Effects of Transcutaneous Spinal Direct Current Stimulation in Incomplete Spinal Cord Injury
Phase: NA
Conditions: Incomplete Spinal Cord Injury
Sponsor: The University of Texas Health Science Center, Houston

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IRB NUMBER: HSC-MS-17-0166 
IRB APPROVAL DATE: 08/18/2017 
 
 
 
 
 
 
 
 
 
 
 
Effects of trans-cutaneous spinal direct current stimulation in incomplete spinal cord injury 
 
NCT03249454 
 
Version Date: 08/18/2017 
 
 

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IRB NUMBER: HSC-MS-17-0166 
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UNIVERSITY OF TEXAS – HOUSTON MEDICAL SCHOOL PROTOCOL 
 
PROTOCOL TITLE: Effects of trans-cutaneous spinal direct current stimulation in 
incomplete spinal cord injury 
 
2. 
BACKGROUND and SIGNIFICANCE 
According to the National Spinal Cord Injury Statistical Center, as many as 300,000 people in the 
United States are living with spinal cord injury (SCI), with approximately 17,000 new cases each year.1 
Unfortunately, efforts to minimize neurologic damage in acute SCI have met with only limited 
success.2, 3 Complete recovery is reported in less than 1% of SCI survivors.1 Thus, there is a need for 
interventions to enhance recovery of function for people living with chronic effects of SCI. Recovery of 
motor function after chronic SCI has been associated with neuroplastic changes.4, 5 
Transcranial direct current stimulation has been shown to significantly influence corticomotor 
excitability (a marker of neuroplasticity).6-9 The polarity of the current is important in direct current 
stimulation: anodal stimulation over the primary motor cortex leads to a depolarization of the neuronal 
membrane’s resting potential and thus increases motor cortical excitability; cathodal stimulation 
causes the opposite effect.10-12 Early human and animal studies suggest similar modulation of spinal 
cord excitability after transcutaneous spinal direct current stimulation (tsDCS). Possible mechanisms 
include alteration of GABAergic and glutamatergic systems.13-22 However, data in this regard is very 
limited and inconsistent.18, 19, 22, 23 This study addresses this gap in research by conducting a 
exploratory project that will evaluate the effects of tsDCS on spinal excitability. This pilot study will 
provide preliminary support and effect sizes that will be used in a larger federally funded study 
Many symptoms and signs of SCI, such as hyperreflexia and spasticity are associated with H- 
reflex alteration.24 Therefore, demonstrating changes in the amplitude of H reflexes might be of 
potential clinical importance since these changes have been related to the acquisition of new 
motor skills and in restoration of motor functions in both animals and humans.25-29  The H-reflex 
is used commonly to study the excitability of spinal motor circuitry as a surrogate for functional 
adaptation and neuroplastic changes that may occur in relation to injury, disease, or therapeutic 
interventions.26, 30-32 Thus, given the previous finding that tsDCS can alter H reflex22 we 
hypothesize that tsDCS is capable of inducing plastic changes of excitability in the 
monosynaptic pathway mediating the H-reflex, when tested using stimulation rates at which 
post-activation depression is present. 
SSEPs after stimulation of posterior tibial nerve are absent in complete lesions of the spinal 
cord. However, incomplete lesions yield varying abnormalities on SSEPs. Latencies and 
amplitudes of tibial SSEPs can change over time after spinal cord injury (SCI). SSEPs have 
been studied as a surrogate measure to evaluate for neuroplasticity after cortical and spinal 

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cord stimulation.17, 33, 34 However, there are no robust studies that evaluated effects of tsDCS on 
SSEPs. 
In sum, and in contrast to most other studies of tsDCS, our design expedites early-stage 
investigation of this promising intervention by establishing strong, electrophysiological data prior 
to rapid clinical translation of findings. In general, our proposal has exceedingly high 
translational potential. The non-invasive stimulation we propose (tsDCS) is delivered by a 
portable device that can be easily carried and applied in a diversity of clinical settings, including 
inpatient and outpatient rehabilitation. 
 
3. 
PURPOSE OF THE STUDY: 
The purpose of the study is to investigate the effects of a novel therapeutic approach to promote 
functional recovery and spasticity in chronic SCI. We will evaluate tsDCS effect on neuro- 
physiological measure such as H reflex and SSEP in subjects with SCI. This incremental, 
design will allow us to establish strong, electrophysiological data prior to rapid clinical translation 
of our findings about this promising, early-stage technique. 
The central hypothesis is twofold: 1) active tsDCS will lead to a change in Hmax/M max ratio 
than sham tsDCS, in a polarity dependent manner; and 2) active tsDCS will lead to a change in 
SSEP amplitude and latency, in a polarity dependent manner. 
Hypothesis: To evaluate the effects of tsDCS and different polarities on spinal excitability as 
measured by change in Hmax/M max ratio and SSEPs. 
Hypothesis 1: In subjects with motor incomplete SCI, either anodal or cathodal tsDCS placed 
at the T10-T11 level will result in a change in spinal excitability evident by change in Hmax/M 
max ratio. 
Hypothesis 2: In subjects with motor incomplete SCI, either anodal or cathodal tsDCS placed 
at the T10-T11 level will result in a change in spinal excitability evident by change in 
somatosensory evoked potential (SSEP). 
 
4. 
DESCRIPTION OF STUDY: 
Subjects will be screened in the outpatient SCI clinic. Each subject will receive five tsDCS (2 
cathodal, 2 anodal and 1 sham) conditions at T10-T11 spinal level in a random order. There will 
be a wash-out period of 1 week between each tsDCS condition. Saline soaked sponge 
electrodes (36 cm2) will be used to deliver active tsDCS over skin at specified level. Reference 
electrode will be placed over left shoulder. Active tsDCS (i.e., anodal or cathodal; not sham) will 
consist of stimulation at an intensity of 2.5 mA for the entirety of each stimulation session (i.e., 
2.5mA for 15 minutes to result in a current density of 0.071mA/cm2 and a total delivered charge 
of 0.064C/cm2). This current density was proven to be safe and sufficient to induce 

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physiological changes in previous human studies.17, 19, 35 .In a study done on healthy subjects 
(Korupolu PI), current densities above this range resulted in skin blisters. For sham tsDCS, we 
will start at 0mA and ramp the intensity up, then down, over a 30-second window. This protocol 
has proven effectiveness for blinding subjects in studies applying direct current stimulation. 
 
Pre-screening: During the pre-screening process, potential subjects with incomplete SCI will be 
contacted by phone or in person by Dr. Korupolu (PI) or other co-investigators. Dr.Korupolu will 
give final approval for the subject to come to The Institute for Rehabilitation and Research 
Memorial Hermann for the screening procedure. 
 
Screening (Visit 1, duration: One hour): This visit will occur the same day as intervention 
visit. After subject arrives at TIRR a research personnel will meet him/her at the Motor Recovery 
Laboratory. The details of the study- specific procedures will be reviewed with the subject 
together. Subject will be screened for inclusion and exclusion criteria. Signed and dated 
informed consent will be obtained. Demographics, medical history, list of medications and 
modified ashworth scale score will be recorded. If the subject is female in child bearing ages, a 
urine pregnancy test results from primary care physician will be requested. A medication diary 
will be given to the subject and asked to document all changes in type and dosage of the 
medication he/she has been using throughout the study. This will allow us to differentiate a 
potential effect of a change in dosage or type of medication on movement recovery. After 
subject meets all Inclusion an Exclusion Criteria the randomization will be done by means of 
sealed, opaque, consecutively numbered envelopes constructed by the research assistant. 
Each envelope will have intervention sequence information. Sequence will be generated by a 
random number generator. The research assistant will assign 1 envelope to each subject 
randomly. Each envelope will be opened by the research assistant prior to first session who will 
administer tsDCS. The research assistant will not be involved in data analysis or measurement 
of outcomes. 
Intervention (duration: three hours): This visit is divided in to baseline, tsDCS stimulation and 
post tsDCS. 
 
 
Figure1 : Intervention Visit: Baseline Hmax/Mmax and SSEP will be performed before actual tsDCS intervention. Post 

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intervention Hmax/Mmax and SSEP will be performed after the tsDCS 
 
Baseline: The baseline assessment will be performed on the same visit as intervention and will 
be performed in the Motor Recovery Laboratory by an evaluator blinded to subject’s group 
assignment. 
Vital Signs: Vital signs will be recorded at the beginning of each session. 
SSEPs: We will measure SSEPs to evaluate effects of tsDCS on ascending 
somatosensory pathways. A somatosensory evoked potential (SSEP) is the electrical 
activity response measured at the skin’s surface along ascending sensory pathway 
following controlled peripheral nerve stimulation. For recording posterior tibial nerve 
SSEPs, the nerve is stimulated at the ankle, with the cathode midway between the 
Achilles tendon and the medial malleolus and the anode 3 cm distal to the cathode. 
Nerve stimulation should consist of a 0.1–0.2 ms duration square wave pulse at 3-5Hz. 
These pulses will be delivered by constant voltage stimulator applied transcutaneously 
over the targeted nerve. The stimulation intensity would exceed the motor threshold for 
eliciting a muscle twitch.37We will use same Nihon Kohden clinical EMG/NCV measuring 
system to measure SSEPs. Procedure will follow per clinical protocol. 
 
Hmax/Mmax ratio: Immediately before and after application of tsDCS we will measure 
Hmax/Mmax ratio obtained from soleus muscle by stimulation of tibial nerve. The 
difference between pre and post Hmax/Mmax ratio will be measured. The H-reflex is a 
compound muscle action potential elicited by low-threshold electrical stimulation of 
afferent fibers in the mixed nerve with subsequent monosynaptic excitation of alpha 
motoneurons. Changes in the excitability of the reflex pathway are estimated by 
measuring the amplitude of the reflex. M wave is a compound muscle action potential 
produced by direct supra-maximal stimulation of motor axons. The H-reflex amplitude is 
highly variable, the excitability of the motoneuron pool plays a substantial role in 
determining the amplitude of the H-reflex. Therefore, changes in the ratio of maximal H- 
reflex amplitude and maximal M-wave amplitude (Hmax/Mmax) provide a rough estimate 
of modulation in spinal excitability.18, 19, 22 It is necessary to normalize this value so 
between-subject comparisons can be made. These amplitude variations can result from 
variations in skin resistance, different amounts of subcutaneous fat, and locations of the 
nerve relative to the stimulus, among others. The most advocated method of H-reflex 
normalization is eliciting the H-reflex at a percentage of the Mmax. This method entails 
finding the amplitude of the Mmax and then adjusting the stimulation intensity to produce 
an H-reflex with amplitude equal to some percentage of the Mmax amplitude.36 

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Figure 2: M wave and Hreflex 
M wave 
H reflex 

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tsDCS Stimulation: Spinal stimulation direct current will be delivered by a battery-driven direct 
current stimulator (Soterix Medical, Model 0707-A) connected to a pair of saline-soaked sponge 
electrodes Each subject will receive five tsDCS conditions at T10-T11 spinal level with a wash- 
out period of 1 week between 2 cathodal, 2 anodal and 1 sham tsDCS in a random order. Saline 
soaked sponge electrodes (36 cm2) will be used to deliver active tsDCS over skin at specified 
level. Reference electrode will be placed over left shoulder. Active tsDCS (i.e., anodal or 
cathodal; not sham) will consist of stimulation at an intensity of 2.5 mA for the entirety of each 
stimulation session (i.e., 2.5mA for 15 minutes to result in a current density of 0.071mA/cm2 and 
a total delivered charge of 0.064C/cm2). This current density was proven to be safe and 
sufficient to induce physiological changes in previous human studies.17, 19, 35 In a study done on 
healthy subjects (Korupolu PI), current densities above this range resulted in skin blisters. For 
sham tsDCS, we will start at 0mA and ramp the intensity up, then down, over a 30-second 
window. This protocol has proven effectiveness for blinding subjects in studies applying direct 
current stimulation. Figure 3 shows the study design. 

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Figure 3 Study Design:Randomization 
 
Post tsDCS: Hmax/Mmax ratio, SSEP and vital signs will be recorded. Similar 
procedures will be followed as pre intervention assessments for Hmax/Mmax ratio, 
SSEP and vital signs recordings. 
Adverse events: Any adverse events during intervention and collection of pre and post 
intervention outcomes assessments will be collected. 

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Assessment 
Screening 
Intervention 1 
(Anodal or 
Cathodal or 
Sham) 
Washo 
ut 
Intervention 2 
(Anodal or 
Cathodal or 
Sham) 
Washou 
t 
Intervention 3 
(Anodal or 
Cathodal or 
Sham) 
Washo 
ut 
Intervention 4 
(Anodal or 
Cathodal or 
Sham) 
Washout 
Intervention 
5 
(Anodal or 
Cathodal or 
Sham) 
 
0-30 days 
prior 
Session1 
atleast 
8 days 
Session 2 
atleast 
8 days 
Session 3 
atleast 
8 days 
Session4 
atleast 8 
days 
Session5 
ICF 
X 
I/E Criteria 
X 
Randomization 
X 
Demographics 
X 
Medical 
History 
X 
Modified 
Ashworth 
Scale 
X 
Baseline Vital 
Signs 
X 
X 
X 
X 
X 
Baseline SSEP 
X 
X 
X 
X 
X 
Baseline 
Hmax/Mmax 
X 
X 
X 
X 
X 
tsDCS 
X 
X 
X 
X 
X 
Post SSEP 
X 
X 
X 
X 
X 
Post 
Hmax/Mmax 
X 
X 
X 
X 
X 
Post Vital 
Signs 
X 
X 
X 
X 
X 
Questionnaire 
X 
X 
X 
X 
X 
Adverse 
Events 
X 
X 
X 
X 
X 

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Table 1: Schedule of visits for SCI participant. 
 
 
 
 
 
 
5. 
SUBJECT POPULATION: 
Fifteen adults with SCI will be recruited from TIRR Memorial Hermann, TIRR Outpatient 
Rehabilitation at Kirby Glen and from the Houston area. 
 
Inclusion Criteria: 
1. Providing written informed consent prior to any study related procedures; 
2. 18-65 years of age; 
3. Motor incomplete SCI classified as B, C or D by the American Spinal Injury Association 
Impairment Scale (AIS); 
4. Traumatic lesion at or above T8-T9 neurological level 
5. Body mass index ≤ 30 (in order to facilitate reliable location of body landmarks guiding 
stimulation); 
6. Chronic SCI (time since injury>6 months) 
 
Exclusion Criteria: Subjects will be excluded if they have following conditions 
1. Unstable cardiopulmonary conditions; 
2. History of seizure, head injury with loss of consciousness, severe alcohol or drug abuse, 
and/or psychiatric illness; 
3. Any joint contracture or severe spasticity, as measured by a Modified Ashworth Score 4; 
4. Subject who cannot provide self-transportation to the study location; 
5. Cardiac or neural pacemakers; 
6. Pregnancy 
7. h/o lower motor neuron injury (eg: peripheral neuropathy, cauda equina syndrome) 
8. Uncontrolled diabetes with HbA1C>7; 
9. History of severe autonomic dysreflexia; 
10. alteration in therapy or medication for muscle tone during the course of the study(botulinum 
toxin injections in last 3 months, phenol injections in last 6 months, intrathecal baclofen pump 
dose stable for past 3 months, etc); 
11. Conditions for e.g., severe arthritis, extreme shoulder pain that would interfere with valid 
administration of the measures or with interpreting motor testing; 
12. contraindications to tsDCS: 
- ferromagnetic material in the brain or in the spine (except for titanium used in segmental 9 

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fixation of the spine) 
- implanted brain medical devices 
6. 
SUBJECT ENROLLMENT: 
 
Potential subjects will be identified by the following sources: 
 
1- Flyers will be posted in the TIRR Memorial Hermann outpatient clinic, TIRR Memorial 
Herman Adult and Pediatric Outpatient Rehabilitation Kirby Glen, MHH Rehabilitation Centers. 
Attending physicians and therapists may refer their acquired brain injury outpatients to the 
study. In order to reach out to individuals with SCI; flyers will be distributed through an e-mail 
distribution. 
2- After subjects are identified by their treating physicians and therapists, they will be referred to 
the co-investigator. During this first contact, the researcher will briefly explain the study content 
and request their phone number and e-mail address to contact them later for a pre-screening. 
During a phone call, a brief pre-screening procedure will be followed. Demographics and 
medical information such as surgery implants, medications, psychiatric, drug and alcohol history 
as inclusion and exclusion criteria will be gathered. Dr. Korupolu will review the information 
gathered during phone screening and may request screening. 
3- Potential subjects will be invited to come for a screening visit to Motor Recovery Laboratory 
at TIRR Memorial Hermann. Any information gathered during phone screening will be stored in 
a locked file cabinet and password protected electronic file. During the screening visit, an 
investigator at TIRR will obtain informed consent. The test procedures will be described and the 
testing equipment will be shown to the subject. Investigator will clearly explain all the 
procedures and risks of the testing outlined in the consent form. The subject will be given 
sufficient time to consider their decision and will be encouraged to ask questions, both during 
the initial interview and throughout the study. The PI or a co-investigator will answer any 
questions regarding the study at the time consent is given. Once enrolled, the subject may 
pause or terminate his/her participation at any time during the study. 
4- Alternatively any person with SCI who are living in the community and been informed through 
flyers can contact the researchers directly and request more information about the study. 
 
 
7. 
DATA ANALYSIS: 
Data analysis: Descriptive statistics will be calculated for all variables. Group analysis of 
intervention-related changes with fixed effects comparison of post-intervention versus baseline 
will be performed. We will use repeated measures analysis of covariance to estimate the effect 

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of group on outcome measures. Stata 14 software will be used to perform analysis. PI has 
training to use stata software to perform above analysis. 
A sample size of 15 subjects was determined based on the review of current literature to 
determine the optimal polarity for future studies.17, 19, 22, 35 In these studies 10-12 healthy subjects 
were evaluated who received one anodal tsDCS, one cathodal tsDCS and sham (total 3 
sessions) in cross over fashion. In our study, we plan to deliver 2 cathodal, 2 anodal and one 
sham session to each subject to improve the strength of the findings. We will have total 75 
sessions and 150 data points (pre and post tsDCS outcome assessment) for each outcome 
measure. This study will provide a strong neurophysiological data for the implementation of 
future clinical randomized controlled trial studies to evaluate the effects of tsDCS combined with 
rehabilitation therapy. 
8. 
POTENTIAL RISKS/DISCOMFORTS: 
 
tsDCS: Transcutaneous Spinal Direct Current Stimulation (tsDCS) is a noninvasive procedure 
in which a device sends a small Direct Current (DC) across the skin to modulate spinal function. 
The use of tsDCS in therapeutic protocols to date has not resulted in severe adverse effects. In 
addition our protocol of 2.5mA has been used by other researchers with no signficant adverse 
events 
SSEP: Somatosensory evoked potential is recording electrical signals of sensation going from 
body to brain. Recording electrodes are attached to the scalp and arm. The stimulus will last 
about 2 minutes at a time and may cause some twitching and tingling sensation in the target 
area. However it is painless and carries no significant risk. 
Spinal reflexes measurement: Stimuli above the action threshold of peripheral nerves will be 
administered through skin. This might cause some discomfort that is anticipated to be mild and 
easily tolerated by the subjects. Also skin irritation might occur due to electrode attachment to 
the skin. 
Assessment/Questionnaires: All assessments will be performed in a designated room inside 
Motor Recovery Laboratory. None of these tests are either painful or uncomfortable to perform. In 
order to prevent potential embarrassment during the testing the test will be done individually and 
in private. If subjects feel uncomfortable in answering any of the questions they may stop the 
study at any time. 
 
9. POTENTIAL BENEFITS: 
As with any study focusing on basic research, the subjects will derive no direct benefit. The 
results of these studies may benefit subsequent future subjects. We envision that in the near 
future the information obtained from the proposed research will provide a better understanding 

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for treatment options of SCI population. 
 
10. RISK-BENEFIT RATIO: 
The potential improvement of arm and hand movement outweighs the risk of non-invasive spine 
stimulation, fatigue, pain and discomfort. 
 
11. CONSENT PROCEDURES: 
Informed consent will be obtained from the subject at Motor Recovery Laboratory at The 
Institute for Rehabilitation and Research. After the patient is identified by the PI and her 
research team study criteria and he/she is interested in participating, informed, written consent 
will be obtained by a member of the research team. 
In addition a photography/videotaping consent will be obtained from the subject, if he/she 
agrees to be photographed / videotaped during the assessments or treatment sessions. 
12. CONFIDENTIALITY PROCEDURE: 
All data will be coded with identification number, database will be in a password –protected 
computer and kept in a locked file cabinet. 
13. COSTS 
The subject will not be expected to pay any costs. 
14. PAYMENTS: 
Subject receive up to $75 to help cover the cost of transportation and parking if they 
attend all five of your scheduled sessions. 
 
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