Effect of Single Session Combined Acute Intermittent Hypercapnic-Hypoxia and Transcutaneous Spinal Stimulation on Cervical Neural Drive in Chronic Spinal Cord Injury
Phase: NA
Conditions: Cervical Spinal Cord Injury
Sponsor: Thomas Jefferson University

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
Page 1 of 17 
 
 
 
1 
Jefferson Office of Human Research 
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Informed Consent OHR-8 
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Version Date – FOR OHR USE: 12/7/21 
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5 
Department: Center for Neurorestoration 
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Principal Investigators: Jayakrishnan Nair, PT, MSPT, PhD, Mijail Serruya, 
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MD, PhD 
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Study Title: Motor Restoration in Chronic SCI with Combinatorial 
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Intermittent 
Hypercapnic-Hypoxia 
and 
Transcutaneous 
Spinal 
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Stimulation 
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Lay Title: 
Combination Therapy with Therapeutic Air Mixture and 
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Electrical Stimulation on the Neck 
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General Information Section 
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Informed Consent 
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You are being asked to take part in a research study. Research is different 
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from standard medical care, and is done to learn something new. 
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Please read on to find out: 
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• The purpose of this research. 
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• How this research is different from standard medical care. 
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• The procedures involved. 
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• The risks. 
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• The possible benefits. 
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• The alternatives to taking part in this research. 
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You will have the opportunity to discuss this study with the research 
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personnel. Use this information to decide if you want to take part in this 
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research. This process is called informed consent. 
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37 
Voluntary Participation 
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You do not have to take part in this research. It is your choice whether or not 
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you want to take part. If you choose not to take part or choose to stop taking 
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part at any time, there will be no penalty or loss of benefits that you would 
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normally get. 
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PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
Page 2 of 17 
 
 
 
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Purpose 
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You are being asked to participate in this research study because you have 
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complete or partial paralysis due to a spinal cord injury (SCI). Paralysis 
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means that you are unable to move your arms, legs, hands or feet or you 
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have reduced use of them. The therapeutic air mixture and the study devices 
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may help with loss of strength, function or with complications of paralysis, 
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but there is not a guarantee that being in this study will help you. 
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The goal of this study is to evaluate if short bouts of breathing low oxygen with 
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elevated carbon-dioxide separated by breathing normal air combined with 
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non-invasive electrical spinal c o r d  stimulation c a n  help people with SCI  
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to improve strength and function of muscles involved in breathing and hand  
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function. The technical  name  of  this  breathing  approach  is  called  “acute   
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intermittent hypercapnic-hypoxia” or AIHH. 
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The study will involve five (5) visits. Each session will last up to four hours.  
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Each session will be scheduled on a separate day, with at least one week in  
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between, hence over a minimum of four weeks. Sessions involving   
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exposure  to therapeutic air (AIHH) followed by a short 20-30 min rest break.  
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After the rest break you will be asked to wear a noninvasive spinal electrical  
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stimulation device and perform occupational and/or physical therapy with  
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the spinal stimulator turned on. 
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Breathing the therapeutic air (AIHH) has previously been shown to improve 
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breathing health and hand strength. This appears to happen because it causes 
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nerve cells to build stronger connections with each other. This approach might 
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help people who have respiratory and hand weakness. The electrical energy is 
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delivered through surface electrodes placed on the skin, and is thought to 
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enable the spinal cord and nerves to become active again. Studies in animals 
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and humans suggest that improvements in hand and/or arm function and  
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other types of functional recovery might occur with AIHH as well as  
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electrical stimulation. 
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How this Research is Different from Standard Medical Care 
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This study will not include any standard of care procedures. This study is novel 
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because it combines two experimental therapies i.e. AIHH and non invasive 
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spinal electrical stimulation for improvement of function in muscles involved 
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in breathing and hand function. This study will also explore why some 
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individuals respond well and some do not. 
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As a part of this study, you will receive Physical therapy/Occupational therapy 
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exercise based intervention which is standard of care for patients with SCI. In 
87 
addition, you will receive an experimental gas mixture followed by electrical 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
Page 3 of 17 
 
 
 
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stimulation on the neck. Both of these interventions are not part of standard 
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of care. The novel non-invasive spinal electrical stimulation used in this study 
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may feel similar to transcutaneous nerve stimulation (TENS) and functional 
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electrical stimulation (FES) that are routinely performed as standard of care 
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for SCI in Physical therapy. Unique to this study, you may undergo up to a 
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maximum of two blood tests and one-time saliva collection 
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95    Number of Participants 
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97 
In total, 29 participants will be recruited in this part of the study. 
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Duration 
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This study involves a minimum of 5 separate visits to the laboratory. The first 
102 
visit will be screening, where the study physician will assess your safety and 
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Physical/Occupational therapist will determine if you meet the inclusion 
104 
criteria, followed by mapping of muscle response to magnetic and electrical  
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stimulation of your brain and nerves. Once you qualify for the study, you will be  
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asked to visit the laboratory on a minimum of 4 separate testing days, inter- 
107 
spaced with a minimum of 1 week washout period. Testing on all 4 sessions  
108 
will last for up to 4 hours. The total expected time requirement, therefore, is  
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approximately 16 hours, following the screening visit. If a testing session is  
110 
delayed due to equipment malfunction or other unexpected delays, testing  
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may take longer. If such a delay were to occur, you may be asked to either  
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stay longer than 4 hours (up to a maximum of 5 hours), and/or you may be  
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asked to return for an additional session beyond the original 4 (up to 6  
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sessions). 
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Procedures and Risks 
118 
It is important that you know the procedures and risks involved in this research. 
119 
These will be discussed with you and are included in detail later in this form. 
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Review the information carefully when making your decision to take part in 
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this research. 
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121 
Possible Benefits 
122 
123 
You may or may not personally benefit from taking part in this research. 
124 
Benefits may include helping improve paralysis and some conditions related 
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to paralysis. In addition, it may improve your function. Your state of paralysis 
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might not get better while you are in this study. Information from this study 
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might help researchers to better understand how to treat paralysis. 
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PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
Page 4 of 17 
 
 
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Alternatives to Taking Part in this Research 
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You have other options than taking part in this study. Participating in physical 
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and/or occupational  
133 
therapy with or without functional electrical stimulation is an alternative way 
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to continue to work toward making functional progress after your spinal cord 
135 
injury. The alternative to being in this study is to not take part. You may discuss 
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alternatives to participating in this research with study 
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staff or with your regular health care provider. 
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Costs 
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There will be no study related cost to you. If you receive a bill that you think is incorrect, 
142 
please contact the research personnel. There is no plan to pay you for lost wages, lost time from 
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work, personal discomfort, or for injuries or problems related to your underlying medical condition. 
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As stated in the next section on Payment, you will be paid for attending sessions. You may use that 
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Payment to pay for travel and parking if you wish. 
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Payment 
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150 
All participants are expected to be within the local Philadelphia area; therefore no hotel or airfare 
151 
reimbursement will be permitted. The estimated travel costs are as follows: 
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Participants will be reimbursed up to $50 for each test visit and $25 for screening visit. 
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Mileage reimbursement will be at the government 2022 rate of $0.56 per mile. 
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Parking will be reimbursed and may require the use of a TJU voucher. 
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The maximum amount of parking-and-travel cost per person will be $50 per visit. 
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All payments from Jefferson will be in the form of a ClinCard, a kind of debit card that you can 
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use to pay for any type of product or service just as you would use a regular debit or gift card. 
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Ending Study Early 
160 
161 
There are a number of reasons you may decide or be asked to stop the study 
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early (example: medical issues).  You may also have to stop the study early 
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even if you do not want to. You and the research personnel will discuss the 
164 
reason if this becomes necessary. If you do leave the study early, you may be 
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asked to complete some of the procedures described in this form. 
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167 
New Information 
168 
169 
New information may come out during this study.  You will be given any new 
170 
information that could change your decision to take part.  You may ask to see 
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the information collected about you, but not until the entire study is complete. 
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You will be given any research results that could affect your health. 
173 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
Page 5 of 17 
 
 
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Detailed Information Section 
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Procedures 
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While you are in this study, you will undergo different procedures which  
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are described below. Please note that additional tests and procedures may  
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be needed to check on your health condition. 
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This study consists of four (4) intervention visits and one (1) baseline  
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assessment visit, with at least 1 week interval between sessions. During  
184 
sessions, you will be asked basic questions about you and your health and  
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then undergo exposure to therapeutic air mixture (AIHH), non- 
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invasive electrical stimulation, and functional testing. In addition, up to 10 ml 
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blood will be drawn at the beginning of combinatorial treatment session and 
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saliva sample will be collected once.  
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1. Box & Blocks and Pinch and Grip Force Assessments: These functional tests  
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   will measure your strength and ability to use your upper extremity and 
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   hand. 
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2. Maximum inspiratory pressure: You will be asked to exhale  
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   completely and attempt a maximal inhalation through a mouthpiece for at  
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   least 2 seconds against resistance. The mouthpiece connected to a pressure  
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   transducer will record the amount of force you can generate to inspire air. 
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3. Mouth occlusion pressure: This measure will be obtained while you 
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breathe through a mouthpiece connected to a 2-way valve in a closed 
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circuit. The  valve  through  which  you  will  be  inhaling  air  will  be 
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momentarily occluded without your awareness, after you have expired air, 
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until the next breath. 
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4. Magnetic stimulation (cervical, CMS and transcranial, TMS) and electrical  
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nerve conduction study: CMS, TMS, and electrical nerve conduction  
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studies are safe and non-invasive nerve stimulation techniques that  
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have been used in clinical and research settings for over 30 years. We  
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will perform a series of magnetic stimulations on top of your head 
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(known as transcranial magnetic stimulation) and over the back of your 
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neck (known as cervical magnetic stimulation) or in your forearm and  
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hand in order to activate the phrenic nerve that innervates the  
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diaphragm and/or hand muscles. These procedures are commonly  
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used in research and are well-established. During these stimulations,  
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we will record electrical activity of the diaphragm muscle using  
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surface electrodes placed on the chest wall over your ribs. We will  
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then record your resting breathing and monitor cardiovascular variables  
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like heart rate and blood pressure. You will then breathe a  
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predetermined gas concentration for approximately 30 minutes while we  
217 
record breathing and cardiovascular responses. We will continue to  

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
Page 6 of 17 
 
 
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monitor these readings for up to 1 hour after exposure. We will then  
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perform a final set of magnetic stimulations to compare with baseline. 
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5. Surface electromyography (EMG): EMG will be conducted to record the 
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activation of breathing muscles during the respiratory tests. By analyzing 
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the electrical activity generated during a muscle contraction, EMG 
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analyses  allow  us  to  understand  timing  and  amplitude  of  muscle 
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activation as well as the frequency content of the EMG signal. Using a 
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standard surface preparation (cleaning the skin with water or alcohol pad, 
225 
shaving of excess hair) and electrode placement, EMGs will be collected 
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from your muscles involved in inspiring air using surface EMG electrodes. 
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EMG sensors will be attached to the skin with hypoallergenic medical 
228 
tape. Before data is collected we will check to ensure that the quality of 
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EMG signal is free from noise and interference. The electrode gel used 
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during electrode placement is slightly abrasive and may cause skin 
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irritation. We encourage you to inform the researcher of any skin 
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conditions and discomfort during electrode placement. 
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6. RT Xcite device: This device uses electrical stimulation, which is a form 
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of electrical energy that passes through your skin and the tissue below 
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your skin, such as your fat and muscles, down to the nerves and nerve 
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cells that make up your spinal cord. The type of electrical energy being 
237 
used is thought to enable the spinal cord and nerves to become active 
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again after an injury or illness which has caused paralysis. Studies in 
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animals and humans suggest that improvements in hand and/or arm  
240 
function and other types of functional recovery might occur with this  
241 
type of stimulation. The device uses gel electrodes that are placed on  
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your skin. These electrodes will be placed on specific locations on the  
243 
skin of your neck a n d / or back and will be connected to a  
244 
stimulator. The electrodes have a hydrogel sticky surface; so if you  
245 
have an allergy to any type of gel or adhesive material, please inform the  
246 
study staff. 
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7. Respiratory resistance training: This intervention will involve using a 
248 
special  mouthpiece  to  provide  resistance  when  you  are  inspiring 
249 
(breathing in) or expiring (breathing out) air from the room around you. 
250 
You will be asked to breathe against resistance that will be based on your 
251 
own individual respiratory strength (determined prior to starting the 
252 
intervention). You will be asked to complete three training sets of 
253 
approximately 6-12 repetitions of breathing in and three training sets  
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of approximately 6-12 repetitions of breathing out. You will be given short  
255 
rest periods of about 10-15 seconds of normal breathing between  
256 
repetitions. We will monitor your heart rate and blood pressure at regular  
257 
intervals. You may take longer rest periods if needed. 
258 
8. Functional strength training: you may be asked to perform motions  
259 
Of different parts of your body, to the best of your ability. This practice  
260 
will be familiar to you, as it will be exactly what is done in traditional,  

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
Page 7 of 17 
 
 
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standard-of-care occupational and physical therapy; and it will be  
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performed with a certified occupational or physical therapist. You will 
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be given rest periods following the same guidelines that therapists  
264 
typically use in outpatient rehabilitation. We will monitor your heart rate  
265 
and blood pressure at regular intervals. You may take longer rest  
266 
periods if necessary.  
267 
9. Blood Draws: Following completion of the initial paperwork, you will be 
268 
asked for a blood draw. A registered nurse/phlebotomist will collect 10 ml 
269 
of blood which is roughly equal to 2 teaspoons. The blood sample will be  
270 
   collected from your arm by inserting a small needle. Your blood will be  
271 
   drawn only once, which is during the first intervention session. It will be 
272 
   stored in a secured location with your coded study ID until the end of the   
273 
   study. After the study is over the sample will be destroyed and discarded. 
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10.Saliva Collection: At one time point during your five research  
275 
visits, you will be asked to submit 2ml of saliva by spitting into a  
276 
sterile container. The collected saliva will be processed and analyzed to  
277 
determine if you respond or not to treatment based on your individual  
278 
genetic differences. The saliva will be collected only once and stored in  
279 
a secured location with your coded study ID until the end of the study.  
280 
After the study is over the sample will be destroyed and discarded. 
281 
 
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11.Blinding: Participants and blinded assessors will be made aware of 
283 
possible air mixtures, but not made aware of the intervention delivered. 
284 
Based upon reports from participants (N=6) blinded during prior study 
285 
(Hayes et al., 2014), 4 of 6 guessed incorrectly or were uncertain of the 
286 
Acute Intermittent Hypoxia (AIH) intervention received, suggesting our 
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prior blinding and air delivery methods were effective; 
similar 
288 
uncertainty was reported in all published trials in humans with SCI. 
289 
However, participants receiving AIHH intervention with elevated CO2 
290 
pressure are likely to experience mild levels of dyspnea/ air hunger and 
291 
are therefore more likely to correctly guess the intervention. Regardless, 
292 
we will rigorously monitor and quantify blinding integrity by asking 
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blinded participants and assessors to guess the intervention received at 
294 
the end of each intervention and to indicate guess confidence using a 
295 
Likert  scale  (Likert,  1932;  Brunoni  et  al.,  2014).  We  will  use  a 
296 
contingency table and Fischer’s Exact Test to determine if the 
296 
         probability of correct guessing is different from chance. 
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Risks 
300 
Taking part in this study involves certain risks. There may also be risks that 
301 
are not known at this time. If you have any medical issues during this study, 
302 
call the appropriate number in the contacts section of this form. 
 
 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
Page 8 of 17 
 
 
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AIHH and Respiratory and Hand Muscle Strength training: The risks associated  
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with AIHH and respiratory strength training are minimal and the lower  
305 
oxygen levels associated with AIHH have been shown to be easily tolerated  
306 
without discomfort or negative responses. Specifically, many studies have  
307 
shown that AIHH at the levels and dosage used in this study, and respiratory  
308 
or hand muscle strength training can be delivered safely, with no adverse  
309 
events. 
Furthermore, we will work to ensure your safety and comfort throughout all of 
311 
the study procedures. We will ask you questions regularly to monitor your 
312 
general health, such as questions about your pain, spasticity, medication-use, 
313 
or sleep. You will be asked to let us know if you have any dizziness, headache, 
314 
vision changes, or any other feeling of discomfort throughout the study. We 
315 
encourage you to let the study staff know about your comfort and how you are 
316 
feeling throughout all study procedures to ensure your safety and comfort. 
317 
A licensed clinician with experience working with individuals with spinal cord 
318 
injuries will oversee all participant testing and interventions. You will complete 
319 
the study procedures while seated or lying down in a safe and supported 
320 
manner and your responses to testing and interventions will be observed 
321 
closely. 
Additionally, you will be allowed to take rest breaks as often as 
322 
needed. 
323 
324 
Common discomforts that may occur in this study and steps to alleviate them 
325 
are: 
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1) The mask used to deliver the low and higher level oxygen mixtures may be 
327 
uncomfortable. The fit and placement of the mask will be adjusted as 
328 
necessary to ensure maximum comfort. Additionally, the mask will be removed 
329 
during periods of breathing normal room air to give you a break from wearing 
330 
the mask. 
331 
2) You may feel sleepy during delivery of either gas mixture. This may be due 
332 
to breathing low-oxygen air, or due to sitting still in a reclined position. Feelings 
333 
of sleepiness typically last only for the duration of the intervention. Both gas 
334 
mixtures will be delivered while you are seated in a semi-reclined position with 
335 
head, arm, and feet support as necessary for comfort, and to ensure safety. 
336 
Additionally, study staff will talk with you throughout the interventions to keep 
337 
you engaged and encourage you to stay awake. 
338 
3) You may feel slight discomfort and/or fatigue during or shortly after bouts 
339 
of respiratory strength training due to the effort involved in completing the 
340 
training. You will be provided as much rest as necessary in between sets of 
341 
training exercises to lessen any fatigue. Heart rate, blood oxygen saturation, 
342 
and blood pressure will be continuously monitored throughout respiratory 
343 
strength training to ensure that you are not over-exerting yourself during the 
344 
training. 
 
 
 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
Page 9 of 17 
 
 
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Rare but possible risks in this study and steps to alleviate them are: 
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1) 
Breathing low levels of oxygen and slightly elevated carbon-dioxide 
347 
(during AIHH) causes low levels of oxygen and high levels of carbon-dioxide in 
348 
the blood. Side effects of low blood oxygen levels can include lightheaded 
349 
sensations, dizziness, reduced vision, or euphoria. If you report any of these, 
350 
or other general discomfort during the low-oxygen intervals, delivery of AIHH 
351 
will be terminated. The effects of breathing intermittent low levels of oxygen 
352 
are well-studied in humans and methods proposed here are deemed safe. Our  
353 
mild AIHH dose is based on human studies that delivered AIHH without 
354 
unwanted side effects. 
355 
2) Significant sudden increases or decreases in heart rate, respiratory rate, 
356 
or blood pressure may be signs of an adverse response to study procedures. 
357 
To minimize risks from sudden increases or decreases in heart rate, respiratory 
358 
rate, or blood pressure, these vital signs will be monitored throughout all study 
359 
procedures. In the event that one or more of them shows a sudden change, 
360 
study procedures will be stopped. Your vitals will be monitored by study staff. 
361 
If you report additional discomfort or the vitals do not return to baseline in a 
362 
time deemed safe by study staff, the study physician and principal investigator 
363 
will be notified and/or, if necessary, emergency medical services will be 
364 
contacted. 
365 
3) 
Reproductive risks--Because the treatment in this study might affect an 
366 
unborn baby, you should not become pregnant while in this study. Since this 
367 
treatment will not be given to any patients who are pregnant, all women of 
368 
childbearing potential must take a pregnancy test prior to receiving any 
369 
treatment on this study. We encourage all women enrolled on this study to 
370 
use one of the effective birth control methods while enrolled in this study. 
371 
These methods include total abstinence (no sexual intercourse), oral 
372 
contraceptives ("the pill"), an intrauterine device (IUD), an etonogestrel 
373 
implant (Implanon), or medroxyprogesterone acetate injections (Depo-Provera 
374 
shots). If one of these cannot be used, using contraceptive foam and a condom 
375 
are recommended. 
You must notify the study staff if you become pregnant 
376 
during the course of the study. 
377 
4) During muscle activity recording (surface electromyography) adhesive 
378 
from the disposable stickers might be uncomfortable when peeled off hairy 
379 
skin. Hair may be shaved from the skin prior to placement of electrodes to 
380 
avoid discomfort when removing. 
381 
382 
Risks  associated  with  noninvasive  spinal  cord  stimulation:  Skin  surface 
383 
electrical stimulation via hydrogel electrodes is known to commonly cause 
384 
minor discomfort during or after stimulation. Skin irritation or redness from the 
385 
electrodes. Muscle or joint stiffness, discomfort, strain and spasms. Some 
386 
uncommon side effects include dizziness, allergic reaction to electrodes, 
387 
bruising from being positioned, lower or elevated blood pressure, increased 
388 
heart rate, shortness of breath, pain or discomfort. Rarely, burns to the skin 
389 
from electrodes, bone fractures during exercise training have also been reported. 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
Page 10 of 17 
 
 
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Risk associated with magnetic stimulation: Single-pulse transcranial magnetic 
392 
stimulation is generally considered safe. However, there is a very low risk of 
393 
seizure. Therefore, you should not participate if you have any history of seizures 
394 
or epilepsy. Due to the magnetic field, your arms and shoulders may move 
395 
during the stimulation and may experience shoulder and/or neck ache. There is 
396 
a loud sound from the stimulation machine that may be startling but is not 
397 
dangerous. 
398 
Magnetic stimulation (cervical and transcranial) is a safe and non-invasive 
399 
nerve stimulation technique that has been used in clinical and research 
400 
settings for over 30 years. The risks associated with magnetic stimulation are 
401 
minimal; however, you may feel discomfort during the stimulations, including 
402 
shoulder or neck ache for cervical stimulations. If you are uncomfortable with 
403 
the  higher  intensities  of  stimulation,  please  let your study team know   
404 
and extended breaks will be given, or if desired, no further stimulations will  
405 
be performed. Using single-pulse TMS, even the highest stimulation setting is  
406 
not harmful. There is a clicking sound that may be startling but is not  
407 
dangerous. Although rare, seizures are a potential side effect of single-pulse  
408 
TMS. In the event of a seizure or other medical emergency, emergency  
409 
services (911) will be called. 
410 
411 
Additionally, researchers will take appropriate steps to protect any information 
412 
they collect about you. All data collected will be stored in secured locations 
413 
such as a locked filing cabinets, on secured, password-protected computer 
414 
servers, or on encrypted electronic storage devices. However, there is a slight 
415 
risk that information about you could be revealed inappropriately or 
416 
accidentally. Depending on the nature of the information, such a release could 
417 
upset or embarrass you, or possibly affect your ability to be insured or 
418 
employed. Questions 8 and 9 in this form discuss what information about you 
419 
will be collected, used, protected, and shared. 
420 
421 
This Research Study may also include risks that are unknown at this time. 
422 
Please note, participating in more than one research study or project may 
423 
further increase the risks to you. If you are already enrolled in a research 
424 
study, please inform one of the Research Team members or the person 
425 
reviewing this consent with you before enrolling in this or any other research 
426 
study or project. 
427 
428 
During the study, the Research Team will notify you of new information that 
429 
may become available and might affect your decision to remain in the study. 
430 
431 
The Thomas Jefferson University is required by law to protect your health 
432 
information. Your health information will be stored in locked filing cabinets or 
433 
on computer servers with secure passwords, or encrypted electronic storage 
434 
devices, as required by University policy. However, there is a slight risk that 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
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435 
information about you could be released inappropriately or accidentally. 
436 
Depending on the type of information, a release could upset or embarrass you, 
437 
or possibly affect your ability to get insurance or a job. 
438 
439 
A new Federal law, called the Genetic Information Nondiscrimination Act 
440 
(GINA), generally makes it illegal for health insurance companies, group health 
441 
plans, and most employers to discriminate against you based on your genetic 
442 
information. This law generally will protect you in the following ways: 
443 
444 
• Health insurance companies and group health plans may not request 
445 
your genetic information that we get from this research. 
446 
• Health insurance companies and group health plans may not use your 
447 
genetic information when making decisions regarding your eligibility or 
448 
premiums. 
449 
• Employers with 15 or more employees may not use your genetic 
450 
information that we get from this research when making a decision to hire, 
451 
promote, or fire you or when setting the terms of your employment. 
452 
453 
All health insurance companies, and group health plans must follow this law 
454 
by May 21, 2010. All employers with 15 or more employees must follow this 
455 
law as of November 21, 2009. Be aware that this new Federal law does not 
456 
protect  you  against  genetic  discrimination  by  companies  that  sell  life 
457 
insurance, disability insurance, or long-term care insurance. 
458 
459 
To help us protect your privacy, we have obtained a Certificate of 
460 
Confidentiality from the National Institutes of Health. With this Certificate, the 
461 
researchers cannot be forced to disclose information that may identify you, 
462 
even by a court subpoena, in any federal, state, or local civil, criminal, 
463 
administrative, legislative, or other proceedings. The researchers will use the 
464 
Certificate to resist any demands for information that would identify you, 
465 
except as explained below. 
466 
467 
The Certificate cannot be used to resist a demand for information from 
468 
personnel of the United States Government that is used for auditing or 
469 
evaluation  of  federally  funded  projects  or  for  information  that  must  be 
470 
disclosed in order to meet the requirements of the federal Food and Drug 
471 
Administration (FDA). 
472 
473 
474 
Risks of Blood Draw 
475     For most people, having blood taken is quick, easy and relatively painless. 
476 
Other people may feel anxious and occasionally the participant may feel 
477 
unwell or faint. Therefore, you will be asked to stay under study staff 
478 
supervision until you fully recover after a blood draw. Some people have a 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
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479 
tendency to bruise at the site of venipuncture. In order to prevent, a cotton- 
480 
wool dressing will be taped over the puncture site and you will also be asked 
481 
to avoid carrying anything heavy or undertake strenuous exercise within 24 
482 
hours of the blood sample collection. 
483 
 
484 
485 
Strength testing risks 
486 
Your hand and breathing muscles can develop temporary soreness following 
487 
muscle strength testing. Any muscle soreness related to muscle testing should 
488 
subside within 24 to 48 hours. If muscle pain persist longer than 48 hours 
489 
please inform the study personal who will refer you the study physician. 
490 
491 
Other possible risks to you may include: The electrode gel used during 
492 
electrode placement is slightly abrasive and may cause skin irritation. We 
493 
encourage participants to inform the researcher of any skin conditions and 
494 
discomfort during electrode placement. 
495 
496 
497 
Costs 
498 
499 
You may have costs for participating in this study. 
500 
501 
There will be no study related items or services billed to you or your insurance 
502 
company. There is no plan to pay you for lost wages, lost time from work, 
503 
personal discomfort, or for injuries or problems related to your underlying 
504 
medical condition(s). If you receive a bill that you think is incorrect,  
505 
please contact the research personnel. You will be responsible to pay for your  
506 
travel to and from the study site and other out-of-pocket expenses such as  
507 
parking. 
507 
508 
Research-Related Injury 
509 
510 
There is a possibility that you could have research-related injury, which is an 
511 
illness or an injury that is directly caused by the study procedure. If you have 
512 
a research-related injury, we will offer you reasonable and necessary care to 
513 
treat injuries directly resulting from taking part in this research. Neither 
514 
Jefferson nor the study will pay for costs associated with treatment of research- 
515 
related injury or illness. These costs may be billed to your insurance. In 
516 
addition, you will be responsible for any deductibles and co-payments required 
517 
under your health plan and for any claims ultimately denied by your health 
518 
plan. 
519 
520 
There are no plans for Jefferson to pay you or give you other compensation for 
521 
the injury. However, you are not prevented 
from seeking 
to collect 
522 
compensation for injury related to malpractice, fault, or blame on the part of 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
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523 
those involved in the research. If you think you have been injured as a result 
524 
of taking part in this research study, tell the research personnel as soon as 
525 
possible. Please see the contact information in this consent form. 
526 
527 
Disclosure of Financial Interest 
528 
529 
There are no conflicts of interest to report in this study. 
530 
531 
Privacy and Confidentiality:  HIPAA Authorization 
532 
533 
Information will be collected about you for this study.  The information will be 
534 
seen by the people involved with this research. Steps will be taken to protect 
535 
your identity. But the information collected about you can never be 100% 
536 
secure. 
537 
538 
HIPAA (Health Insurance Portability and Accountability Act) – This is the law 
539 
that protects your personal health information. 
540 
541 
To do this study, we need to collect, use, and share your personal health 
542 
information. This form will explain why your information is being collected, 
543 
what information will be collected, and who will have access to it. By signing, 
544 
you are giving us permission to use your information as described in this form. 
545 
546 
We are committed to respecting your privacy and to keeping your personal 
547 
health information confidential. Your personal health information includes the 
548 
information in your health care records and information that can identify you. 
549 
For example, personal information may include your name, address, phone 
550 
number, social security number, and medical information. The personal health 
551 
information that may be collected, used, and shared for this research includes: 
552 
553 
• Information from your medical records 
554 
• Demographic information such as name, gender, birth date, ethnicity, 
555 
medical history, and health care providers 
556 
• Physical examinations, procedures, tests, labs, your medical conditions, 
557 
and medications you use 
558 
• Information collected about any research related injury 
559 
• Information about mental health, sexually transmitted diseases, HIV, 
560 
AIDS, drug and alcohol use, genetic test results, and other sensitive 
561 
information 
562 
• Biomarker Sampling (blood, saliva) 
563 
564 
Your personal information will be used by and shared with the following: 
565 
566 
• Personnel  at  Thomas  Jefferson  University  and  its  affiliates  for  the 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
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567 
purpose of this research 
568 
• Research personnel at Rothman 
569 
• Institutional Review Boards (ethics committees that review research) 
570 
including the Thomas Jefferson University IRB 
571 
• Health insurance providers 
572 
• Research monitors hired by the sponsor to oversee the study and review 
573 
health care records to ensure study-related information is correct 
574 
• Government Agencies like the Food and Drug Administration (FDA) 
575 
• An organization such as a contract research organization (CRO) that has 
576 
been hired to coordinate the study 
577 
• Public health authorities who monitor such things 
as sexually 
578 
transmitted diseases, HIV, AIDS, child abuse, as required by law 
579 
• Groups monitoring the safety of the study such as a data and safety 
580 
monitoring committee 
581 
• Others as required by law 
582 
When your personal information is provided to some of the people listed, it 
583 
may no longer be protected under the HIPAA privacy law. You can see your 
584 
health care records at any time. However, generally you will not be able to see 
585 
your study records or the study results until the study is completed. A copy of 
586 
this signed form, information about this study, and the results of any study 
587 
test or procedure may be included in your health records which may be seen 
588 
by your insurance company and your health care providers. 
589 
590 
This  authorization  does  not  have  an  expiration  date.  Please  inform  the 
591 
investigator  in  writing  if  you  want  to  end  your  permission  to  collect 
592 
information/samples. Please note that anything already collected will still be 
593 
used and you may not be able to continue in this study. 
594 
595 
The information from this study may be published in scientific journals or 
596 
presented at scientific meetings, but you will not be personally identified. 
597 
598 
A description of this study will be available on http://www.ClinicalTrials.gov, 
599 
as required by U.S. Law. This website will not include information that can 
600 
identify you. At most, the website will include a summary of the results. You 
601 
can search this website at any time. 
602 
603 
Your private information and specimens, with the identifiers removed, could 
604 
be used for future research studies or distributed to other researchers for 
605 
future research studies without your additional permission. 
606 
607 
Contacts 
608 
If you are having a medical emergency, call 911 or go directly to an 
609 
emergency room. You should let emergency personnel or providers 
610 
know that you are taking part in this study. 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
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611 
612 
For Questions About: Person or Office 
Contact Information 
The Study or Research 
Investigator: 
Related Injury 
Jayakrishnan Nair, PT, 
352-871-5888 
PhD 
 
Mijail Serruya, MD, 
215-964-7276 
PhD 
Dana R. Johnson, PT, DPT 215-868-1988 
If you need to contact 
Jefferson Center City 
215-503-0203 
someone other than the 
study personnel about a Institutional Review 
215-503-8966 
concern or your rights 
as a 
Board (Ethics 
research subject 
Committee) 
215-955-4239 
613 
614 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
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615 
Signatures 
616 
617 
Patient/Subject: By signing this form, you are agreeing that: 
618 
619 
620 
621 
622 
623 
624 
• You were given the opportunity to read this form. 
• All of the information in this form was discussed with you by an 
investigator or other research personnel to your satisfaction. 
• All your questions have been answered to your satisfaction. 
• You were not pressured and you voluntarily agree to take part in 
this research.  
625 
 
 
626 
 
627 
_______________      __________________      _________ 
628 
629 
630 
Your Name                Your Signature                   Date 
 
 
631 
 
      _______________      __________________      _________ 
  Name of Person           Signature of Person                 Date 
 Obtaining/Assisting         Obtaining/Assisting  
  with Consent                  with Consent  
 
637 By signing below, you the investigator, certify that you, a co-investigator, or 
638 
other properly trained and qualified key personnel, reviewed the elements of 
639 
consent with the study participant. 
640 
641 
 
       _______________      __________________      _________ 
 Name of Investigator     Signature of Investigator       Date       
 
 
645 
       _______________      __________________      _________ 
 Name of Witness          Signature of Witness             Date      
 
649 
(Witness required if the only language the subject speaks and understands is 
650 
English, but the subject cannot read English, or if the subject is blind or cannot 
651 
physically sign the consent form.) 
652 
653 
Copy of 
Signed 
and 
Dated 
Consent 
Form Given 
to 
the 
654 
 
Subject/Parent/LAR 
 
 
 
 

PI: Dr. Jayakrishnan Nair, PT, PhD 
IRB Control #: iRISID-2023-1796 
Sponsor: Jefferson 
Abbreviated Title: Combinatorial Therapy SCI 
Version Date: 07/16/2023 
Version Number: 2.0 
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   655 Optional Teach-Back Questions – These questions can be asked to help 
656 
ensure that the patient understands the study. 
 
657 
Check this box if these questions were reviewed with the patient. 
 
658 
We have gone over a lot of information. I would like to ask you a few 
659 
questions to make sure I have done a good job explaining the study to you. 
 
660 
1. In your own words, please answer these questions about this study: 
 
661 
a. Why are we doing this study (what are we trying to learn)? 
 
662 
b. What things (including tests and procedures) will you have to do 
663 
in this study? 
 
664 
c. What are some of the risks of being in this study? 
 
665 
d. What is the benefit of being in this study? 
 
666 
e. How will being in this study be different than usual medical care? 
 
667 
f. How long will you be in this study? 
 
668 
2. Taking part in this study is voluntary. What does that mean to you? 
 
669 
a. If you don’t want to be in this study, what are your other 
670 
choices? 
 
671 
b. What will happen if you chose not to be in this study? 
 
 
 
672 
3. What will we do to make sure your information remains confidential? 
 
673 
4. What other questions do you have about this study?