JT,Reswick J. Electrical inhibition of pain by stimulation of the dorsal column: preliminary clinical reports. Anesth Anal 
1967; 46:489-491. 
22  
Deer TR, Mekhail N, Provenzano D, et al. The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the 
treatment of chronic pain and ischemic diseases: the neuromodulation appropriateness consensus committee. Neuromodulation 2014; 
17:515-550. 
23  
North JM, Hong KJ, Cho PY. Clinical Outcomes of 1 kHz Subperception Spinal Cord Stimulation in Implanted Patients with Failed Paresthesia-
Based Stimulation: Results of a Prospective Randomized Controlled Trial. Neuromodulation. 2016. [Epub ahead of print].  
24  
Merrill DR, Bikson M, Jefferys JG. Electrical stimulation of excitable tissue: design of efficacious and safe protocols. J Neurosci Methods 
2005; 141:171-198. 
25  
Deer TR, Mekhail N, Provenzano D, et al. The appropriate use of neurostimulation: avoidance and treatment of complications of 
neurostimulation therapies for the treatment of chronic pain. Neuromodulation. 2014; 17:571-597. 
26  
Manchikanti L, Abdi S, Atluri S, et al. An update of comprehensive evidence-based guidelines for interventional techniques in chronic spinal 
pain. Part II: guidance and recommendations. Pain Physician. 2013; 16:S49-S283. 
27  
Cameron T. Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: a 20-year literature review. J Neurosurg 2004; 
100:254-267. 
28  
Taylor RS, Van Buyten JP, Buchser E. Spinal cord stimulation for chronic back and leg pain and failed back surgery syndrome: a systematic 
review and analysis of prognostic factors. Spine (Phila Pa 1976) 2005; 30:152-160. 
29  
Hou S, Kemp K, Grabois M. A Systematic Evaluation of Burst Spinal Cord Stimulation for Chronic Back and Limb Pain. Neuromodulation. 
2016. 19:398-405.