Spinal Cord Stimulation for Restoration of Function in Lower-Limb Amputees, 90-Day
Phase: NA
Conditions: Traumatic Amputation of Lower Extremity, Phantom Limb Pain
Sponsor: Lee Fisher, PhD

 
 
SPINAL CORD STIMULATION 
FOR RESTORATION OF 
FUNCTION IN LOWER-LIMB 
AMPUTEES 
90-Day 
Lee Fisher, PhD 
 
Abstract 
The goals of this study are to provide sensory information to lower limb 
amputees and reduce their phantom limb pain via electrical stimulation of 
the lumbar spinal cord and spinal nerves using FDA-cleared spinal cord 
stimulator leads for up to 90 days. 
 
 
10/15/2025 

 

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INVESTIGATIONAL DEVICE EXEMPTION (IDE) APPLICATION 
 
SECTION D: TABLE OF CONTENTS 
 
D Investigational Plan .........................................................................................................2 
1.0 Purpose of the Investigation.....................................................................................2 
1.1 
Name of investigational device ......................................................................2 
1.2 
Intended use of the investigational device .....................................................2 
1.3 
Objectives of the clinical investigation ..........................................................2 
1.4 
Anticipated duration of the clinical investigation ..........................................4 
2.0 Clinical protocol .......................................................................................................4 
2.1 
Title of clinical protocol .................................................................................4 
2.2 
Study design ...................................................................................................4 
2.3 
Subject selection .............................................................................................5 
2.4 
Study procedures ............................................................................................7 
2.5 
Study outcome evaluations ...........................................................................19 
3.0 Risk Analysis .........................................................................................................22 
3.1 
Anticipated risks ...........................................................................................22 
3.2 
Summary of risks and justification related to the use of spinal cord 
stimulation ....................................................................................................33 
4.0 Description of the Device ......................................................................................33 
4.1 
Belt-worn stimulator and data acquisition system .......................................33 
4.2 
Spinal cord stimulator leads .........................................................................33 
4.3 
University of Pittsburgh Education & Compliance Office – Human Subject 
Research .......................................................................................................34 
4.4 
Data Safety Monitoring Board .....................................................................34 
4.5 
Monitoring by study team ............................................................................35 
5.0 Labeling .................................................................................................................35 
6.0 Consent Materials ..................................................................................................36 
7.0 IRB Information .....................................................................................................36 
8.0 Additional Records and Reports ............................................................................36 
8.1 
Data handling and record-keeping ...............................................................36 
8.2 
Record maintenance and retention ...............................................................37 
SECTION D References .......................................................................................................39 
 
 

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D 
Investigational Plan 
1.0 Purpose of the Investigation 
1.1 Name of investigational device 
SCS for Lower-Limb Amputations (SCS-LLA) 
1.2 Intended use of the investigational device 
In the proposed study, we will investigate the efficacy of community use and safety of a 
neuroprosthetic system that uses spinal cord stimulation to restore sensory feedback after lower-
limb amputation. The device will consist of an external data acquisition and stimulation system 
(Nomad Research System, Ripple LLC, Salt Lake City, UT) connected to 1-3 percutaneously 
inserted spinal cord stimulation (SCS) leads which have prior premarket clearance and approval 
(Abbott Medical Spinal Cord Stimulation (SCS) System, 510(k) K960728 and PMA P010032), 
see the attached Right of Reference letter, Appendix A) and a set of sensors mounted on the 
subject’s prosthesis and limbs. Ongoing experiments in our lab have focused on the use of SCS 
to evoke sensations in the missing foot and shank after trans-tibial amputation. In those 
experiments, we used similar SCS leads to those that will be used in this study, percutaneously 
placed in the lateral lumbosacral epidural space for up to 29 days. All experiments to date have 
been deemed “Non-Significant Risk” by the University of Pittsburgh Institutional Review Board 
and performed under their approval. During those experiments, the external connector from the 
percutaneous leads is attached to an external stimulator during in-lab testing in our facilities at 
the University of Pittsburgh. Currently no stimulation is performed outside of the lab or clinic 
environment. During the proposed study, we will perform similar experiments over an extended 
90-day period, and will also provide subjects with a portable stimulation and data acquisition 
system that can be used outside the lab environment for up to two weeks. During this two-week 
portion of the 90-day trial, subjects will transition from supervised use of the system to 
unsupervised use in the home and community. While ongoing lab-based experiments have been 
informative for our understanding of the ability to evoke and control the perception of sensations 
in the missing limb, ultimately, the goal of development of a somatosensory neuroprosthesis is 
for the system to be used in the community. Such community use will provide us with insight 
into the effects of daily and extended use of the system on function (e.g. balance control and gait 
stability) and changes in phantom limb pain. The extended duration of the experiments will also 
allow us to collect substantially more data and to prepare for the week-long trial of community 
use than can currently be achieved during the 29-day testing period.  
1.3 Objectives of the clinical investigation 
The proposed clinical investigation is a feasibility study directed toward the following aims: 
Specific Aim 1: Demonstrate the safety of the SCS-LLA system over a period of up to 90 days. 
We will monitor adverse events throughout the study, and these results will provide supporting 
data for future studies with larger cohorts and a fully implanted SCS system. 
Specific Aim 2: Characterize the sensations evoked by lumbar epidural spinal root stimulation in 
lower-limb amputees. 

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• Specific Aim 2a: Quantify the threshold (minimum charge and pulse rate) stimulus required 
to evoke sensory percepts and neurophysiological responses (e.g. reflexive EMG responses,) 
during SCS, and monitor changes in those percepts and responses over time. These results 
will provide insight into the design requirements for a future SCS system, as well as a point 
of comparison among subjects and with other studies in the scientific literature. Additionally, 
the stability of the responses will provide insight into the feasibility of long-term use of the 
device. 
• Specific Aim 2b: Evaluate the relationship between stimulation parameters (e.g. pulse width, 
pulse amplitude, stimulus location, etc.) and the modality and naturalness of perceived 
sensations. Lumbar SCS can evoke paresthesia referred to the amputated limb, but our goal is 
to produce meaningful (non-paresthetic) sensations. As we expect the stimulation parameters 
to have significant effects on the evoked sensations, we will perform standardized 
psychophysical examinations to determine the relationship between stimulation parameters 
and perceived sensations. These tests will be repeated at multiple points throughout the study 
to observe any changes that occur over multiple days of use. 
• Specific Aim 2c: Document the subjective perception of lower-limb amputees of lumbar SCS 
for restoration of sensation. To achieve widespread adoption of a sensory neuroprosthesis, it 
will be crucial for amputees to perceive significant value from the device. As such, we will 
ask each subject to provide subjective feedback on their perceived utility of the sensory 
feedback provided by the device. 
Specific Aim 3: Characterize the effects of lumbar SCS on phantom limb sensations and 
phantom limb pain in lower-limb amputees. This aim is secondary to the primary study goals in 
Aims 1 and 2, and as such, we will not exclude individuals that do not experience phantom limb 
pain.  
• Specific Aim 3a: Document changes in phantom limb sensation during and shortly after 
lumbar SCS in amputees. Before placement of the spinal cord stimulator leads, we will 
document the subject's description of their perceived phantom limb. We will ask them to 
update their perception of the limb periodically throughout each experimental session, as 
well as within a month after the device has been removed. 
• Specific Aim 3b: Document changes in phantom limb pain during and shortly after lumbar 
SCS in amputees. Before placement of the SCS leads, we will ask subjects about their history 
of perceived phantom limb pain. We will ask them to update their pain level periodically 
throughout each experimental session, as well as within a month after the device has been 
removed. 
Specific Aim 4: Characterize the patterns of reflexive muscle activity that are evoked by SCS. 
Reflexive muscle activity plays a crucial role in maintaining standing balance and transitioning 
between phases of the gait cycle. As such, restoration of sensation may play an important role in 
restoring these functions. Importantly, these reflexes are context-dependent, and may change 
with posture. 
Specific Aim 5: Characterize changes in control of a prosthetic limb in the presence of sensory 
feedback. The long-term goal of this line of research is to provide sensory feedback that can be 
used in the control of a prosthesis. In this study, we will test the subject's ability to stand and 
walk with and without sensory feedback provided by SCS. Using either a virtual prosthetic limb 
or an instrumented prosthesis, SCS will be modulated based on signals recorded from the limb 

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such as pressure under the foot or joint angles. In both the presence and absence of stimulation, 
subjects will be asked to perform tasks such as standing quietly and walking. We will perform a 
battery of clinically validated balance and gait metrics to evaluate the effects of sensory feedback 
on control of the prosthesis. 
Specific Aim 6: Explore how sensations, balance, gait, and pain change after subjects have used 
the system in the community for up to two weeks. While lab-based studies will provide insight 
into the types of sensations and reflexive responses that can be evoked by SCS, as well as the 
impact of those sensations on balance control and gait stability, subjects’ exposure to the device 
will be limited to tens of hours over the duration of the study. This limited access will restrict 
subjects’ ability to learn to use the device and to incorporate sensory feedback into activities of 
daily living. Additionally, the effects on PLP may require an extended presentation of 
stimulation. We will perform detailed evaluations of the effects of sensory restoration in these 
subjects, monitor any changes in PLP and evoked reflexive activity, and track the extent of their 
use of the device during up to two weeks of community use, including up to one week of 
unsupervised use. 
1.4 Anticipated duration of the clinical investigation 
Active participation will last no more than the 90 days after the leads are placed. However, as 
several pre-surgical and post-removal procedures are required (e.g. balance and gait testing, pain 
questionnaires, blood work, MRSA screening, EKG, MRI), total duration of the subject's 
participation in this study across all visits (including screening, experimental testing, and follow-
up surveillance) may last up to 9 months. 
2.0 Clinical protocol 
2.1 Title of clinical protocol  
“Spinal Cord Stimulation for Restoration of Function in Lower-Limb Amputees” 
2.1.1 Protocol number 
University of Pittsburgh, STUDY19010019 
2.1.2 Version number and date 
Modification Version: STUDY19010019 
Approval Date: 8/2/2022 
IRB Expiration Date: 8/1/2023 
2.2 Study design 
2.2.1 General study design 
This study is a prospective, non-randomized, open-label, descriptive, interventional study.  
2.2.2 Study design schematic 
Figure 1 illustrates the proposed study design. Procedures are discussed in Section 2.4. 

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2.3 Subject selection 
2.3.1 General characteristics of the proposed subject population 
The subjects for this study will be individuals between the ages of 22-70 with an 
amputation of one lower limb at a level between the ankle and knee joints. Subjects should 
be at least 6-month post-amputation at the time of study participation. To ensure their 
safety during participation, subjects will be screened to ensure that they have no serious 
diseases or disorders that could be complicated by participation. Due to the greater than 
minimal risk designation of the study, we will be using adult subjects to ensure that 
participants are mature enough to understand the tasks, as well as the risks, involved; 
further, we want to ensure that the central nervous system is fully developed prior to 
enrollment in this study.  
2.3.2 Anticipated number of research subjects 
Up to 15 total subjects may undergo research procedures, with the goal of completing all 
experiments with 10 subjects. Recruitment rates will be monitored by our DSMB. Because 
it is possible that a subject may enroll and then be determined to be ineligible, the 
 
Figure 1. Study design schematic 

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maximum number of subjects enrolled may exceed the number who undergo device 
placement. Subjects will be enrolled as necessary to maintain the target number of 
subjects. Recruitment will not begin until we have received all approvals.  
2.3.3 Inclusion criteria 
1) Subjects must have an amputation of one lower limb, at a level between the ankle and 
knee joints. Minor amputation of the contralateral limb (i.e. toes or partial foot) is not 
exclusionary. 
2) Subjects must be over 6-month post-amputation at the time of lead placement. 
3) Subjects must be between the ages of 22 and 70 years old. Participants outside this age 
range may be at an increased medical risk and have an increased risk of fatigue during 
testing. 
4) Subjects must have used their current prosthesis for at least 6 months and achieved at 
least K-1 ambulator status at the time of lead placement, as determined by the Amputee 
Mobility Predictor. 
2.3.4 Exclusion criteria 
1) Subjects must not have any serious disease or disorder that could affect their ability to 
participate in this study. 
2) Female subjects of childbearing age must not be pregnant or breast-feeding. 
3) Subjects must not be receiving medications that affect blood coagulation. 
4) Subjects must not have an allergy to contrast medium or renal failure that could be 
exacerbated by the contrast agent used in MRIs. For this study, renal insufficiency will 
be determined through blood work and defined as BUN of 30 mg/dl or more and 
Creatinine of 1.5 mg/dl or more. 
5) Subjects may not have a hemoglobin A1c level above 8.0 mg/dl at time of implant. 
6) Subjects may not have any implanted medical devices that are not cleared for MRI. 
7) Subjects with a T-Score higher than 63 on the 18-question Brief Symptoms Inventory 
(BSI-18) who have undergone discussions with and been deemed unsuitable by the 
Principal Investigator, a study physician, and a psychologist 
8) Subjects may not have a cardiac pacemaker. 
9) Subjects may not have a cardioverter defibrillator. 
10) Subjects may not be currently receiving diathermy therapy. 
11) Subjects may not have an implanted infusion pump. 
12) Subjects may not be immunosuppressed or currently receiving immunosuppressive 
medications. 
13) Subjects may not have a profession (e.g. radiology technologist) or medical condition 
(e.g. remissory cancer involved regular follow-up x-rays) that would increase radiation 
exposure in the 12 months prior to starting or after ending participation in the study.  

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2.4 Study procedures 
2.4.1 
Screening procedures 
We will recruit subjects from two University of Pittsburgh Institutional Review Board 
(IRB) approved registries developed by the Human Engineering Research Laboratories 
(Pitt IRB# PRO12080311) and the Department of Physical Medicine and Rehabilitation 
(Pitt IRB# PRO12030122). All members of the registry have agreed to participate in the 
registry, and have given permission to be contacted for future research. The IRB approved 
flyer for this study will be distributed to potential subjects according to the procedures 
established in the registry IRB approved protocols. The recruitment flyer will be 
accompanied by a letter from the registry PI/coordinator stating why they are receiving 
information about our study. In response to the recruitment flyer, potential subjects can 
directly contact the research team if interested in participating. We may also post the 
recruitment flyer, or other approved recruitment materials, on websites affiliated with our 
laboratory, the Physical Medicine & Rehabilitation Department, and the University of 
Pittsburgh. We may also recruit through organizations representing our subject population 
groups, such as assistive technology suppliers, adaptive sports organizations, amputee 
support groups, and amputation or other related clinics. The recruitment materials can also 
be made available in places such as hospitals, clinics or related events or promoted in 
social media or websites targeted towards individuals with amputation. Clinicians in the 
Department of Physical Medicine and Rehabilitation, Center for Assistive Technology, 
UPMC Centers for Rehab Services, and other departments at UPMC Presbyterian and 
UPMC Mercy who are knowledgeable about our study may distribute recruitment 
materials to their patients if they think they may be eligible. Clinicians or their 
administrative designees may also query their patient databases to find potentially eligible 
participants and contact these individuals directly. Individuals may contact our study team 
directly in response to the clinicaltrials.gov website, scientific publications, media, or other 
means besides our planned recruitment methods. 
If an individual contacts us and is interested in this research study, we will provide that 
individual with information about the study (brochure, recruitment letter and/or consent 
form). We may conduct a phone screening to assess some of the inclusion and exclusion 
criteria. The initial screening can be conducted over the phone, in person, or using face-to-
face video conference software, such as Skype or Facetime, for the individual’s 
convenience. The purpose of this screening is to potentially eliminate the burden of travel 
on a potential participant who may not be eligible for the study. If any of the phone script 
screening questions indicate exclusion of that individual, the screening questions will stop 
at that point and the individual will be kindly told that they are not eligible for the study. If 
none of the phone script questions indicate exclusion from the study, then the individual 
will be asked to meet with the research team to further discuss study participation.  
We will also use the Brief Symptom Inventory 18 (BSI-18) to screen all potential 
participants. Given the known increased prevalence of anxiety and depressed mood in 
individuals with amputation and chronic pain, it is our intent to use the BSI-18 to screen 
for mood symptoms as part of the consent process. The presence of symptoms, as reported 
on the BSI-18, will not exclude individuals from participating in the study – rather, 
responses given during the BSI-18 survey will be used as a tool to guide discussion 

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between the Principal Investigator, a study physician, and the potential subject. If an 
individual expresses severe depressed or anxious mood, resources will be provided to 
assist the individual in seeking appropriate mental health treatment. For those individuals 
with a BSI-18 T-score above 63, a meeting with a psychologist will be scheduled to assess 
their suitability for the study. Due to the sensitive nature of the questions on the BSI-18 
survey, we will request that subjects complete the BSI-18 in person at the first screening 
visit, where appropriate clinical help, including a clinical psychologist, will be available. 
Once a potential subject has been identified, the subject will be educated about the study, 
study goals, study tasks, and study requirements. Initial questions will be answered and 
they will be provided with a copy of the consent form. Initial contact may be made by any 
investigator, but as this study requires a surgical procedure with the inherent risks of 
surgery, study physicians will be available to discuss any participant questions, either in-
person or via teleconferencing software, such as Skype or Facetime, prior to consent. The 
potential participant will also be encouraged to discuss this study and the information 
provided in the consent form with her or his treating physician. After the subject has met 
with the study team, and agreed to participate in the study, they will be consented by a 
physician-investigator. If the individual is capable, they will sign the consent form.  
Once written informed consent is obtained, the subject is enrolled in the study and is 
assigned a unique subject ID. A physician-investigator will verify the eligibility of the 
subject by assessing most of the eligibility criteria after consent via self-report. This will be 
documented on an "Eligibility Checklist" form. 
After informed consent and after the participant's verbal self-report of eligibility criteria, an 
in-person clinical evaluation will be performed. Additionally, medical records will be 
accessed if additional information is required to perform pre-operative planning and review 
pertinent medical history, allergies, medications and radiology images. 
2.4.1.1 MRI screening 
Prior to undergoing an MRI for this study, a person will be asked about any implanted 
metal in their body. The screening covers items that would possibly exclude a participant 
from the study. In some cases, an x-ray may be requested by radiology prior to MRI to 
verify the shape and location of an implanted device. Female participants of childbearing 
potential will be screened for pregnancy prior to MRI using a urine pregnancy test. The 
completed MRI screens will be kept in a locked file cabinet located in a locked office to 
assure subject confidentiality. 
2.4.2 
Experimental procedures 
Pre-surgical procedures and device placement will occur within 6 months after the subject 
undergoes screening procedures. We will work with each individual to determine the 
optimal testing schedule. The schedule will be designed to meet study goals and complete 
specific study tasks which will change over the duration of the study. The participant's 
engagement and training preferences will also be considered in this process. We will 
photograph or videotape portions of the experimental session. Appropriate permission will 
be obtained as needed for any photographs or videotaping of participants. Female 
participants will be encouraged to avoid getting pregnant throughout the duration of the 
research study. Experimental procedures are described below. 

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2.4.2.1 Demographic and medical history questionnaire 
The subject will be asked to provide basic demographic information (age, weight, height, 
etc.) via self-report. We will also ask questions about their medical history including the 
date of amputation and their current level of function, prosthetic usage, as well as recent 
history and current status of phantom limb sensations and pain. We will also ask questions 
related to improvement of quality of life and neuroprosthetic technology.  
2.4.2.2 Pre-operative physical and screening 
Prior to the lead placement procedure, participants will undergo several screening 
procedures, including x-rays and clinical lab workups. For diabetic participants with 
elevated hemoglobin A1c levels (greater than 8.0 mg/dl), we may perform repeated blood 
draws within the 6 months following consent to ensure implant does not pose a risk of 
infection. If the participant’s levels remain consistently above 8.0 mg/dl within the 6-
month period following consent, we will not schedule lead placement, and will withdraw 
the participant from the study. 
 
If the subject does not have an elevated A1c level, within two weeks prior to the lead 
placement procedure, we will perform: pre-operative chest x-ray; a routine urinalysis with 
microscopy; a complete blood count with differential and platelets; a prothrombin time and 
international normalized ratio; an activated partial thromboplastin time; iron, prealbumin, 
albumin, and hemoglobin A1c levels; a vitamin D 25-OH screen for deficiency/toxicity; 
urine pregnancy screen; and a MRSA screen. If study physicians suspect the subject may 
have renal insufficiency, which would prevent the use of gadolinium-based contrast agents, 
we may also perform blood urea nitrogen (BUN) and creatinine (Cr) testing. In the case of 
inconclusive test results and at the discretion of the study physicians, we may need to ask a 
participant for repeated sample collection. All lab work and repeated testing will be 
performed through UPMC.  
2.4.2.3 Pre-operative structural MRI with contrast 
We will perform a pre-operative MRI of the spine with contrast, to image the region where 
we will be placing the stimulator leads. If MR images of the region of interest already exist 
in the subject's medical record, these may be used instead. The MRI can be performed at 
any UPMC facility or at the Magnetic Resonance Research Center at UPMC Presbyterian. 
2.4.2.4 Pre-operative or post-explant high resolution structural MRI without contrast 
If scheduling permits, we will perform a second pre-operative or post-explant MRI of the 
spine without contrast to generate a high resolution scan of the spinal cord and spinal roots. 
This scan will be co-registered with a post-operative high-resolution CT scan of the spine 
(see Section 2.4.2.13) so that we can accurately visualize the location of the leads with 
respect to neural tissue. These MRI scans are not critical to our primary scientific 
questions, but will potentially provide interesting additional data for understanding the 
relationship between electrode location and the sensations evoked by spinal cord 
stimulation. Additionally, scheduling MRI scans can be highly challenging for studies with 
small sample sizes that do not have dedicated time slots. As such, we will attempt to 
schedule an MRI in the pre-operative or post-explant time windows, but may not collect 

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these scans if scheduling is impossible. High resolution structural MRI will be performed 
at the Magnetic Resonance Research Center at UPMC Presbyterian. 
2.4.2.5 Pre-operative somatosensory function testing 
Participants in this study may have impaired sensory function in the contralateral, intact 
limb. To account for those deficits when measuring functional control of the prosthesis 
(e.g. balance control), we may perform pre-operative measurements to quantify sensory 
function in the intact and residual limb. A variety of sensory function tests may be 
performed, such as tactile sensitivity testing, with Von Frey filaments or a mechanized 
tactor system, kinesthetic sensitivity testing, via manual or mechanized range of motion 
testing at the ankles and toes, and reaction time testing, in which a mechanical or electrical 
stimulus is applied to the limb and the subject must respond as quickly as possible (such as 
by clicking on a screen or pushing a button) to indicate detection of the stimulus. To reduce 
the burden on participants, we will not repeat testing on participants who are enrolled in 
another study where somatosensory data has already been collected. Additionally, 
transcutaneous stimulation pulses will be bi-phasic and charge balanced with frequency ≤ 1 
kHz, pulse duration ≤ 1 ms, and amplitude ≤ 100 mA. We will start stimulation at a low 
amplitude (e.g. 1 mA) and slowly increase amplitude to avoid inducing pain. If we identify 
stimulation parameters that are painful, we will cease stimulation above that amplitude. 
The transcutaneous electrical stimulation will be delivered intermittently for the duration 
of testing, in a pattern of 5-10 seconds ‘ON’ for the pulses, followed by 30-50 seconds 
‘OFF’. 
2.4.2.6 Pre-operative 12-lead EKG 
Up to 12 removable electrodes will be placed on the subject's chest and/or limbs. EKG 
wires will be attached to a monitor and the subject will be instructed to breathe normally 
during monitoring. 
2.4.2.7 Decolonization for Surgical Site Infection Prevention 
Participants will be instructed to shower each day for 5 days prior to surgery and the 
morning of surgery. An ointment will be provided to be used around the nose. These will 
help prevent bacteria on the body from causing an infection at the implant site. 
Decolonization will be performed before implantation and lead removal (as long as the 
removal procedure is not emergent). Also, we will provide participants with verbal and 
written instructions to care for their incision.  
 
2.4.2.8 Prophylactic antibiotics 
We will follow the standard clinical procedures to minimize the risks associated with 
percutaneous placement of electrodes. Prophylactic antibiotics will be administered 
intravenously 30 minutes before surgery and may be maintained as directed by a study 
physician and their clinical team. We will generally use cefazolin for this procedure; 
however, if the subject tests positive for or has a charted history of MRSA, intravenous 
vancomycin will also be administered. If the subject has a severe penicillin allergy, 
vancomycin will be administered without cefazolin. We have excluded pregnant females 
and those with renal failure (see Section 2.3.4) as they may be at an increased risk for 
complications resulting from administration of the antibiotics. Sterile silver dressings will 

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be applied to the insertion site, covering the protruding leads, to minimize the risk of 
infection. These procedures will greatly minimize the risk of infection and may vary based 
on the study physicians’ clinical judgment and input from Infectious Disease experts.  
2.4.2.9 Pre-operative sedation 
The subject will see an anesthesiologist for procedural sedation to be used primarily during 
lead anchoring procedures. Small doses of Fentanyl and Versed may be administered 
intravenously. General anesthesia may also be used upon subject’s request and 
anesthesiologist approval. Sedative administration may vary based on the anesthesiologist's 
clinical judgment. 
2.4.2.10 Fluoroscopically guided lead placement procedure 
Between one and three leads will be placed in the lumbosacral epidural space near the 
spinal cord. Clinical practice commonly includes placement of two or three of these leads 
in the epidural space. Leads will be placed by a physician with experience in spinal cord 
stimulation, at UPMC Mercy or UPMC Presbyterian using the following procedures, 
although, based on their professional judgment, they may make slight modifications to 
improve targeting and outcomes. The subject will be taken to a fluoroscopy suite or 
operating room, placed in a prone position with a pillow under the abdomen to decrease 
the normal lumbar lordosis. Each staff member involved in the procedure will sterilely 
scrub in with sterile gowns and gloves. The skin overlying the thoracolumbar area will be 
prepped and draped in aseptic fashion with Hibiclens and betadine. For local anesthesia, 
1% lidocaine on a 22-gauge 3.5-inch spinal needle will be used in the skin and 
subcutaneous tissue. For each of the leads, a 14-gauge epidural Tuohy needle will be 
advanced through the L1-L2 space or a nearby intervertebral space to the posterior epidural 
space via loss-of-resistance technique. Needle location will be confirmed in anteroposterior 
(AP), lateral, and contralateral oblique fluoroscopy views. An 8-contact stimulator lead, 
which is designed to span 2-3 spinal segments, will then be advanced into the L3-S1 
posterior epidural space and steered laterally using the accompanying catheter under live 
fluoroscopic guidance in the AP, lateral, and contralateral oblique fluoroscopy views. The 
lead may be connected to an additional extension lead that is included in the approved 
epidural stimulation system (under PMA P010032). The external portion of the lead will be 
connected to one of two external stimulators: 1) an Abbott External Pulse Generator 
included in PMA P010032 and 510(k) K960728, or 2) a current-controlled 32-channel 
neural stimulator (manufactured by Ripple, LLC, see Section E for more detail), a device 
which, according to the manufacturer "...meets safety standards for human research studies 
through IRB approval for both recording and stimulation.” During a brief volley of 
stimulation, the subject will be asked to report the region of their body over which they 
feel any evoked sensations. The lead placement will be iteratively adjusted based on 
subject feedback until the evoked sensations are referred appropriately to the amputated 
limb. 
2.4.2.11 Lead anchoring procedure 
Once all of the percutaneous leads have been placed under fluoroscopic guidance, a 
neurosurgeon and study physician with extensive experience in spinal cord stimulation will 
secure the leads to the thoracolumbar fascia. Each 14-gauge epidural Tuohy needle will be 
kept in place until the removal at the end. We will apply a generous amount of 1% 

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preservative-free local anesthetic in the skin and subcutaneous tissues. The neurosurgeon 
will make a small incision with a scalpel at approximately 1 inch cranial and 1 inch caudal 
to each needle. The neurosurgeon will bluntly dissect around the approximate 2-inch 
opening with surgical tools in the subcutaneous tissue. The neurosurgeon will cauterize any 
subcutaneous bleeding vessels using monopolar and/or bipolar cautery devices. The 
dissection will then extend anteriorly to the thoracolumbar fascia. Once the thoracolumbar 
fascia is identified, the study physician will remove the epidural Tuohy needle under live 
fluoroscopic guidance to make sure there is no movement of the percutaneous lead at each 
level. Then an anchoring device will be deployed on top of the percutaneous lead and 
advanced to the most posterior aspect of the thoracolumbar fascia. The neurosurgeon 
and/or a neurosurgery resident will use the appropriate suture technique to secure the 
anchoring device in the thoracolumbar fascia at each level. We will use fluoroscopic 
imaging to make sure there is no lead migration during this process. Once each of the 
percutaneous leads have been secured in the thoracolumbar fascia, we will tunnel each of 
the percutaneous leads from the subcutaneous tissue out through the skin at a separate exit 
site. We may then utilize vancomycin powder and iodine solution at the needle entry site. 
The neurosurgeon and/or a neurosurgery resident will use suturing technique to close the 
subcutaneous tissues and skin. We will apply a sterile dressing to both the needle entry 
sites and the skin exit sites. The patient will be taken to a monitored bed in post-op for 
recovery. The entire procedure, including lead placement and anchoring, is expected to 
take approximately three to four hours. 
Immediately following lead placement and up to 5 times per week for the following 90 
days, experimental procedures will be performed. The day-to-day experimental procedures 
for each session will ultimately be decided by the PI, as they may depend on a variety of 
factors including progress towards our experimental goals, the current state of our 
technical setup (e.g. if hardware breaks and must be repaired), and the number of hours the 
subject is available on a given day. A typical day of testing might include psychophysical 
examination of sensations (e.g. receptive field mapping, measurement of threshold and 
just-noticeable difference) in the morning, followed by a lunch break, followed by x-rays 
and testing of the control of the prosthesis with sensory stimulation in the afternoon. Each 
testing session will be limited to no more than 8 hours, and will include breaks. Meals will 
also be provided. During experiments, SCS stimulation will either be delivered by an 
Abbott external stimulator or a current-controlled 32-channel neural stimulator 
(manufactured by Ripple, LLC; refer to Section E of this application for more detail). 
2.4.2.12 Post-operative pain medication 
If a subject is experiencing pain due to lead placement or removal, the study physician may 
choose to prescribe pain relief medication, such as Norco 5-325. Number of tablets 
prescribed will be at physician discretion. 
2.4.2.13 Post-operative high resolution CT to document lead location 
After lead placement, we will perform a high-resolution CT scan of the spine to document 
the 3-dimensional location of the leads with respect to bony landmarks. This scan will be 
co-registered with the pre-operative or post-explant high resolution MRI, if performed, to 
determine the location of the leads with respect to the spinal cord and spinal roots. This 
scan can be performed at any UPMC facility. 

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2.4.2.14  Weekly x-ray to document lead migration 
Once per week for the first four weeks’ post-implant and once every two weeks for the 
remainder of the 90 days, multi-view x-rays (including AP and lateral views) of the 
thoracic and/or lumbosacral spine will be taken to document the location of the leads and 
any movement that may have occurred. We will attempt to correlate movement of the 
electrodes with any documented changes in stimulation thresholds or the types of sensory 
percepts that are evoked by stimulation. 
2.4.2.15 Weekly clinical exams and infection monitoring 
Subjects will have clinical exams, in-person or via telemedicine visits, at least weekly 
following lead placement to monitor signs of infection. Physicians will verify that subjects 
do not have a fever, new redness at the incision site, or other signs indicative of infection. 
The physician will also ask if there have been any changes in medications. If local 
infection is suspected during a weekly exam, the examining physician will request drawn 
blood work (complete metabolic panel, C-reactive protein, erythrocyte sedimentation rate, 
complete blood count), swab the incision sites for culture, and schedule an additional 
clinical exam within 24 hours. A course of 5 to 7 day oral antibiotics will also be 
administered if superficial infection is suspected. Any signs of systemic infection 
(leukocytosis greater than 12x109/L, fever, or positive blood cultures) or the presence of 
local infection with discharge suspicious for infection will result in immediate removal of 
leads at the infected site and administration of intravenous antibiotics recommended by 
Infectious Disease clinicians. Any local infections that do not show improvement with a 
course of antibiotics within 3 days will also result in lead removal. Infectious Disease will 
be consulted at all signs of infection and study physicians will follow all Infectious Disease 
directives. 
2.4.2.16 Psychological evaluation 
 
The subject will have opportunities to talk to a psychologist throughout the study, either 
over the phone, via telemedicine visits, or in person. These discussions can be scheduled 
regularly (at or shortly after the first screening visit and at approximately 1.5 months after 
implant) to discuss any concerns the subject may have. During each visit, the psychologist 
will assess the participant’s mood, discuss the subject’s expectations for the study, look for 
signs of discontent or frustration and discuss plans for after explant. The psychologist will 
provide written documentation of the assessments. By engaging in regular discussions, the 
psychologist will build a relationship with the participant that will help identify any 
changes in attitude or psychological status. The psychologist will also prepare the 
participant for life after the study. One follow-up visit will be scheduled approximately 3 
weeks after explant. In addition, the principal investigator and physician co-investigators 
will be interacting with the subject on a regular basis and can refer the subject to a 
psychologist at their discretion. If the subject has severe problems or concerns, he or she 
may be withdrawn from the study. 
 
2.4.2.17 Psychophysical testing 
We will conduct a series of psychophysical tests to establish the relationship between SCS 
and sensory perception. During psychophysical stimulation trials, an external stimulator 

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will be connected to the SCS lead, a volley of stimulation will be performed, and the 
subject will be asked to respond to a set of standard psychophysical questions, as well as to 
provide any additional comments. Stimulus parameters to vary include the following: 
Pulse amplitude, pulse width, and pulse frequency limits are on Abbott Medical's PMA 
P010032 and/or a charge injection of 30 µC/cm2, which is well below the generally 
accepted safe limit for stimulation through platinum/iridium macro-electrodes1. The values 
below were calculated for the surface area of an Abbott SCS electrode contact, which is a 
cylinder with 1.4 mm diameter and 3 mm length. 
• Pulse amplitude (7.9 mA output maximum per electrode contact) 
• Pulse width (maximum of 500 µs) 
• Pulse frequency (maximum of 1,200 Hz) 
• Spatial effects: groups of electrodes will be stimulated simultaneously to investigate the 
effects of spatial summation 
• Temporal effects: the pattern of stimulus pulses will be varied to model naturally 
occurring neural patterns (e.g. rapidly adapting or slowly adapting neurons) or engineering 
patterns (e.g. sinusoidal modulation) 
In clinical practice, the Abbott system is typically used for extended times throughout the 
day. As such, we do not expect that we will need to impose any upper limits on the total 
duration of stimulation applied throughout any experimental session or the entire study.  
Participants will be asked to identify where on their body any consciously perceived 
sensations were referred to, and will be asked to rate and describe various perceptual 
qualities of stimulation, such as naturalness, location, painfulness, and modality of 
sensation. 
Participants will also be asked to compare two or more successive stimulus trains and 
describe or compare the effects of stimulation. Examples of the kinds of comparisons that 
participants may be asked to make include: 
• Was the frequency of stimulus 1 higher or lower than stimulus 2? 
• Did stimulus 2 feel stronger or weaker than stimulus 1? 
• Which of stimuli 1, 2, or 3 felt like it came from the heel of the foot? 
2.4.2.18 Mechanical and/or electrical stimulation 
In order to provide a comparison between electrical stimulation and natural sensations, we 
will impart mechanical or electrical stimulation to either the residual limb or the 
contralateral limb, and ask subjects to document the perceived sensations. 
Examples of stimulation include: 
• Vibration of the skin using a mechanical tactor 
• Skin indentation using von Frey hairs 
• Passive movement of the limb 
• Transcutaneous electrical stimulation of peripheral nerve or skin using adhesive gel 
electrodes 

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• Imagined or observed somatosensory stimulation 
Responses from participants about sensations they may consciously experience during 
these peripheral stimuli will be recorded. Transcutaneous stimulation pulses will be bi-
phasic and charge balanced with frequency ≤ 1 kHz, pulse duration ≤ 1 ms, and amplitude 
≤ 100 mA. We will start stimulation at a low amplitude (e.g. 1 mA) and slowly increase 
amplitude to avoid inducing pain. If we identify stimulation parameters that are painful, we 
will cease stimulation above that amplitude. The transcutaneous electrical stimulation will 
be delivered intermittently for the duration of testing, in a pattern of 5-10 seconds ‘ON’ for 
the pulses, followed by 30-50 seconds ‘OFF’. 
2.4.2.19 EEG, EMG, and ultrasound studies 
Non-invasive electroencephalography (EEG) and electromyography (EMG) will be used 
during the study to measure neural and muscular responses to electrical stimulation. For 
EEG studies, electrodes will be placed on the surface of the scalp and, for EMG studies, 
electrodes will be placed on the surface of the skin on both the residual and contralateral 
limbs and the trunk. Stimulation will be applied as described above. We may also utilize 
ultrasound imaging to confirm the identity of muscle responses. A portable ultrasound 
probe will be used to scan over electrodes detecting muscle activity of participant's limbs. 
2.4.2.20  Effects on phantom limb sensation and pain 
Periodically throughout the experimental sessions, we will ask each subject to rate their 
current phantom limb pain from 0-10 on a visual analog scale, and to describe any 
subjective effects of stimulation on their phantom limb sensations and pain. We will also 
administer the pain portion of the Trinity Amputation and Prosthesis Experience Scales and 
the McGill Pain Questionnaire before device placement, at least once during the 90-day 
testing portion of the study, and again within a month after device removal. Other similar 
questions may be developed to best capture the effect of stimulation. 
2.4.2.21  Control of a prosthesis with somatosensory feedback 
During some sessions, participants will be asked to utilize a prosthesis with and without 
sensory stimulation. The prosthesis may be their own device, for assessing balance and 
gait, or virtual reality limb or device provided by the lab, for assessing proprioception. 
Testing will be at PI discretion and will depend on experimental goals, technical set-up, 
and participant availability. When physical devices are used, they will be instrumented 
with sensors that measure signals such as pressure, force, and joint angle. Signals from 
those sensors will be used to modulate stimulation. Any sensors placed on the participant’s 
prosthesis will be easily attached to the device and removed at the end of the session. To 
control the prosthetic or virtual limb, EMG signals will be recorded from the muscles in 
the residual limb using surface electrodes and/or limb motion of the intact and amputated 
limbs will be measured with an optical or magnetic motion tracking system and markers 
taped to the skin or clothing. Participants will be asked to perform tasks that test their 
ability to utilize sensory stimulation such as moving their limb to a specific point in space 
or applying a specified force through the limb. 
2.4.2.22  Balance and gait assessment 
To further evaluate the effects of sensory restoration on balance control and gait stability, 
we will also perform a battery of clinically validated balance and gait stability metrics. 

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Assessments include but are not limited to the Sensory Organization Test (SOT), 
Functional Gait Assessment (FGA), and the Amputee Mobility Predictor (AMP). Metrics 
will be performed with and without stimulation to determine the effects of sensory 
restoration on balance control. 
In the SOT, study participants stand on a platform that can impart translational and 
rotational perturbations at the feet, and key elements of sensory feedback (e.g. visual 
feedback, ankle proprioception) will be manipulated. By providing sensory feedback that is 
either unreliable or incongruent with the actual perturbation, the test provides a method for 
isolating the influence of somatosensory, visual, and vestibular inputs on balance. This test 
has been used to investigate balance control in individuals with lower-limb amputation2–5 
and there is evidence that an amputee's ability to balance serves as a valid indicator of their 
fall risk2 as well as their level of engagement in physical and social activities6. 
The impact of sensory stimulation on walking can be quantified using Functional Gait 
Assessment (FGA). The final score of this metric has been demonstrated to correlate with 
risk of falling7. The FGA includes ten modules that evaluate gait on level surfaces with 
variable speed, horizontal and vertical head turns, obstacles, pivots, with narrow base of 
support, with eyes closed, and while ambulating backwards6. Implementation of the 
assessment involves an expert reviewer who scores each task for levels of impairment, 
walking path deviations, changes in velocity, stumbles, and losses of balance7.  
The AMP can be used to the functional effects of sensory restoration8. The AMP 
encompasses many factors that contribute to an amputees’ ability to ambulate with a 
prosthesis. The AMP is scored by an expert reviewer as the participant performs a number 
of activities including rising from a investigate chair, transferring between chairs, standing 
balance, single limb balance, standing reach, initiation of gait, and stepping over obstacles 
and stairs8. 
We will also perform posturography to quantify static standing balance2. During this 
assessment, subjects will stand quietly on an instrumented force-plate while we record 
center of pressure under the feet. By quantifying changes in the movement of center of 
pressure over time, we can assess changes in static stability with sensory stimulation. 
We will also perform posture and gait analyses, in which subjects will stand or walk while 
wearing optical motion capture markers to measure the kinematics and kinetics during 
quiet standing and gait.  
All balance and gait experiments will be performed either under the direct supervision of a 
physical therapist or with the use of a safety harness system. Balance and gait experiments 
may be performed prior to device placement and up to one month after device removal as 
well as throughout the implant duration of the study. 
2.4.2.23  Electrode impedance 
Periodically during experimental sessions, we will measure the impedance of the SCS 
leads as a means to ensure that the device is functioning properly. This functionality is 
included in the Abbott External Pulse Generator and the Ripple stimulator. 

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2.4.2.24 Clinic-based prosthetic training and assessment  
Prior to each subject using the SCS-LLA system in the community outside the lab 
environment, one preliminary visit to the University of Pittsburgh’s Physical Therapy 
Clinical and Translational Research Center (PT-CTRC) will be completed to determine the 
participant’s baseline mobility, independence and function. This may include, but is not 
limited to, any relevant clinical evaluations of static and dynamic standing balance, gait 
and stairs. The participant’s ability to perform transfers (sit to stand, stand to sit, etc.) may 
be assessed. These evaluations will not only serve as a baseline assessment of function, but 
will also determine the duration and type of training that will be required with the 
sensorized prosthesis. 
Following SCS device placement and after stimulation parameters were selected for the 
SCS-LLA system, the participant will undergo 1-5 sessions of physical therapy and gait 
training with the SCS-LLA system and sensors attached to their prosthesis prior to the start 
of the community-use period. The duration of this training period will depend on the 
participant’s baseline level of function and independence, their progression throughout the 
training, and the clinical judgement of an experienced physical therapist. During this 
period, the participant will perform tasks requiring varying levels of balance and dynamic 
stability in order to best prepare him or her for changes in environment during community 
use of the system. The primary purpose of this physical therapy assessment is to determine 
whether the participant can safely utilize the system independently.  
In order to safely utilize the SCS-LLA system without assistance or supervision, the 
participant must be able to perform all necessary activities of daily living with modified 
independence (refer to checklist attached in Appendix E). Modified independence 
indicates that the participant is independent with the use of an assistive device. The 
participants must be able to safely maneuver curbs and thresholds. If the participant has 
stairs, either to enter or within their home, they should be able to ascend and descend steps 
independently, allowing the support of an assistive device or hand rail, if available in their 
home environment. Gait on uneven surfaces, over obstacles and up/down ramps will be 
tested and practiced, as well. The Amputee Mobility Predictor will also be used after 
training to determine K-level. 
Assessment of functional independence and clinical judgement will be used to determine if 
the participant is safe to use the SCS-LLA system independently in the community. If the 
subject is determined to be a K-1 ambulator after training, they will be instructed to only 
use the SCS-LLA system within their home. K-2, -3, and -4 ambulators will be allowed to 
use the SCS-LLA both in the home and in the community. If, following 5 days of physical 
therapy, the participant is still not safe to use the system independently, in-laboratory 
testing with the SCS-LLA system will continue and the participant will not complete the 
week-long unsupervised portion of the community-use trial. 
2.4.2.25 Technical training and assessment  
Prior to each subject using the SCS-LLA system unsupervised in the community outside of 
the lab environment, they will undergo training with lab staff on the proper use of the 
system, including techniques for donning and doffing, proper operation, calibration, and 
approaches for responding to system errors. Subjects will be instructed on various 
operating techniques, including: 

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• Connecting each component of the system and managing cables to avoid tangling 
or snagging on environmental hazards. 
• Charging external batteries and connecting them to the Nomad 
• Turning the system on and off and switching between operating modes (e.g. 
standby, calibration mode, active/stimulation mode) 
• (Optional) Operating the smartphone application and using it to understand system 
state information (e.g. battery status) and control system parameters (e.g. enter 
calibration state, adjust peak stimulation intensity) 
• Calibrating the system 
• Responding to various error states (e.g. low battery, no stimulation, unexpected 
stimulation) 
Before subjects are cleared for unsupervised community use of the system, lab staff will 
evaluate their understanding of system operations and approaches for responding to system 
error states, using the checklist in Appendix E. Supervised technical training may occur in 
the lab environment as well as during the two-week community use trial; however subjects 
will not be cleared for unsupervised community use until they have successfully 
demonstrated understanding of safe operating principals of the system. 
2.4.2.26 Community use of SCS-LLA system 
Subjects may participate in up to two weeks of community use of the SCS-LLA system 
and sensors applied to the exterior of their own prosthetic limb, including up to one week 
of unsupervised community use. Initially, during a period lasting no more than two weeks, 
subjects will engage in supervised community use of the system to gain experience with its 
operation and understanding of how to don/doff the system and how to respond to error 
conditions. After successfully completing clinic-based prosthetics training and assessment 
(Section 2.4.2.23) and technical training and assessment (Section 2.4.2.24), subjects will 
be cleared to participate in up to one week of unsupervised community use of the system. 
The total duration of supervised and unsupervised community use will not last longer than 
two weeks. During community use of the SCS-LLA system, data will be automatically 
collected by the external system. These data may include, but are not limited to, time of 
use, system state and error information, button presses, all sensor signals recorded by the 
system, and the timing and amplitude of all stimulation pulses delivered by the system. All 
data will be stored in a password protected file system inside the portable stimulation 
system (See Section E for more information). During the community use trial, subjects 
may also participate in lab-based testing such as balance and gait assessment, measurement 
of phantom limb pain, or sensory psychophysics. 
2.4.2.27  Removal of SCS leads 
After completion of testing and no later than 90 days after device placement, the SCS leads 
will be removed. Within two weeks prior to removal, at physician discretion, we may 
do other bloodwork, such as a complete blood count with differential and platelets; a 
prothrombin time and international normalized ratio; an activated partial thromboplastin 
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explant based on physician discretion. A MRSA screen will be also be done to determine 
what antibiotics will be used during the procedure.  
The subject will be taken to the procedural room or operating room at UPMC Mercy and 
placed on their stomach. As with implantation, an anesthesiologist may administer a mild 
anesthetic or general anesthesia. Prophylactic antibiotics (cefazolin and/or vancomycin, 
depending on MRSA status) will be intravenously administered approximately 30 minutes 
before the procedure. The sterile dressings for both the lead exit site and needle entry sites 
will be removed. We will apply sterile prep and drape to both the lead exit site and the 
needle entry site. The study neurosurgeon will then use a scalpel to open each of the needle 
entry sites. He will use surgical equipment to bluntly dissect at each level to the 
thoracolumbar fascia. Each of the anchoring devices attached to the percutaneous leads 
will be removed. The percutaneous leads will be removed from the epidural space and skin 
exit site. A study physician will inspect each lead to ensure that it is intact and was 
completely removed from the body. If there are any concerns about incomplete removal, 
fluoroscopic imaging can be used intraoperatively to visualize the epidural space and guide 
decisions about next steps, which will be determined by the neurosurgeon (e.g. additional 
surgical dissection to remove the remaining portion of the leads). The neurosurgeon and/or 
a neurosurgery resident will suture each of the needle entry sites in the skin and 
subcutaneous tissues; a sterile dressing will be applied to the area. The patient will be taken 
to recovery. This procedure is commonly performed at the end of percutaneous SCS trials 
and has a low rate of complications. 
2.4.2.28  Lead removal follow-up and monitoring 
We will monitor participants following lead removal to ensure healing of the lead removal 
site and to track any remaining changes in sensation or pain. A research team member will 
contact the participant once within 48 hours and again within one month of electrode 
removal to discuss changes in sensations associated with phantom limb pain.  Research 
staff will also ask the participant questions regarding general wellness and if they are 
experiencing any side effects associated with lead removal and infection, including 
bleeding, redness, swelling, or fever. Additionally, after the lead removal procedure and 
follow-up call, the participant will meet with a study physician. The timing of this visit is 
at the discretion of the physician but will be within three weeks after explantation. At this 
visit, the physician will remove any remaining sutures and examine the removal site for 
proper healing and signs of infection. Any cases of suspected of infection will be discussed 
with Infectious Disease and study physicians will follow all Infectious Disease directives. 
A neuropsychologist will also have a follow-up evaluation approximately 3-4 weeks after 
explant. A neuropsychologist will evaluate the participant’s psychological state at this time 
to determine if a referral for further clinical help during the transition period following 
explant is necessary. 
2.5 Study outcome evaluations 
2.5.1 Study endpoints 
The SCS leads will be removed no later than 90 days after implantation. The primary 
safety endpoint will be that there are no serious device-related adverse events. The 
secondary safety endpoint will be to determine the type and frequency of device-related 

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adverse events measured of the 90-day period following implantation. The primary 
efficacy endpoint for this study will be demonstration of the ability to evoke sensations 
localized to at least three focal regions of the missing foot and shank (e.g. lateral forefoot, 
medial forefoot, and heel). The secondary efficacy endpoints will be an improvement in 
balance control and gait stability and a reduction in phantom limb pain. Balance control 
and gait stability will be measured by a 10-point improvement in the Sensory Organization 
Test or a 6-point improvement in Functional Gait Assessment. A reduction in phantom 
limb pain will be measured by a 5-point improvement in the McGill Pain Questionnaire.  
2.5.2 Study ending or halting due to safety 
Subjects will be under medical supervision for the duration of this study and their health 
will be the top priority. Study physicians will be primarily responsible for evaluating a 
subject’s medical condition. Study complications that may adversely affect a subject’s 
health will consequently lead to the removal of the electrodes and ending of a subject’s 
participation. Complications that could result in the removal of stimulation leads include: 
• Lead migration that prevents the evocation of sensation in the missing limb 
• Lead breakage 
• Signs of systemic infection 
• Unresolved local infection at the lead site 
• Changes in subject’s medical status that could affect eligibility 
• Non-compliance with study procedures, including temperature monitoring, care of the 
implant sites, and attending testing sessions and clinical exams 
We may halt the study and reevaluate our protocol and risk mitigation procedures due to 
the occurrence of multiple adverse events. Adverse events that could result in the halting 
of the study and re-evaluation of study protocol include: 
• Two incidents of unresolved superficial infection resulting in lead removal 
• One incident of deep infection 
• One or more inpatient hospitalizations of subjects 
• Two or more subjects who withdraw from the study due to worsening pain or 
intolerable dysesthesia 
• One or more subjects who suffer a fracture due to falls related to the study 
interventions 
2.5.3 Sample size determination 
A maximum of 15 participants will be enrolled in order to achieve a maximum of 10 
subjects undergoing study procedures. Because it is possible that a subject may enroll and 
then be determined to be ineligible for placement of the spinal cord stimulator leads, the 
maximum number of subjects enrolled may exceed the number of subjects who undergo 
lead placement. 

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This is one of the first studies to evaluate sensory perceptions during spinal cord 
stimulation in lower-limb amputees. Because this is a feasibility study, we feel that it is 
appropriate to begin with a small sample size in this initial investigation. 
2.5.4 Outcome data and data analysis 
The primary outcome measure of the study will be safety. We will track the rate of adverse 
events to monitor safety of the study. The primary efficacy outcome will be quantification 
and evaluation of the types of sensory percepts evoked by spinal root stimulation, as well 
as the anatomical locations to which those percepts are referred. Additionally, we will 
record any subjective changes in the perception of phantom limb sensations or phantom 
limb pain during and following spinal root stimulation. We will quantify differences in the 
ability to control a prosthetic limb with and without sensory stimulation. We will compare 
the balance and gait assessment scores of individuals using the SCS-LLA system and 
community-use of stimulation with the scores of subjects who underwent lab-only testing 
in our ongoing study to quantify the effects of extended access to the device.   
New information will be learned with each participant, as this is a pilot study. Single-
subject design statistical analyses will be used. Our main goals are to demonstrate device 
safety as well as the feasibility of using spinal root stimulation to evoke realistic sensory 
percepts referred to the foot and leg in individuals with lower-limb amputation, and to 
document any effects of that stimulation on phantom limb sensations and phantom limb 
pain. We will quantify the threshold for producing a just-noticeable sensory percept, as 
well as the relationships between stimulation parameters and evoked sensations when 
stimulating through individual electrodes or combinations of multiple electrodes. 
To fulfill Specific Aim 1, we will document adverse events that occur during the study. We 
will report adverse events to the local Institutional Review Board and to the FDA in 
accordance with the respective reporting requirements. This documentation will serve as 
demonstration of the safety of the SCS-LLA system in this small sample. 
To fulfill Specific Aim 2a, in which we quantify the threshold for evoking a sensory 
percept, we will use regression analysis to examine differences in stimulation thresholds 
related to a variety of factors. Examples of these factors include the anatomical location of 
each electrode (based on fluoroscopic imaging), level of amputation, time since 
amputation, level of pre-intervention phantom limb sensation and pain, and the thresholds 
of nearby electrodes. 
With respect to Specific Aim 2b, the results will produce descriptive anatomical maps of 
the modalities and locations of sensory percepts evoked by spinal root stimulation. These 
maps will allow us to examine the specificity of stimulation through individual electrodes 
as well as the overall coverage of the evoked sensory percepts across the entire amputated 
limb. The results of Specific Aim 2c will be a set of purely descriptive statements made by 
the subjects that will provide additional insight into their experience with SCS and their 
preferences for this type of neuroprosthetic intervention.  
The results of Specific Aims 3a and 3b will be a combination of descriptive statements on 
the subjective experience of SCS and its effects on phantom limb sensations and pain, as 
well as a data set including perceived pain ratings from a visual analog scale at multiple 
time points before and during the experimental study. These pain-rating results will be 

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compared within each subject and across subjects via regression analysis to determine if 
there is any effect of spinal root stimulation on phantom pain levels.  
The results of Specific Aims 4 and 5 will be a data set including EMG, kinematics, and 
performance metrics that will allow us to quantify the subject's ability to control a 
prosthetic limb with and without sensory stimulation. Kinematic and performance metrics 
data will be compared within and across subjects using regression analysis to quantify 
changes in control with the addition of sensory stimulation. 
With respect to Specific Aim 6, we will utilize analysis of variance to compare balance, 
gait, and pain scores before and after the trial of community use. 
3.0  Risk Analysis 
3.1 Anticipated risks 
This study involves potentially serious risks. The risks of all experimental procedures are 
described below along with the steps that will be taken to minimize those risks. 
Application of Anesthetic: 
There is a risk of increased pain and/or local infection at the injection site. Additionally, because 
Lidocaine will be injected into the skin and the surrounding tissues prior to SCS lead placement, 
there is a low risk of adverse reactions including light headed-ness, dizziness, drowsiness, 
blurred vision, respiratory depression, edema, low blood pressure, and/or irregular heartbeat.  
Steps taken to minimize these risks: 
Subjects will be asked about any known allergies or previous reactions to lidocaine or similar 
anesthetics before the procedure. Further, the subject will be monitored throughout the device 
placement process and experimental procedures for adverse reactions to the anesthetic.  
 
Application of General Anesthesia: 
  There are risks of side effects such as such as nausea, vomiting, chills, confusion for a few days, 
a sore throat caused by a breathing tube, breathing problems including pneumonia, and injury to 
the teeth. 
Steps taken to minimize these risks: 
General anesthesia will be only be used if the patient requests it and the anesthesiologist 
approves it. Subjects will be asked about any known allergies or previous reactions to general 
anesthesia before the procedure. Further, the subject will be monitored throughout the 
surgical procedure for adverse reactions to the anesthetic. The anesthesiologist will also be 
monitoring the participant’s vital functions and breathing. 
  
Blood Draw for Pre-Operative Screening: 
The insertion of the needle to draw blood may cause temporary discomfort, bruising at the 
insertion site, or soreness. There is a slight risk of infection. Fainting may occur but is expected 
to be rare, occurring in less than 1% of people. 

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Steps taken to minimize these risks: 
Pre-operative screening will be performed in the Physical Medicine & Rehabilitation 
department at UPMC or another pre-operative screening facility within the UPMC system, 
which are experienced at and maintain the proper environments for these types of procedures. 
EKG for Pre-Operative Monitoring: 
There is a risk of skin irritation after removal of the electrodes used for EKG monitoring. 
Steps taken to minimize these risks: 
Sensors will be removed with caution and care to prevent discomfort. 
Epidural Spinal Cord Stimulation: 
Uncomfortable sensations may be elicited as a result of stimulation. Involuntary movements, 
which subside after several minutes may be elicited. It is possible for high levels of stimulation 
to cause damage to neural tissue. 
Steps taken to minimize these risks: 
If a noxious or uncomfortable sensation is evoked in a participant as a result of stimulation, 
stimulation on that channel will cease. During stimulation trials, the stimulus charge will be 
increased slowly to allow self-reporting of any noxious sensations. If noxious sensations are 
evoked, the stimulus charged for that electrode will be limited to sub-noxious levels. To 
avoid tissue damage, stimulation parameters will stay at or below those described in the 
Section 2.4.2.15. 
Interactions between the SCS-LLA system and prostheses: 
There is a risk that electromagnetic or mechanical interactions between the SCS-LLA system and 
the prosthesis could cause malfunctions in either system. Examples of electromagnetic 
interactions include interference from an actively powered ankle joint on the wireless 
functionality of the Nomad or interference from the Nomad causing malfunctions in an actively 
powered prosthetic ankle. Examples of mechanical interactions include cabling from the SCS-
LLA system wrapping around the ankle joint causing the cable to break or the ankle joint to 
seize. 
Steps taken to minimize these risks: 
Most prosthetic ankle joints are passive, do not have any electrical components, and will not 
generate electromagnetic signals that could interfere with the SCS-LLA system. The newest 
generation of actively powered or micro-controller controlled ankles, such as the Ottobock 
Empower or Ossur Proprio Foot have extensive documentation on their electromagnetic 
compatibility. If we identify that a subject has an actively powered prosthesis that could 
interfere with operation of the SCS-LLA system, we will consult the manufacturer 
documentation for recommendations about avoiding interference. For example, the Ossur 
Proprio Foot manual states “Portable RF communications equipment... should be no closer 
than 30 cm (12 inches) to any part of the device...” Based on these recommendations, we 
may, for example, use a wired pressure sensitive insole, rather than a wireless one. Further, 
during initial use of the SCS-LLA system during standing and walking, a study investigator 
will stand near the subject to provide support in case of a fall. To avoid mechanical 

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interference between the prosthesis and the SCS-LLA system, all cabling will be kept as 
short as possible and will be routed under clothing and secured with tape whenever possible. 
If cables from the SCS-LLA system do snag and break, stimulation will stop and the 
prosthesis will continue to operate as normal without sensory feedback. 
Magnetic Resonance Imaging (MRI) with Contrast: 
The magnet utilized for MRI will make intermittent loud knocking noises that could cause 
discomfort in some subjects. The subject may experience feelings of anxiety or claustrophobia 
during the MRI scan. There is also a risk of the MRI scanner attracting metal objects. There is a 
risk of loosening of ferromagnetic objects that are affixed to bone. There is a risk of tissue 
heating for metallic implants. The contrast agent used during these MRI’s, gadolinium, is FDA-
approved and used routinely for MRI exams. The injection of contrast may cause discomfort, 
tingling, or warmth in the lips, metallic taste in the mouth, tingling in the arms, nausea, or 
headache. These symptoms occur in less than 1% of people and go away quickly. There is a 
small risk of an allergic reaction to gadolinium; however, a severe allergic reaction occurs in less 
than one in 300,000 individuals. Insertion of the needle to inject the gadolinium may cause minor 
pain, bruising, and/or infection at the injection site. People with severe kidney failure who 
receive gadolinium are at risk of developing Nephrogenic Systemic Fibrosis/Nephrogenic 
Fibrosing Dermopathy (NSF/NFD). This disease causes fibrosis, which is the formation of too 
much connective tissue in the skin and internal organs throughout the body. People develop skin 
thickening that may prevent bending and extending joints, resulting in decreased movement of 
the joints. The skin changes can cause feelings of burning, itching, and pain that can be severe. In 
addition, people may experience fibrosis that spreads to other parts of the body such as the 
diaphragm, muscles in the thigh and lower abdomen, and the lining of blood vessels in the lung. 
NSF/NFD is a serious progressive disease and can result in death. If the subject has severe 
kidney failure and receives gadolinium, the risk of developing NSF/NFD is 1-5%. We may 
require a blood sample (about 1 tablespoon) to check kidney function before gadolinium contrast 
is utilized. There is evidence that repeated MRI scans with gadolinium can result is some 
accumulation of it in the brain. The significant of this and possible effect on health is not known. 
Steps taken to minimize these risks: 
Steps will be taken to minimize potential discomforts due to noise in the MRI, such as 
wearing earplugs and informing the subject beforehand about these discomforts. Two-way 
communication will be available throughout the scan in case the subject experiences feelings 
of anxiety or claustrophobia. The study team, as well as the staff at the MRI center(s), will 
administer standard screening procedures prior to the scan to ensure the subject’s safety. 
Metallic implants, such as pacemakers or permanent piercings, are considered 
contraindications for MRI and may exclude potential participants. Any implanted metal will 
be investigated prior to MRI to determine its safety. Participants will be asked to notify a 
doctor, nurse, or technologist if they are allergic to gadolinium, if they have any kidney 
problems, or if they experience any other side effects. Individuals with renal failure or 
dysfunction will be excluded from study participation. A physician will be available during 
this procedure to administer any necessary care if side effects do occur, and to determine 
when or if the injection of gadolinium should be stopped. 

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Mechanical and/or Electrical Stimulation of the Residual and Contralateral Limbs: 
There are minor risks associated with the electrical and mechanical stimulation of the residual 
and contralateral limbs. These include uncomfortable sensations and irritation of the skin. As 
with EMG signal recording, sticky electrodes may be attached to the skin during electrical 
stimulation; these may cause skin irritation. 
Steps taken to minimize these risks: 
To avoid discomfort and skin irritation, we will ensure that the subject is aware that they may 
request to stop testing at any time. Further, we will work with the subject to ensure that we 
avoid repeating application of stimulation to the limbs that is excessively uncomfortable. 
Observing a Virtual 3-D Environment: 
Nausea or dizziness may result from wearing 3-D glasses in a virtual environment. 
Steps taken to minimize these risks: 
This risk will be mitigated by providing frequent breaks and adjusting task difficulty. 
Two-Week Community-Use Trial: 
There may be a risk of falling while walking/standing with the SCS-LLA system. There is a risk 
of system failure due to technical/software issues or power malfunction, which may cause 
distraction during walking, causing a fall. Falls may cause injuries ranging from minor (e.g. cuts, 
abrasions, bruises) to major (e.g. broken bones, head injury). The risks of interference between 
the SCS-LLA system and the subject’s prosthesis are the same as those described in the section 
“Interactions between the SCS-LLA system and prostheses” above. 
Steps taken to minimize these risks: 
To avoid interference between the SCS-LLA system and the user’s prosthesis, we will 
follow the mitigation procedures outlined in section “Interactions between the SCS-LLA 
system and prostheses” above. Prior to the unsupervised community-use portion of the trial, 
an engineer will train the subject on the technical aspects of the system, including device 
failure modes. An engineer will train subjects about the most likely types of failures and 
instruct them to contact us with any problems that may occur. Subjects will be shown how 
to turn the system on and off so that it can be powered off if it is not functioning properly. 
Once the system is off, whether due to powering off or battery failure, the subject's 
prosthesis will function as normal, greatly minimizing any negative effects resulting from 
technological issues. Additionally, we will provide between 1 and 5 training sessions with a 
physical therapist with expertise in lower-limb amputation, as well as evaluate the subjects' 
proficiency with the system, prior to completing the unsupervised community-use portion of 
the trial. While the subject is walking under the supervision of a physical therapist, we will 
intentionally turn the system off so they can experience this occurrence and how to properly 
respond.  These safety precautions will minimize the risk of falling to no more than is 
expected during normal day-to-day activities. 
Photographs and Audio/Video Recordings: 
There is a risk of identity theft or breach of confidentiality. 

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Steps taken to minimize these risks: 
We will take the necessary steps to protect personal identity and information. Photographs 
and videotapes will be stored digitally on our password-protected server; hard copies may be 
stored in a locked filing cabinet. 
Placement of Spinal Cord Stimulator Leads: 
According to the PMA that covers the Abbott Medical Spinal Cord Stimulation System, the most 
common adverse event is lead migration, which occurs in 13.6% of patients. Even in the case 
where lead migration occurs, the medical risk to the subject is low, with the more likely result 
being a change in the anatomical location of the perceived sensations. Other common risks 
include seroma and bruising at the placement site. The lead anchoring procedure performed by 
the study physician and neurosurgeon will minimize this migration. Additionally, we intend to 
examine the stability of the neurophysiological response to stimulation over the course of the 
experimental session and the effects that stability may have on the perceived sensations. The 
tables included in the Abbott Medical Spinal Cord Stimulation System PMA (Appendix C) list 
the rates of complications. Placement of the Tuohy needle and spinal cord stimulator leads could 
potentially result in nerve damage that can cause neurological dysfunction, including paralysis. 
Additionally, it is possible that a tear in the dura could occur, resulting in a spinal fluid leak or 
hemorrhage (refer to Appendix C; risk: 0.5%). A spinal fluid leak can cause headaches and, in 
rare cases, may require surgery. The placement of these devices is common clinical practice for 
treatment of intractable lower back and limb pain, and complications are rare. There is a low risk 
of meningitis and infection at the electrode placement site as a result of lead placement, though 
the use of sterile technique during device placement makes this risk low (Appendix C; risk: 
3.0%). 
Steps taken to minimize these risks: 
Placement of these devices is commonly done at UPMC Mercy by physician co-
investigators. Decolonization procedures for minimization of surgical site infection will be 
provided to the participant prior to surgery. These procedures include showering each of the 5 
days leading up to surgery, including the morning of surgery. Also, an ointment will be 
provided to use around the nose to minimize intake of bacteria into the body. After device 
placement and throughout the initial experimental session, the subject will be monitored for 
any adverse reactions to the device. At the time of discharge after implant and explant, the 
subject will be instructed on the signs and symptoms of nerve damage or spinal fluid leak and 
instructed to contact their physician if these symptoms occur. We will also follow up with the 
subject by phone within two days after lead removal to check for any symptoms of nerve 
damage or CSF leak. If surgery is required to correct a CSF leak, the costs will be covered 
through departmental funds from the Department of Physical Medicine & Rehabilitation. To 
minimize post-operative infection risk, IV cefazolin will be administered immediately before 
the lead placement procedure. If the subject is positive for MRSA via preoperative screening 
or has a history of MRSA, IV vancomycin will be used in addition to IV cefazolin. If the 
subject has a severe penicillin allergy, IV vancomycin will be used instead of IV cefazolin.  
Post-Operative Pain Medication (Norco 5-325 or Similar): 
Common risks associated with Norco 5-325 include drowsiness9. Infrequent risks include 
nausea, vomiting, constipation and/or diarrhea, pruritus, rash, dizziness, and confusion9. There is 

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also a risk of developing tolerance, physical dependency, and psychological dependency upon 
repeated and prolonged administration of narcotics. 
Steps taken to minimize these risks: 
Before the procedure, the subject will be asked about any known allergies or previous 
reactions to Norco 5-325 or similar pain medications. Pain medication will be prescribed for 
a short period of time and in limited doses to reduce the risk of developing tolerance or 
dependency. Prior to prescribing any narcotic pain medication, we will use the Screener and 
Opioid Assessment for Patients with Pain (SOAPP) questionnaire to evaluate risk of 
dependency. Subjects determined to be high risk will not be prescribed pain medication. The 
subject will be monitored during the first few weeks of the study following implant for signs 
of dependency and adverse drug reactions. 
Using the results from the SOAPP questionnaire, the following steps would be taken. 
SCORING: All 24 questions contained in the SOAPP®-R have been empirically identified as 
predicting aberrant medication-related behavior six months after initial testing. To score the 
SOAPP, add the ratings of all the questions. A score of 18 or higher is considered positive. 
RESULTS: If the score is less than 18, opiate medication may be prescribed. 
If the score is more than 18, the individual will be informed that opiate medication will not 
be used. Instead, Tylenol or a weaker opiate like Ultram (tramadol) may be prescribed. If the 
individual consents to this change, then the study and implantation of the device will 
continue. 
If opiate medication is used for pain relief, then a study physician will follow up by asking 
every week after implant how the patient is doing in terms of how often they’re using the 
medication, and counseling the individual on correct usage in terms of frequency. 
 
Presence of Spinal Cord Stimulator Leads: 
The risks associated with maintaining the sub-chronic placement of the spinal cord stimulator 
leads (for 90 days) are expected to be similar to those normally observed during clinical 
assessment of these devices for treatment of intractable low back or limb pain, although the risk 
of infection is likely higher because of the extended duration of the percutaneous implantation 
period. During normal clinical practice the devices are placed percutaneously near the spinal 
cord and maintained for approximately one week in the US10, or multiple weeks in Europe11, 
with good outcomes. Some of the risks associated with these procedures include, but are not 
limited to, pain at the electrode sites, allergic reaction in response to the implanted leads, CSF 
leak, lead migration resulting in undesirable changes in stimulation, lead breakage, tissue 
reaction, and spinal cord compression. Nerve damage causing neurological dysfunction and 
paralysis may also occur. The most common complications are lead migration, occurring in 
13.6% of patients, and infection. Because of the extended duration of the percutaneous 
implantation period, the risk of infection is likely higher than that reported by Abbott, which 
reflects the traditional week-long trials performed in the US. Instead, the risk is likely to be 
similar to other procedures in which percutaneous catheters are maintained for extended 
durations. One meta-analysis reported that intrathecal catheters for cancer pain management have 

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an infection rate of 1.4% for deep infections and 2.3% for superficial infections. Another meta-
analysis reported infection rates of 2% and 4% for deep and superficial infections, respectively. 
The outcome of infection may be serious and may lead to edema or other sequelae.  
Steps taken to minimize these risks: 
All device materials in contact with the body are known to be biocompatible materials. 
Because the leads protrude through the skin, there is a risk of infection throughout the study. 
The risk of infection is minimized by frequent checks of the site and a specific wound/skin 
care procedure designed to reduce the chance of infection. A sterile environment will be 
utilized during surgery, and individuals who may be at a high risk for infection (for example, 
those taking immunosuppressive drugs) will be excluded from the study. An antimicrobial 
silver dressing will be used and will be changed at least once every three days by a study 
physician, research staff member, or trained care-giver. We will provide detailed cleaning 
instructions to the participant and anyone who may assist with dressing changes. A study 
physician will complete a summary discharge document, of which the subject will receive a 
copy. During dressing changes, the subject or a caregiver will be instructed to inspect the site 
for redness or discharge. Participants will be asked to monitor their temperature at home, and 
temperature will be taken at each lab visit. A study physician shall be informed of a fever 
(>99.5 F). A physician will inspect the site at least once per week, or twice per week if 
vancomycin was the only antibiotic administered at the time of implant. If new redness is 
seen, blood work will be performed to look for possible signs of infection (e.g. CBC, CMP, 
CRP, ESR). If there is a suspected superficial infection and there are no signs of systemic 
infection (e.g. abnormal blood work, fever, chills), the incision sites will be swabbed and 
cultured and the subject will be prescribed a 5-7-day course of oral antibiotics. If the 
infection does not improve with three days of oral antibiotics, the lead(s) at the infected site 
will be removed. If any sign of systemic infection is detected or if there is a discharge at the 
incision site suspicious for infection (yellowish-white and/or viscous), the lead(s) will be 
removed. In any case of suspected infection, an expert in Infectious Disease at UPMC will be 
consulted by study physicians and IV antibiotics recommended by Infection Disease will be 
administered. If the devices migrate to a position where they are no longer functionally 
useful (i.e. they no longer produce sensations referred to the amputated limb), the devices 
will be removed and testing will cease. If lead breakage is suspected, the devices will be 
visually inspected during removal, and if necessary, fluoroscopic or x-ray images will be 
acquired to determine if complete removal occurred. At the neurosurgeon’s discretion, 
additional surgical intervention may be required to remove lead fragments in the case of lead 
breakage. 
Procedural Sedation: 
Common risks of sedation with intravenous Fentanyl include nausea and vomiting, urinary 
retention, and pruritus12. Respiratory depression may occur, although literature reports indicate 
that most of these events are not significant12. Infrequent risks of Versed (midazolam) use include 
respiratory depression and temporary hypotension13. 
Steps taken to minimize these risks: 
Before the procedure, the subject will be asked about any known allergies or previous 
reactions to Fentanyl and Versed. An anesthesiologist will be present to ensure subject safety. 

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Medical staff at UPMC Mercy will closely monitor subjects during and after the lead 
placement procedure. 
Prophylactic Antibiotics (Cefazolin or Similar): 
Allergic reactions, including itchiness, are possible depending on each individual and their 
reported history. Seizure, fever, rash, itching, diarrhea, C. difficile infection, nausea, vomiting, 
increased liver enzymes, and abnormal blood urea nitrogen or serum creatinine levels are 
considered infrequent risks. 
Steps taken to minimize these risks: 
Before the procedure, the subject will be asked about any known allergies or previous 
reactions to Cefazolin or similar antibiotics. The subject will be monitored for adverse 
reactions to the antibiotic. 
Recording of Personal Information, text messaging and Bluetooth transmission from device: 
There is a risk of breach of confidentiality since personal information will be obtained. 
Steps taken to minimize these risks: 
Identifiable data will be filed in locked areas immediately after collection. Study ID numbers 
will be used instead of the participant’s name when recording study-related data. The 
information collected in this study, such as psychophysical data, will generally consist of 
numbers with little or no meaning to the casual observer. Electronic data is stored on 
password-protected network drives. Staff have been trained regarding the critical nature of 
participants’ privacy, as well as about procedures for respecting their privacy and maintaining 
confidentiality. 
Securing Electrodes and Leads to the Skin with Adhesive and/or Tape: 
Removing tape from skin may cause discomfort. Adhesive and/or tape may pull hair from the 
skin and result in discomfort. 
Steps taken to minimize these risks: 
Tape will be used conservatively and will be removed with caution and care. 
Spinal Cord Stimulation Electrodes Connected to Incorrect Stimulator Channels: 
It is possible that a study investigator may incorrectly connect the percutaneous SCS leads to the 
wrong stimulation channels, resulting in stimulus pulses being delivered to the incorrect 
electrodes. This would cause aberrant feedback and could evoke painful sensations. 
Steps taken to minimize these risks: 
Each percutaneous lead will be clearly labeled with a unique identifier (e.g. a red, green, or 
yellow colored flag), which will be connected to a matching identifier on the stimulator 
connector. In the case that the connectors are swapped, stimulation will still always be 
delivered at levels within the 30 µC/cm2 safety limit, so no tissue damage will occur. If a 
subject feels an unpleasant or unexpected sensation, they will be instructed to notify research 
staff. 

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Standing and Walking with Sensory Feedback Provided by Spinal Root Stimulation: 
It is possible that subjects may find sensory feedback disorienting or distracting during standing 
and walking. Aberrant feedback may cause an inappropriate response to postural perturbations, a 
loss of balance, or falls.  
Steps taken to minimize these risks: 
During initial use of stimulation for sensory feedback during standing and walking, a study 
investigator will stand near the subject to provide support in case of a fall. During testing of 
postural stability and balance control, a physical therapist will stand near the subject or a 
harness will be used to protect against falls. 
Structural MRI without Contrast: 
The magnet will make intermittent loud knocking noises that may cause discomfort in some 
people. We may ask the subject to wear a neck brace during these scans to ensure that the spine is 
in the same position for both the CT and the MRI. Subjects may feel discomfort wearing the 
brace. The subject may experience feelings of anxiety or claustrophobia during the MRI scan. 
There is also a risk of the MRI scanner attracting metal objects. There is a risk of loosening 
ferromagnetic objects affixed to bone. There is a risk of tissue heating for metallic implants. 
Steps taken to minimize these risks: 
Steps will be taken to minimize potential discomforts due to noise in the MRI, such as 
wearing earplugs and informing the subject about the procedures. Two-way communication 
will be available throughout the scan in case the subject experiences feelings of anxiety or 
claustrophobia. The MRI scanner may attract metal objects. Some metallic implants, 
pacemakers, and other metallic substances are considered contraindications for MRI and 
therefore may exclude someone from participating in this study. Any implanted metal will be 
investigated to ensure that it is not unsafe for MRI. The MRI center will also perform their 
standard screening procedures prior to the scan to ensure the subject's safety. 
Removal of SCS Leads/Lead breakage: 
There is a risk of post-implantation infection of the skin where the electrodes were placed. 
Meningitis is also a rare but potentially serious risk. The risks of infection may increase the 
longer the electrodes remain implanted. 
Steps taken to minimize these risks: 
 
If lead breakage is suspected, the devices will be visually inspected during removal, and if 
necessary, fluoroscopic or x-ray images will be acquired to determine if complete removal 
occurred. At the study physician’s discretion, additional surgical intervention may be 
required to remove lead fragments in the case of lead breakage. Participants will meet with 
study physicians within three weeks following removal to check for signs of infection. 
Research staff will additionally follow-up with participants via phone call 48 hours and 

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within one month after removal to monitor recovery. 
 
Please note that the following procedures utilize radiation. There is no minimal level of radiation 
exposure that is recognized as being totally free of the risk of causing genetic mutations or cancer. 
However, the risk associated with the amount of radiation exposure that the subject will receive 
from these procedures is below 50 mSv, which is the annual radiation exposure limit for radiation 
workers. 
 
Fluoroscopy Guided Lead Placement and removal: 
The lead placement procedure occurs under fluoroscopic guidance, which involves radiation 
exposure. The radiation exposure associated with this procedure is expected to be approximately 
10 mSv.  Although unlikely, fluoroscopy could also be used during lead removal if a lead breaks. 
In this case exposure is expected to be of a much shorter duration, with radiation exposure of 
approximately 1-2 mSv. For reference, federal regulations allow an annual radiation exposure of 
50 mSv to the most sensitive organs of radiation workers. There is no minimal level of radiation 
exposure that is recognized as being totally free of the risk of causing genetic mutations or 
cancer.  
Steps taken to minimize these risks: 
Imaging is required during placement of the spinal stimulator leads. The risk associated with 
the amount of radiation exposure that the subject will receive from this additional x-ray exam 
is below 50 mSv, which is the annual radiation exposure limit for radiation workers. At the 
end of the study, we will notify subjects of their effective radiation exposure dose during the 
study and will instruct them to notify their doctor of this dose prior to any additional imaging 
for 12 months following study participation.High Resolution CT Scan of the Lumbar Spine: 
The maximum amount of radiation exposure that participants will receive from the high-res CT 
is 6 mSv  which is less than the annual radiation exposure (50 mSv) permitted to the most 
sensitive organs of radiation workers by federal regulations.  
Steps taken to minimize these risks: 
The risk associated with the amount of radiation exposure that the subject will receive from 
the CT scan is below 50 mSv, which is the annual radiation exposure limit for radiation 
workers. At the end of the study, we will notify subjects of their effective radiation exposure 
dose during the study and will instruct them to notify their doctor of this dose prior to any 
additional imaging for 12 months following study participation.Optional X-Ray for MRI 
Clearance 
 
The maximum amount of radiation exposure that participants will receive from this x-ray is 1 
mSv. This is a fraction of the annual radiation exposure (50 mSv) permitted to the most sensitive 
organs of radiation workers by federal regulations. There is no minimal level of radiation 
exposure that is recognized as being totally free of the risk of causing genetic mutations or 
cancer. However, the risk associated with the amount of radiation exposure that the subject will 
receive from these x-rays is considered to be low and comparable to everyday risks. 
 

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Steps taken to minimize these risks: 
The risk associated with the amount of radiation exposure that the subject will receive from 
these x-rays is below 50 mSv, which is the annual radiation exposure limit for radiation 
workers. At the end of the study, we will notify subjects of their effective radiation exposure 
dose during the study and will instruct them to notify their doctor of this dose prior to any 
additional imaging for 12 months following study participation.Chest X-ray for Pre-
Operative Screening: 
The maximum amount of radiation exposure that participants will receive from 2 views of chest, 
x-ray is 0.01 mSv. This is lower than the annual radiation exposure (50 mSv) permitted to the 
most sensitive organs of radiation workers by federal regulations. There is no minimal level of 
radiation exposure that is recognized as being totally free of the risk of causing genetic mutations 
(abnormal cells) or cancer. However, the risk associated with the amount of radiation exposure 
that the subject will receive from this x-ray exam is considered to be low and comparable to 
everyday risks. 
Steps taken to minimize these risks: 
The risk associated with the amount of radiation exposure that the subject will receive from 
these x-rays is below 50 mSv, which is the annual radiation exposure limit for radiation 
workers. At the end of the study, we will notify subjects of their effective radiation exposure 
dose during the study and will instruct them to notify their doctor of this dose prior to any 
additional imaging for 12 months following study participation.. 
Thoracic and/or Lumbar X-Rays for Documentation of Lead Location and Migration: 
The maximum amount of radiation exposure that participants will receive from each multi-view 
x-ray of the thoracic spine is 1 mSv, and the lumbosacral spine is 1.5 mSv. Participants will 
receive multi-view x-rays for the first four weeks following implantation, and then multi-view x-
rays biweekly for the remainder of the study, for a total of eight x-rays and a maximum exposure 
of 20 mSv. This is a fraction of the annual radiation exposure (50 mSv) permitted to the most 
sensitive organs of radiation workers by federal regulations. There is no minimal level of 
radiation exposure that is recognized as being totally free of the risk of causing genetic mutations 
or cancer. However, the risk associated with the amount of radiation exposure that the subject 
will receive from these x-rays is considered to be low and comparable to everyday risks. To 
minimize radiation exposure, we will only collect both thoracic and lumbosacral x-rays if the 
leads cannot be visualized with only one of the two images. 
Steps taken to minimize these risks: 
Imaging studies are necessary to document any movement of the stimulator leads over the 
course of the study. The risk associated with the amount of radiation exposure that the subject 
will receive from these x-rays is below 50 mSv, which is the annual radiation exposure limit 
for radiation workers. At the end of the study, we will notify subjects of their effective 
radiation exposure dose during the study and will instruct them to notify their doctor of this 
dose prior to any additional imaging for 12 months following study participation. 

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Sponsor-Investigator: Lee Fisher, PhD 
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3.2 Summary of risks and justification related to the use of spinal cord stimulation 
The primary risk for a study of chronically placed electrodes is infection. However, current 
statistics show that this risk is quite low (6%). Infection risk is further minimized through the use 
of frequent checks by the physicians and study team, a specific wound/skin care procedure 
designed to reduce the chance of infection, and the administration of prophylactic antibiotics on 
the day of lead placement. The General Health Questionnaire mentioned previously also provides 
the study team with pertinent medical information, allowing us to exclude individuals who may 
be immunosuppressed and/or at a higher risk of infection. 
There is also a risk of falling when performing tasks with the SCS-LLA system. This risk will be 
minimized by supervision of the subject by a physical therapist during in-lab testing and 
substantial training and assessment before unsupervised use of the system. 
4.0 Description of the Device 
4.1 Belt-worn stimulator and data acquisition system 
Ripple has recently begun marketing a belt-worn system, called the Nomad Research System, 
that has undergone extensive safety and EMC testing, per IEC 60601-1 and 60601-2, and can be 
used in clinical trials under IRB approval to process and analyze sensor data and generate trains 
of stimulus pulses. A set of external sensors will be connected to the Nomad and stimulus 
encoding algorithms will run on a connected PC or on the Nomad’s internal processor. Signals 
will be sampled by the Nomad’s A/D board or will be transmitted wirelessly to the Nomad (e.g. 
via Bluetooth). A set of custom adapters will be used to connect the Nomad stimulation front-
ends to the Abbott Spinal Cord Stimulator Leads. For more detail on the Nomad and its 
components, see Section E. 
4.2 Spinal cord stimulator leads 
Abbott Medical is currently marketing their Spinal Cord Stimulation system, a neurostimulation 
system that includes 8-contact leads designed for percutaneous and permanent implantation. The 
off-label approach used in this study is nearly identical to the FDA-cleared procedure (PMA 
P010032 and 510(k) K960728) in which these devices are placed in the epidural space for 
treatment of chronic intractable pain of the trunk and/or limbs. As in that procedure, the device 
will be tunneled percutaneously through the skin and secured in place, then removed at the end 
of the study. The devices will be placed during a fluoroscopically guided outpatient procedure, 
which typically takes 3-4 hours, and kept under the skin for no more than 90 days. The leads 
used in this study have been designed and tested for permanent implantation and contact with the 
body for >90 days. Removal will be accomplished by a physician during a visit to UPMC Mercy. 
We will target the appropriate regions of the spinal cord by using the catheter included with the 
device to steer it in the epidural space. The proposed study is intended to evaluate the safety of 
the integrated system, as well as to characterize the types of sensations that can be evoked by 
stimulation of the spinal cord. We will implement software limits to ensure that stimulus 
parameters remain within the limits described in the Abbott PMA and 510(k). Monitoring 
Procedures 

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Sponsor-Investigator: Lee Fisher, PhD 
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4.3 University of Pittsburgh Education & Compliance Office – Human Subject Research 
Independent monitoring of the clinical study for clinical protocol and IDE application 
compliance will be conducted periodically (i.e., at a minimum of annually) by qualified 
staff of the University of Pittsburgh’s Education and Compliance Office – Human Subject 
Research. The address is listed below. Monitoring procedures are listed on the office 
website at http://www.ecohsr.pitt.edu/ . 
Education and Compliance Office – Human Subject Research 
University of Pittsburgh, Office of Research Protections 
Hieber Building, Suite 205 
3500 Fifth Avenue, Pittsburgh, PA 15213 
The sponsor-investigator and the University of Pittsburgh and University of Pittsburgh 
Medical Center will permit direct access of the study monitors and appropriate regulatory 
authorities to the study data and to the corresponding source data and documents to verify 
the accuracy of this data.  
4.4 Data Safety Monitoring Board 
An independent Data and Safety Monitoring Board (DSMB) has been established to 
review this study. After this approval and at periodic intervals (to be determined by the 
board) during the course of the study, the DSMB responsibilities are to: 
1. Review the research protocol, informed consent documents and plans for data and 
safety monitoring; Evaluate the progress of the study, including periodic assessments of 
data quality and timeliness, participant recruitment, accrual and retention, participant risk 
versus benefit, performance of the trial site, and other factors that can affect study 
outcome; 
2. Consider factors external to the study when relevant information becomes available, 
such as scientific or therapeutic developments that may have an impact on the safety of 
the participants or the ethics of the study; 
3. Review clinical center performance, make recommendations and assist in the 
resolution of problems reported by the PI; 
4. Protect the safety of the study participants; 
5. Report on the safety and progress of the study; 
6. Make recommendations to the PI, IRB, concerning continuation, termination or other 
modifications of the study based on the observed beneficial or adverse effects of the 
treatment under study; 
7. Monitor the confidentiality of the study data and the results of monitoring; 
8. Assist the PI by commenting on any problems with study conduct, enrollment, sample 
size and/or data collection. 

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Sponsor-Investigator: Lee Fisher, PhD 
Version: 6/6/2023 
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4.4.1 Data Safety Monitoring Board Members 
The DSMB will include experts from a variety of relevant fields such as physical 
medicine & rehabilitation, neurology, and regulatory science/clinical trials. Members 
will consist of persons independent of the investigators who have no financial, scientific, 
or other conflict of interest with the study. Written documentation attesting to absence of 
conflict of interest will be required. The research monitor has the authority to stop the 
research at any time, can remove individuals from the study, and take any steps 
necessary to protect the safety and well-being of participants until the IRB has time to 
assess the study. Contact information for the DSMB Chairperson is included below. 
Dr. Ronald Glick, MD (Chairperson/Research Monitor) 
Center for Integrative Medicine, Suite 310,  
580 South Aiken Avenue, Pittsburgh, PA 15232 
4.5 Monitoring by study team 
The core members of this research team will meet at least monthly to discuss study 
recruitment, study goals and progress, adverse events, participant complaints, 
modifications, and confidentiality of ongoing studies. The investigators and study team 
will ensure that proper procedures are in place to ensure data integrity and participant 
safety. Data will be reviewed and any possible study design changes resulting from our 
experience or external studies/publications will be discussed. Our priority is to maintain 
participant safety and confidentiality while collecting data that accurately demonstrates 
the efficacy of this device. We will comply with the IRB's policy for the reporting of 
serious and unexpected adverse events as described in the Human Research Protection 
Office Policies and Procedures Manual. The outcomes of these meetings will be 
summarized and included in the annual continuing review. Minutes for these meetings 
will be kept on file. 
5.0 Labeling 
Labeling (Figure 2 and Appendix J) will be affixed to the outside of the Ripple Nomad and the 
outside of a plastic box that will house the Ripple stimulation front-ends (Section E, Sub-section 
2.4), passive circuitry to connect together up to five stimulation channels and connectors for the 
Abbott trial cables (Section E, Sub-section 2.3). A copy of the labeling for the device is included in 
Appendix J. 
 
Figure 2. Labeling for the SCS-LLA system, which will be affixed to the outside of the Nomad and the housing for the 
stimulation front-ends. 

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Sponsor-Investigator: Lee Fisher, PhD 
Version: 6/6/2023 
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6.0 Consent Materials 
Refer to Section L of this application. 
7.0 IRB Information 
University of Pittsburgh IRB & Human Research Protection Office (HRPO) 
Hieber Building, Main Office, Suite 106 
3500 Fifth Avenue, Pittsburgh, PA 15213 
Chair: Margaret Hsieh, MD 
8.0 Additional Records and Reports 
8.1 Data handling and record-keeping 
Case Report Forms (CRFs) will be completed for each subject enrolled into the clinical study. 
A full representation of CRFs are included in Appendix E. CRFs will be signed by the 
sponsor-investigator, a qualified sub-investigator, or a qualified member of the research team 
as indicated on each individual form. The sponsor-investigator will sign a Case Report 
Verification Form prior to lead placement and following lead removal to verify that they have 
reviewed all CRFs completed prior to the date of review. The sponsor-investigator’s signature 
serves as attestation of the sponsor-investigator’s responsibility for ensuring that all clinical 
and laboratory data entered on the CRF are complete, accurate and authentic. Any data that is 
missed will be noted with an explanation and investigator initials. Protocol deviations will be 
reported to the IRB as required. 
Source Data are the clinical findings and observations, laboratory and test data, and other 
information contained in Source Documents. Source Documents are the original records (and 
certified copies of original records); including, but not limited to, hospital medical records, 
physician or office charts, physician or nursing notes, subject diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, x-rays, etc. When 
applicable, information recorded on the CRF shall match the Source Data recorded on the 
Source Documents. Whenever possible, Source Data for clinical research procedures will be 
stored as a print out of the electronic medical record note. CRFs will be used to document the 
key outcome variables for each procedure and will also indicate that all original data was 
stored and backed up as appropriate. 
Paper-based records will be kept in a secure location in locked file cabinets within each testing 
institution facilities. All researchers involved with the conduct of this research have been 
appropriately trained in the proper practices of research conduct. Each subject will be assigned 
a unique subject identification code and the link to that code will be stored on a restricted 
research server (described below). Whenever feasible, identifiers will be removed from study-
related information and replaced by the subject identification code. 
We may share somatosensory research data to prevent the burden of repeat testing on 
individuals enrolled in our other neuroprosthetic studies in which somatosensory data is 
collected. This data will be coded. No clinical information will be shared. 

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Sponsor-Investigator: Lee Fisher, PhD 
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Photographing, videotaping, and/or voice-recording will be performed as part of this study and 
these data will be stored with study ID numbers in a locked office or on a password-protected 
research drive that can only be accessed by research staff.  
Electronic storage of research study information will be on a restricted access, separate server 
used only by research faculty and staff. In order to maximize data security as well as our ability 
to analyze the data efficiently, we will utilize two research servers: (1) University of Pittsburgh 
Medical Center (UPMC) and (2) Rehabilitation and Neural Engineering Laboratory (RNEL) on 
the University of Pittsburgh network. All identifiable information (excluding photographs, 
videotapes, and voice recordings) will be stored on the UPMC server. The UPMC server is 
managed by an information security group, which is comprised of three main areas: threat and 
vulnerability management, identity management and account administration, and the technical 
team. Protection of information is maintained in a variety of ways including firewall, 
individual password accounts, and identity management. 
Due to the large file size of the research data, we plan to store de-identified data locally on the 
RNEL laboratory server. This server is password protected and only research personnel 
affiliated with this project will be able to access study-related data. All original data will be 
stored in a ‘read only’ folder and will also be backed up at a separate location either on DVD in 
a locked file cabinet or on a separate password-protected backup server. The case report forms 
related to electronic data collection will also document that the data was stored and backed-up 
appropriately. All case report forms will be verified by the sponsor-investigator. Electronic 
systems used for data storage have not been certified as operating in full compliance with the 
FDA regulations at 21 CFR Part 11 due to the limited scope of this clinical investigation. 
Our study team will conduct regular reviews of ongoing data analysis to ensure the accuracy 
and validity of these methods. In no way will any of the original data be altered through these 
procedures. All case report forms, log sheets, and data and safety monitoring minutes will be 
made available to FDA or IRB representatives as requested. 
All data will be kept for a minimum of 7 years after the study ends in compliance with the 
University of Pittsburgh guidelines. Collaborating investigators may have access to study data 
after de-identification. 
8.2 Record maintenance and retention 
The sponsor-investigator will maintain records in accordance with Good Clinical Practice 
guidelines to include: 
o FDA correspondence related to the IDE application and Investigational Plan; 
including copies of submitted FDA Form 3500As, supplemental IDE applications, 
current investigator lists, progress reports, notice of device recall or disposition, and 
failure to obtain informed consent reports; 
o IRB correspondence (including approval notifications) related to the clinical protocol; 
including copies of adverse event reports and annual or interim reports; 
o Current and past versions of the IRB-approved clinical protocol and corresponding 
IRB-approved consent form(s) and, if applicable, subject recruitment advertisements. 
o Signed Investigator’s Agreements and Certifications of Financial Interests of Clinical 
Investigators; 

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Sponsor-Investigator: Lee Fisher, PhD 
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o Curriculum vitae (sponsor-investigator and clinical protocol sub-investigators); 
o Certificates of required training (e.g., human subject protections, Good Clinical 
Practice, etc.) for sponsor-investigator and listed sub-investigators; 
o Instructions for on-site preparation and handling of the investigational device and/or 
study treatment or diagnostic product(s), and other study-related materials (i.e., if not 
addressed in the clinical protocol); 
o Signed informed consent forms; 
o Completed Case Report Forms; signed and dated by sponsor-investigator; 
o Source Documents or certified copies of Source Documents; 
o Monitoring visit reports; 
o Copies of sponsor-investigator correspondence to sub-investigators, including 
notifications of adverse effect information; 
o Subject screening and enrollment logs; 
o Subject identification code list; 
o Investigational device accountability records, including documentation of device 
disposal; and the 
o Final clinical study report. 
Identifiable data will be filed in locked areas immediately after collection. Study ID numbers 
will be used instead of the participant’s name when recording study-related data. The 
information collected in this study, such as neural recordings, will generally consist of numbers 
with little or no meaning to the casual observer. Electronic data is stored on password-protected 
network drives. Staff has been trained regarding the critical nature of participants’ privacy, and 
about the procedures for respecting their privacy and maintaining confidentiality. Subject 
names and other directly identifiable information will not appear on any reports, publications 
or other disclosures of clinical study outcomes. 
The sponsor-investigator will retain the specified records and reports for up to 7 years after 
investigations under the IDE have been discontinued and the FDA so notified. 
 
 

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Sponsor-Investigator: Lee Fisher, PhD 
Version: 6/6/2023 
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