Spinal Cord Stimulation With Wire Leads to Restore Cough
Phase: NA
Conditions: Spinal Cord Injuries, Spinal Cord Diseases, Paralysis, Central Nervous System Diseases, Cough, Trauma, Nervous System, Wounds and Injuries
Sponsor: MetroHealth Medical Center

Spinal Cord Stimulation with Wire Leads to Restore Cough  
IRB #: IRB15-00014 
Date Approved: 4/10/2015 
_________________________________________________________________________________________________ 
 
 
 
 
Spinal Cord Stimulation with Wire Leads to Restore Cough 
IRB15-00014 
 
NCT number 01659541 
 
Date of the document: 11-23-2021 
Title of the document: Study Protocol  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Spinal Cord Stimulation with Wire Leads to Restore Cough  
IRB #: IRB15-00014 
Date Approved: 4/10/2015 
_________________________________________________________________________________________________ 
 
HUMAN INVESTIGATION PROTOCOL 
 
I. 
Investigators                 Anthony F. DiMarco, MD. 
Department of Physical Medicine & Rehabilitation 
Phone: (216) 778-3906 
 
Krzysztof E. Kowalski, PhD. 
Department of Physical Medicine & Rehabilitation 
Phone: (216) 778-88239 
 
Robert T. Geertman, MD. 
Department of Department of Neurosurgery 
Phone: (216) 778-8019 
 
Kutaiba Tabbaa, MD 
Department of Anesthesiology 
Phone: (216) 778-3700 
 
 
II. 
Title  
Spinal Cord Stimulation with Wire Leads to Restore Cough 
 
III. 
Key Words 
o spinal cord injury 
o paralysis 
o cough 
o cervical spinal cord injury 
o thoracic spinal cord injury 
 
IV. 
Abstract 
 
Respiratory complications account for significant morbidity and mortality in persons with spinal cord injury (SCI) 
due to their inability to cough and clear secretions. Consequently, they are dependent upon caregiver assistance 
for the application of manual suctioning, assisted coughing maneuvers or other methods of airway management. 
These methods are cumbersome, generally uncomfortable and require trained personnel. These individuals lack 
an effective cough mechanism due to paralysis of their expiratory muscles. Since the spinal cord below the level 
of injury is intact in most subjects, the motoneurons of the spinal cord and peripheral neuromuscular apparatus 
remain functional. Therefore, the expiratory muscles are amenable to functional electrical stimulation techniques. 
In a single site, pilot study of 16 tetraplegics, we have recently shown that the expiratory muscles can be 
electrically activated by spinal cord stimulation (SCS) to restore an effective cough, a method which involves the 
surgical placement of disc electrodes through laminotomy incisions. We demonstrated that this method is 
successful in achieving an effective means of expiratory muscle activation, as demonstrated by the generation of 
large positive airway pressures and expiratory airflow rates. Importantly, this technique facilitates secretion 
removal, reduces the need for caregiver support, reduces the incidence of respiratory tract infections and improves 
life quality. While successful, electrode placement requires an invasive and costly procedure. Consequently, many 
individuals were unwilling to pursue this technique. Based upon the results of animal and human studies, it is our 

Spinal Cord Stimulation with Wire Leads to Restore Cough  
IRB #: IRB15-00014 
Date Approved: 4/10/2015 
_________________________________________________________________________________________________ 
hypothesis that comparable activation of the expiratory muscles can be achieved with wire leads which can be 
inserted percutaneously through a needle, eliminating the need for the invasive laminotomy procedure and can be 
performed on an out-patient basis. This latter procedure would significantly shorten surgical time, lessen the 
degree of surgery, shorten recovery time, reduce costs, and thereby, increase patient and physician acceptance of 
this technique. The efficacy of SCS with wire leads will be assessed in 16 subjects with SCI, in terms of the 
capacity of this method to activate the expiratory muscles, restore an effective cough mechanism and achieve 
significant clinical benefits related to secretion management. Given the significant heterogeneity of this orphan 
population, subjects will serve as their own controls to evaluate the success of this technique. If successful, the 
wire lead system will provide a minimally invasive method of restoring cough and has the potential to 
significantly improve life quality. Ultimately, restoration of an effective cough with SCS has the potential to 
significantly improve the morbidity and mortality associated with respiratory complications in persons with SCI. 
This study will also provide the data necessary for a multi-center trial of this technique leading to eventual FDA 
approval. 
 
Primary Aims: 
 
1. Determine the utility of lower thoracic SCS with wire leads to produce large positive airway 
pressures and high peak expiratory airflow rates characteristic of an effective cough 
mechanism. 
 
2. Evaluate the capacity of this technique to provide an effective means of clearing airway 
secretions, reduce the need for caregiver support, reduce the incidence of respiratory tract 
infections and improve subject quality of life and caregiver burden in subjects with cervical 
SCI. 
 
Secondary Aims: 
 
1. Determine if the use of wire leads for restoration of cough has greater appeal to patients with 
SCI and is associated with less risk and cost compared to the current method of SCS to restore 
cough. 
 
2. Determine if the information from this study provides the necessary data to perform a multi-
center trial and obtain FDA approval of this device. 
 
V. 
Description and Rationale  
 
Problem. 
Respiratory complications still account for most of the morbidity and mortality in traumatic spinal cord injury 
(SCI) during the acute phase and also during later years. Despite intensive respiratory management, these patients 
frequently develop atelectasis, bronchitis and pneumonia. In epidemiological studies of over 5,000 patients 
sustaining SCI, the leading cause of death was pneumonia.3 In fact, patients with SCI are ~150 times more likely 
to die from pneumonia compared to the general population.17 The development of respiratory complications in 
SCI is directly related to the inability of these patients to cough and clear secretions. The lack of an adequate 
cough defense system occurs as a consequence of paralysis of virtually all of their expiratory muscles. Currently 
employed techniques to manage airway secretions include active suctioning, manual assistance by abdominal 
compression and/or use of a mechanical insufflation-exsufflation device. Each of these methods requires 
provider-patient coordination and is costly and labor intensive, requiring the constant presence of trained 
personnel. Moreover, despite use of these various modalities, respiratory complications continue to have a major 

Spinal Cord Stimulation with Wire Leads to Restore Cough  
IRB #: IRB15-00014 
Date Approved: 4/10/2015 
_________________________________________________________________________________________________ 
impact on the overall health and quality of life of patients with SCI.  Functional electrical stimulation of the 
expiratory muscles has the potential to provide a more normal and effective cough mechanism. 
 
Conventional techniques for airway clearance. 
There are several different methods of airway clearance of secretions currently employed in the management of 
spinal cord injured patients who do not have a functional cough. These include: A) Gravity. By this method, the 
patient is placed in the supine or prone posture with the head in a dependent position. The position of the body is 
rotated to allow secretions from different lobes of the lung to drain by gravitational effects alone. B) Active 
Suctioning. By this method secretions are cleared by inserting a catheter either through the nasopharynx or 
tracheostomy to suction the airways with the use of a mechanical pump. This method is generally successful for 
removal of heavy secretions from the large airways. C) Assisted Cough. This method involves the application of 
external force to the abdominal wall, usually by a therapist or assistant. The patient rests in a reclining position, 
and the abdominal wall is compressed forcefully to increase abdominal pressure and, consequently, intrathoracic 
pressure to expel secretions.  
 
Unfortunately, each of these methods has significant limitations which limit their effectiveness. The removal of 
secretions by gravity requires repositioning patients in relatively awkward positions for prolonged time periods 
and is quite uncomfortable. Active suctioning clears secretions from the large airways, but does not allow active 
removal of secretions from small airways where they are produced and often create problems with gas exchange. 
Furthermore, this method can result in tracheal injury and irritation causing recurrent hemoptysis and patient 
discomfort. The assisted cough method can increase intrathoracic airway pressures to a small extent (10-15%). 
However, unlike natural cough production, this method does not result in uniform distribution of pressure within 
the intrathoracic cavity and, therefore, has limited effectiveness in many patients. In addition, this method is labor 
intensive requiring the assistance of a therapist to position the patient and perform the maneuver.  
 
The deposition of material within the tracheobronchial tree occurs during various normal physical phenomena 
including inspiration, sedimentation, gas movement, turbulence and electrostatic forces. Most secretions are 
usually removed by mucociliary activity which washes the mucus blanket of the airways above the trachea, 
functioning as a mucociliary escalator. This mechanism is quickly overwhelmed when secretions become 
excessive; in which case, cough becomes the primary means of secretion removal. For patients with spinal cord 
injury who lack an effective cough, active suctioning is usually required to remove secretions on a regular basis, 
usually several times per day.  
 
Currently, therefore, there is no adequate method for achieving normal cough in this patient population. As a 
consequence, they suffer from the frequent development of respiratory complications, particularly respiratory 
tract infections. 
 
Innovation 
There are three potential methods by which the expiratory muscles can be activated to produce cough: 1) high-
frequency magnetic stimulation (MS), 2) surface abdominal muscle stimulation (SS) and 3) lower thoracic SCS. 
First, MS is an experimental device which can be applied to the lower back to activate the neural pathways 
innervating the expiratory muscles. While this technique has the important advantage that it can be applied non-
invasively, previous studies evaluating this technique in tetraplegic patients did not demonstrate significant 
increases in airway pressure generation. Moreover, this method has significant limitations including the 
generation of substantial heat at the stimulating coil and associated risk of thermal injury and lack of portability. 
With SS, substantial airway pressures can be generated with electrodes with very large surface areas.  However, 
as with MS, this method carries the risk of thermal injury, skin irritation and breakdown. Finally, we have 
previously shown that SCS using disc electrodes results in activation of the expiratory muscles and the generation 
of large positive airway pressures and high peak expiratory airflow rates, in the range of those observed during a 

Spinal Cord Stimulation with Wire Leads to Restore Cough  
IRB #: IRB15-00014 
Date Approved: 4/10/2015 
_________________________________________________________________________________________________ 
maximal cough effort in normal individuals. In contrast to MS and SS, this device is portable, does not require 
the repeated application of electrodes to the body surface, thereby avoiding potential skin injury, and is more 
likely to be effective in all patients, even obese individuals. Unfortunately, disc electrode placement requires a 
costly and invasive procedure significantly limiting general application. It should be emphasized that this 
technology is not commercially available. Wire leads have been in clinical use for several decades for control of 
pain and spasticity using a minimally invasive surgical procedure allowing for significant clinical advantages over 
disc electrodes. Based upon our extensive studies in animals and temporary, intra-operative placement of wire 
leads in humans, we have determined that SCS to restore cough can be accomplished with wire leads in a parallel 
arrangement. 
 
Specific aims and hypotheses 
 
The purpose of the study is to assess the utility of spinal cord stimulation to provide large positive airway 
pressures and expiratory airflow and simulate cough. Restoration of an effective cough in spinal cord injured 
(SCI) patients should reduce the incidence of atelectasis and respiratory tract infections and thereby reduce the 
high morbidity and mortality associated with respiratory complications in this patient population. 
 
Hypothesis, therefore, that spinal cord stimulation (SCS) with wire leads, which can be inserted via minimally 
invasive techniques can a) be applied safely without the development of neural injury, b) result in sufficient 
activation of the expiratory muscles in persons with SCI to produce an effective cough mechanism, and c) have a 
significant clinical impact related to secretion clearance on subjects with SCI. 
 
 
VI. 
Subject population 
 
Number and description of subjects  
We plan to evaluate 16 subjects of either sex. No subject will be excluded on the basis of race, religion or ethnic 
background. No pregnant women, children, prisoners, unconscious or incompetent people will be eligible. 
 
Source and method of recruitment 
Contact will be made via letter or phone call to potential research subjects made known to us through the 
assistance of the Spinal Cord Center at MetroHealth Medical Center, the General Clinical Research Center, and 
previously known subjects from other trials. 
 
Service responsible for medical care  
The physician currently responsible for each patient's care will continue to provide primary medical care. We 
plan to work closely with that physician in terms of the management of spinal cord stimulation. 
 
Inclusion and Exclusion Criteria 
 
Inclusion criteria: 
• Cervical spinal cord injury (C8 level of higher) 
• 12 months post-injury (if AIS incomplete) or 6 months post-injury (if AIS complete) 
• Expiratory muscle weakness (maximum expiratory pressure < or equal to 30% predicted normal 
value) 
• 18 - 75 years old 
• Determined by the surgical team to be an appropriate surgical candidate 

Spinal Cord Stimulation with Wire Leads to Restore Cough  
IRB #: IRB15-00014 
Date Approved: 4/10/2015 
_________________________________________________________________________________________________ 
• Adequate oxygenation (oxygen saturation > or equal to 90% on < or equal to 4 lpm supplemental 
oxygen) 
 
Exclusion criteria: 
• Untreated lung, cardiovascular or brain disease 
• Minor infection at the site of implantation requiring antibiotics within the past 3 weeks 
• Serious infection requiring hospitalization within the past 6 weeks 
• Severe scoliosis or other chest deformity 
• Marked obesity (body mass index > 50) 
• Unmanaged hypertension or hypotension 
• Low oxygenation (oxygen saturation < 90% on < or equal to 4 lpm supplemental oxygen) 
• Pregnant or breast feeding 
 
Special considerations for particular groups of subjects 
Prisoners, minors, legally incompetent or unconscious patients, pregnant women, housestaff, students and CWRU 
employees will not be studied. 
 
VII. 
Methods and procedures 
 
General study design 
 
Preliminary Assessment 
Prior to surgery, a history and physical examination will be completed. The following laboratory studies will be 
obtained: complete blood count with differential; comprehensive metabolic panel, which includes glucose, blood 
urea nitrogen, creatinine and calcium, total protein and albumin; prothrombin time, partial thromboplastin time 
and INR; and urinalysis with urine culture and sensitivity. A standard 12-lead electrocardiogram and chest x-ray 
will be obtained. MRI of the thoracic and lumbar spine and plain x-ray of the thoracic and lumbar spine may also 
be performed, unless contraindicated due to an existing condition. In the event an MRI cannot be performed, a 
CT myelogram is a suitable substitute. Significant abnormalities in any of these tests may interfere with the 
potential efficacy of SCS and, therefore, preclude surgery. Baseline spirometry will be measured utilizing 
standard equipment. Respiratory muscle strength will be assessed from measurements of maximal inspiratory 
pressure (MIP) and maximal expiratory pressure (MEP) using a digital meter. The best of 3-5 efforts will be used. 
Predicted normal values will be calculated using NHANES III 1999 for spirometry and Enright 1995 for maximal 
respiratory pressures. 
 
Surgical Procedures 
In the operating room at MetroHealth Medical Center, Dr. Tabbaa (staff anesthesiologist) and/or Dr. Geertman 
(staff neurosurgeon) will perform the implantation of the spinal cord wire leads (Ardiem, Inc; Indiana, PA) and 
radiofrequency receiver (Finetech Medical; London, England). A separate member of the anesthesiology team 
will be present to monitor hemodynamic and ventilatory status. Patients will receive moderate IV sedation, which 
is the clinical standard for the implantation of epidural wire leads. The subjects will be placed in the prone posture 
with a pillow placed beneath the hips, prepared and draped. Under fluoroscopic guidance, the L1-L2 interspace 
will be identified. One and one-half vertebral levels caudal and lateral to the midline, the skin will be infiltrated 
with lidocaine 1% with bicarbonate using a 25-gauge needle. An incision will be made to the depth of the 
subcutaneous fascia and a size 14-gauge Tuohy needle will be inserted into the epidural space until resistance is 
met. Needle location will be confirmed under fluoroscopy. After rotating the needle so that the beveled edge faces 
cephalad, the needle stylet will be removed. For the second wire lead, a second needle will be placed, following 
the same steps as above, at an equal distance from the midline but to the right of the midline and approximately 

Spinal Cord Stimulation with Wire Leads to Restore Cough  
IRB #: IRB15-00014 
Date Approved: 4/10/2015 
_________________________________________________________________________________________________ 
one vertebral space below the first needle. The guide wire will be inserted through the first needle and advanced 
1-3 cm past the needle tip. After removing the guide wire, the wire lead will be inserted through the needle, under 
fluoroscopic guidance, and advanced until the superior electrode contact is positioned at the T9 level just left of 
the midline. The second lead wire will be then be inserted to the right of midline, following the same steps just 
described, and advanced to the T9 spinal level. After verifying lead position using fluoroscopy, the needles will 
then be removed. Each wire lead will be secured with an anchor. A separate ground electrode will be implanted 
in a pocket over the paraspinal muscles. The lead wires will be tunneled to the mid-axillary area. The lead incision 
sites are then closed. The subject will then be placed in the lateral decubitus position and an incision will be made 
over the abdomen or lower chest to make a subcutaneous pocket. The radiofrequency receiver, identical to the 
receiver used in our recent clinical trial, will be placed in the pocket. Each lead wire will be connected via a 
connector receptacle to the receiver. The fascia and the subcutaneous tissue are then closed.  In this protocol, the 
entire system will be implanted during a single procedure. SCS will be applied to each lead intra-operatively to 
verify electrode position. As with any surgical procedure, the subject will then be observed in the Recovery Room 
and, when stable from a hemodynamic and respiratory standpoint, admitted to a general medical ward (or 
telemetry unit for subjects with sleep apnea). Routine post-operative surgical care will be provided. The subject 
will be monitored for any signs of bleeding or infection. The subject is expected to be discharged the next day. 
 
The potential complications of this procedure include infection and bleeding. The incidence of each of these is 
generally considered to be less than 1%. Dr. Tabbaa has performed parallel wire lead placement routinely for 
other indications of SCS for more than 20 years. 
 
Postsurgical assessment 
Participants who live outside of the Cleveland area will be required to stay in Cleveland for 10 to 14 days after 
discharge for a postsurgical assessment at the MHMC by Dr. Robert Geertman or a member of his team. This 
required stay could be extended if deemed necessary by Dr. Geertman or his surgical team for an unknown period 
of time. 
 
Specific Physiologic Measurements  
Airway pressure and peak expiratory airflow rate measurements during hospital out-patient visits. 
Approximately 3-4 weeks after implantation of the SCS system, all subjects will return to the hospital for the 
initial application of electrical stimulation on an outpatient basis. At this time, cardiac rate and rhythm, oxygen 
saturation, and blood pressure will be monitored. All measurements will be made in the sitting posture. Airway 
pressure and peak expiratory airflow rate will be measured (connection will be made either with a facemask or 
tracheostomy tube), with a Biopac Data Acquisition System (Biopac Systems MP100). 
- Airway pressure.  Changes in airway pressure during expiratory efforts are reflective of the pressure developed 
within the major airways and will be used as an index of the force of expiratory muscle contraction. Prior to SCS, 
the subject will be asked to relax completely to assure absence of respiratory muscle activation. SCS will be 
applied for 0.6-0.8s during which time airway pressure will be recorded during airway occlusion.  
- Expiratory airflow rate. Peak expiratory airflow rate is also a useful index of cough efficacy and will be 
monitored in each subject. Inspired and expired volume will be obtained by integration of the airflow signal.  Peak 
expiratory airflow rate will be measured during SCS following release of occlusion. 
- Effects of lung volume changes.  Airway pressure generation will be assessed at both FRC and TLC. SCS will 
be applied at each of these lung volumes while measurements of airway pressure and peak expiratory airflow 
rates are made by the methods described above.  
Measurements will also be made with the subject making their own expiratory effort in synchrony with activation 
of the expiratory muscles by the stimulation system. The subject will be asked to exhale forcefully against an 
occluded airway in synchrony with muscle activation during which time airway pressure and peak expiratory 
airflow rate will be monitored. This is the prescribed pattern of use of the system at home by the subject in order 
to cough and clear their airways. 

Spinal Cord Stimulation with Wire Leads to Restore Cough  
IRB #: IRB15-00014 
Date Approved: 4/10/2015 
_________________________________________________________________________________________________ 
 
Assessment of Clinical Outcome Parameters 
The incidence of acute respiratory tract infections over a 2-year period will be collected prior to implantation of 
the study device. Following implantation, this will be tracked continually. Responses to questionnaires (life 
quality, caregiver burden and secretion management index) will be compared prior to implantation and also at 
defined endpoints during the study. Mean changes of each parameter for the entire group will be determined. 
 
Method of data analysis 
Graphs will be constructed relating changes in stimulus amplitude to airway pressure generation and expiratory 
airflow. Each of the subjects will serve as their own control. Upon overall significance, appropriate pairwise 
comparisons will be performed. Since these contrasts are equivalent to multiple t-tests between levels, protection 
against type I error will be accomplished with a Bonferroni correction. A p value of < 0.05 will be taken as 
indicating statistical significance. Statistical significance, however, does not necessarily translate into clinical 
significance. 
 
 
VIII. 
Safety of subjects and risk benefit status 
 
Potential risks 
 
1. Pre-surgical Risks 
Standard procedures will be performed prior to implantation of the investigational device to assure that the subject 
is appropriate for enrollment in the study and able to tolerate the surgical procedures. No experimental procedures 
will be performed during this period. Standard blood draws will be made for laboratory analysis. When blood is 
drawn from a vein, there will be some temporary discomfort and the minimal risk of local bruising, infection or 
blockage of the vein. Rarely, fainting occurs. Risks associated with radiation exposure may be related to the 
cumulative number of CT scans and other types of X-rays over a long period. Because the MRI machine functions 
as a large magnet, it could move iron-containing objects in the MRI room during the examination that could cause 
harm. Having a MRI may also cause some discomfort including claustrophobia and noise. 
 
2. Surgical Risks 
The surgical procedures will be performed by Dr. Tabbaa, staff physician in the Department of Anesthesiology 
and/or Dr. Geertman, staff physician in the Department of Neurosciences, both at MetroHealth Medical Center. 
Dr. Tabbaa has performed parallel wire lead placement routinely for other indications of SCS for more than 20 
years. Dr. Geertman has implanted the study device in all 17 of our participants in our previous clinical trial using 
disc electrodes. All aspects of the surgical procedure are standard. However, the application of the wire leads for 
the purpose of expiratory muscle stimulation is experimental. The surgical procedures are expected to last 2 hours. 
Any surgical procedure carries a risk of infection and bleeding. The incidence of infection and excessive blood 
loss related to this surgery are generally considered to be less than 1%. Although unlikely, there is also a chance 
that the body will reject the implanted materials which will require their removal. It is possible to develop a pocket 
of fluid (seroma) around the receiver, and, if infected, the receiver will have to be removed. There is also a rare 
possibility that the stitches holding the leads and receiver in place will break causing these to shift in position. 
Other potential risks include lead migration and leakage of cerebrospinal fluid. 
 
3. Risks Associated with Spinal Cord Stimulation 
Tetraplegic patients are known to suffer from a condition known as autonomic dysreflexia, a condition 
characterized by symptoms of headache, blotchy skin and sweating, high blood pressure and bradycardia. These 
symptoms can be triggered by SCS. In our recent clinical trial, these symptoms occurred in ~ 20% of subjects and 
subsided quickly with discontinuation of stimulation. There is a remote possibility that bowel or bladder discharge 

Spinal Cord Stimulation with Wire Leads to Restore Cough  
IRB #: IRB15-00014 
Date Approved: 4/10/2015 
_________________________________________________________________________________________________ 
will occur due to contraction of the abdominal muscles during stimulation. Of note, there has been no occurrence 
of this potential complication in our recent clinical trial using disc electrodes for SCS. Some leg movement may 
occur with T11 stimulation. In our recent clinical trial, this was well tolerated in each subject. Due to improper 
use of the external transmitter (i.e. maintained in place continuously for days and weeks with tight fitting 
clothing), the receiver may erode through the skin exposing the subject to the risk of infection.  There is the remote 
possibility of electrically induced tissue damage. This is unlikely since the ranges of stimulus amplitude and pulse 
width are known to be safe. Moreover, the duration of stimulation is very brief. It is possible that placement of 
the device may worsen spasticity after implantation. This is rare and may ultimately require removal of the device. 
Temporary or transient sensory changes, such as electric like sensations, may be present during stimulation. These 
are uncommon and well tolerated, but can be lessened with changes in the stimulation parameters. 
 
4. Device Malfunction 
The most common cause of device malfunction is decoupling of the external transmitter over the implanted 
receiver. Low battery power can also result in device malfunction. An error on the control box will display if 
there is low battery power. The battery charge status can be checked at any time on the control box. The 
occurrence of fibrosis at the electrode-tissue interface could affect the long-term physiologic performance of the 
device. These damages were not encountered in our recent clinical trial nor highly anticipated since the implanted 
materials are biologically inert. 
Improper activation of the implanted receiver could occur by external sources other than the subject’s transmitter. 
However, this is unlikely since the external transmitter must be placed close to the implanted receiver to power 
the device. 
 
Precautions to minimize risks 
1. Pre-Surgical 
During standard blood draws, suitable precautions will be taken to minimize risks of bruising, infection or 
blockage of the vein. 
Because MRI could result in movement of iron-containing objects, precautions will be taken to minimize such 
events. Loose metal objects, like pocketknives or key chains, will not be allowed in the MRI room. Earplugs will 
be applied to prevent temporary hearing loss. 
 
2. Surgical 
While the incidence of infection and excessive blood loss related to this surgery are generally considered to be 
very low, every effort to minimize this risk will be taken before, during, and after the procedure, including 
administration of antibiotics. 
 
3. Spinal Cord Stimulation 
Given the possibility of autonomic dysreflexia in response to SCS, blood pressure and pulse will be monitored 
closely during hospital out-patient visits and at home during the initial period of SCS. If significant blood pressure 
changes occur (systolic > 140 mmHg) during SCS or if the subject experiences symptoms of autonomic 
dysreflexia (AD), stimulation will be stopped until hemodynamic parameters stabilize. Based upon our previous 
experience, increasing the interval between applied SCS minimizes hemodynamic changes and when signs of AD 
occur initially, they eventually resolve completely over the subsequent 3-4 weeks such that stimulation can be 
provided very frequently without untoward effects. However, if signs or symptoms of AD persist, Clinical 
Practice Guidelines of the Consortium for Spinal Cord Medicine for management of AD will be followed. If 
necessary, the study will be discontinued. 
Given the potential of erosion of the receiver through the skin, the subject’s skin will be inspected daily for redness 
and/or irritation and any abnormalities immediately reported to the study team. The subject and caregiver will be 
instructed to remove the external transmitter each night, inspect the skin and immediately report any abnormal 
findings to the study team. 

Spinal Cord Stimulation with Wire Leads to Restore Cough  
IRB #: IRB15-00014 
Date Approved: 4/10/2015 
_________________________________________________________________________________________________ 
 
4. Device Malfunction 
To prevent decoupling of the external transmitter over the implanted receiver, the subject and caregiver will be 
provided specific instructions on proper application of the device. Methods to assure maintenance of adequate 
battery power will also be provided, including instruction on how to check the status of battery charge. The level 
of applied electrical stimulation will be maintained within specific parameters that are known to be safe and not 
result in deleterious side effects. 
 
Toxic/hazardous substances 
Not applicable 
 
Radiobiolical information 
Not applicable 
 
Potential benefits 
Based upon our recent clinical trial, lower thoracic spinal cord stimulation using disc electrodes results in near 
maximal expiratory muscle activation, as reflected by the generation of large airway pressures and expiratory 
airflow rates in the range of those achieved with a maximum cough effort in normal persons. More importantly, 
this technique is a highly effective method of secretion clearance as it significantly reduces the difficulty in raising 
secretions and the need for caregiver support, reduces the incidence of respiratory tract infections and improves 
life quality. Subjects also reported that this method is far more portable and comfortable compared to previously 
used methods of secretion management. 
 
It is our hypothesis that an effective cough can be achieved with SCS using wire leads, which can be placed by a 
much less invasive surgical procedure. If successful, this technique will have greater appeal to persons with SCI 
and be associated with less risk and cost while achieving the same clinical benefits. Moreover, this technique has 
the potential to reduce the high morbidity and mortality associated with respiratory complications in this 
population. 
 
 
IX. 
Significance 
 
Many spinal cord injured patients suffer from recurrent atelectasis, respiratory tract infections, including 
bronchitis and pneumonia and significant discomfort due to the inability to clear respiratory secretions and foreign 
bodies. Since conventional methods to remove secretions are tedious, labor intensive and oftentimes largely 
ineffective, respiratory complications remain a major cause of morbidity and mortality in this patient population. 
 
Lower thoracic SCS may provide a means of generating large airway positive pressures and expiratory airflows 
sufficient to mimic a normal cough. Restoration of cough may help reduce the incidence of respiratory 
complications and possibly improve both the life quality and longevity of spinal cord injured patients. 
 
 
X. 
Informed consent 
 
The protocol will be explained to each patient by one of the investigators with the informed consent form 
provided. The patient will sign the consent form if he or she agrees to participate in the study with full 
understanding of the purpose, risks and benefits of this research.