Incomplete Spinal Cord Injury
Conditions
Keywords
Incomplete SCI
Brief summary
The purpose of the study is to investigate the effects of a novel therapeutic approach with transcutaneous spinal direct current stimulation (tsDCS) to promote functional recovery and spasticity in chronic spinal cord injury (SCI).
Detailed description
The purpose of the study is to investigate the effects of a novel therapeutic approach to promote functional recovery and spasticity in chronic SCI. The tsDCS effect on neuro-physiological measures such as H reflex and somatosensory evoked potential (SSEP) wiil be evaluated in subjects with SCI. This incremental, design will allow the establishment of strong electrophysiological data prior to rapid clinical translation of the 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.
Interventions
DEVICEAnodal tsDCS
During Anodal tsDCS intervention the positive end of the battery will be connected to the electrode on participant's back and negative end of the battery will be connected to the electrode on participant's shoulder. The battery will be turned on for 15 minutes, and the stimulation strength will be adjusted a couple of times per tolerance level.
DEVICECathodal tsDCS
During Cathodal tsDCS intervention the negative end of the battery will be connected to the electrode on participant's back and positive end of the battery will be connected to the electrode on participant's shoulder. The battery will be turned on for 15 minutes, and the stimulation strength will be adjusted a couple of times per tolerance level.
DEVICESham tsDCS
During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.
Sponsors
TIRR/Mission Connect
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Crossover design with 9 arms: Anodal tsDCS, Cathodal tsDCS, Sham tsDCS
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Providing written informed consent prior to any study related procedures * 18-65 years of age * Motor incomplete SCI classified as B, C or D by the American Spinal Injury Association Impairment Scale (AIS) * Traumatic lesion at or above T8-T9 neurological level * Body mass index ≤ 30 (in order to facilitate reliable location of body landmarks guiding stimulation); * Chronic SCI (time since injury\>6 months)
Exclusion criteria
* Unstable cardiopulmonary conditions * History of seizure, head injury with loss of consciousness, severe alcohol or drug abuse, and/or psychiatric illness * Any joint contracture or severe spasticity, as measured by a Modified Ashworth Score 4 * Subject who cannot provide self-transportation to the study location * Cardiac or neural pacemakers * Pregnancy * lower motor neuron injury (eg: peripheral neuropathy, cauda equina syndrome) * Uncontrolled diabetes with HbA1C\>7 * History of severe autonomic dysreflexia * No planned alteration in therapy or medication for muscle tone during the course of the study(No botulinum toxin injections in last 3 months, No phenol injections in last 6 months, intrathecal baclofen pump dose stable for past 3 months, etc) * Conditions for e.g., severe arthritis, extreme shoulder pain that would interfere with valid administration of the measures or with interpreting motor testing; * No contraindications to tsDCS * ferromagnetic material in the brain or in the spine (except for titanium used in segmental)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Hmax | 10 minutes before intervention, 10 minutes after intervention | Immediately before application of tsDCS and after application of tsDCS, Hmax will be obtained from soleus muscle by stimulation of tibial nerve. 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. |
| Change in Somatosensory Evoked Potential (SSEP) | 30 to 40 minutes before intervention, 30 to 40 minutes after intervention | 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 by tsDCS. 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 3-5 Hertz (Hz). 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. Electromyogram (EMG)/ Nerve Conduction Velocity (NCV) measuring system will be used to measure SSEPs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change Systolic Blood Pressure | 60 to 90 minutes before intervention, 60 to 90 minutes after intervention | Systolic Blood pressure will be recorded before and after each tsDCS session. |
| Change in Diastolic Blood Pressure | 60 to 90 minutes before intervention,60 to 90 minutes after intervention ( for each intervention) | Diastolic Blood pressure will be recorded before and after delivering each intervention |
| Change in Heart Rate | 60 to 90 minutes before intervention,60 to 90 minutes after intervention ( for each intervention) | Heart rate will be recorded before and after delivering each intervention |
Countries
United States
Participant flow
Recruitment details
We recruited 15 subjects.
Pre-assignment details
2 enrolled participants were not assigned to an arm--one of these participant had leg edema that interfered with outcome assessment, and the second participant did not exhibit an H reflex due to a baclofen medication pump; therefore, these 2 participants were not randomized and did not start any intervention.
Participants by arm
| Arm | Count |
|---|---|
| All Participants 5 tsDCS sessions were performed for each subject, with at least a 1 week washout period between tsDCS sessions. For each session, the subject was randomly assigned to cathodal, anodal or sham tsDCS. Each subject who completed the study received 2 cathodal, 2 anodal and 1 sham tsDCS session. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 37.40 Years STANDARD_DEVIATION 13.27 |
| Employment Status Employed | 3 Participants |
| Employment Status Student | 1 Participants |
| Employment Status Unemployed | 11 Participants |
| Height | 173.05 centimeters STANDARD_DEVIATION 7.9 |
| Marital Status Divorced | 2 Participants |
| Marital Status Engaged | 1 Participants |
| Marital Status Married | 5 Participants |
| Marital Status Single | 7 Participants |
| Race/Ethnicity, Customized African American | 4 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 7 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Region of Enrollment United States | 15 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 12 Participants |
| Weight | 76.69 kilograms STANDARD_DEVIATION 16.92 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 0 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 | 1 / 15 | 0 / 15 |
Outcome results
Primary
Change in Somatosensory Evoked Potential (SSEP)
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 by tsDCS. 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 3-5 Hertz (Hz). 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. Electromyogram (EMG)/ Nerve Conduction Velocity (NCV) measuring system will be used to measure SSEPs.
Time frame: 30 to 40 minutes before intervention, 30 to 40 minutes after intervention
Population: Data was not collected for this outcome measure.
Primary
Percent Change in Hmax
Immediately before application of tsDCS and after application of tsDCS, Hmax will be obtained from soleus muscle by stimulation of tibial nerve. 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.
Time frame: 10 minutes before intervention, 10 minutes after intervention
Population: Those who completed the study were analyzed. Data are reported per session. There were potentially 22 cathode, 22 anode, and 11 sham sessions. Data for the Right Lower Extremity were not collected for 3 cathode, 3 anode, and 2 sham sessions, and data for the Left Lower Extremity were not collected for 3 cathode, 1 anode, and 2 sham sessions.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cathodal tsDCS | Percent Change in Hmax | Right Lower Extremity | 27.85 percent change in Hmax | Standard Deviation 63.57 |
| Cathodal tsDCS | Percent Change in Hmax | Left Lower Extremity | 16.20 percent change in Hmax | Standard Deviation 55.37 |
| Anodal tsDCS | Percent Change in Hmax | Right Lower Extremity | 8.43 percent change in Hmax | Standard Deviation 29.21 |
| Anodal tsDCS | Percent Change in Hmax | Left Lower Extremity | -3.99 percent change in Hmax | Standard Deviation 23.04 |
| Sham tsDCS | Percent Change in Hmax | Right Lower Extremity | -4.91 percent change in Hmax | Standard Deviation 39.12 |
| Sham tsDCS | Percent Change in Hmax | Left Lower Extremity | 34.04 percent change in Hmax | Standard Deviation 94.72 |
Secondary
Change in Diastolic Blood Pressure
Diastolic Blood pressure will be recorded before and after delivering each intervention
Time frame: 60 to 90 minutes before intervention,60 to 90 minutes after intervention ( for each intervention)
Population: Those who completed the study were analyzed. Data are reported per session. After randomization, there were potentially 22 cathode sessions, 22 anode sessions, and 11 sham sessions--of these sessions, data were not collected for 2 cathode sessions, 3 anode sessions, and 2 sham sessions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cathodal tsDCS | Change in Diastolic Blood Pressure | 4.80 millimeters of mercury (mmHg) | Standard Deviation 15.07 |
| Anodal tsDCS | Change in Diastolic Blood Pressure | 2.16 millimeters of mercury (mmHg) | Standard Deviation 6.65 |
| Sham tsDCS | Change in Diastolic Blood Pressure | -0.44 millimeters of mercury (mmHg) | Standard Deviation 9.06 |
Secondary
Change in Heart Rate
Heart rate will be recorded before and after delivering each intervention
Time frame: 60 to 90 minutes before intervention,60 to 90 minutes after intervention ( for each intervention)
Population: Those who completed the study were analyzed. Data are reported per session. After randomization, there were potentially 22 cathode sessions, 22 anode sessions, and 11 sham sessions--of these sessions, data were not collected for 2 cathode sessions, 3 anode sessions, and 2 sham sessions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cathodal tsDCS | Change in Heart Rate | -7.35 beats per minute (bpm) | Standard Deviation 5.28 |
| Anodal tsDCS | Change in Heart Rate | -6.53 beats per minute (bpm) | Standard Deviation 6.99 |
| Sham tsDCS | Change in Heart Rate | -4.78 beats per minute (bpm) | Standard Deviation 5.63 |
Secondary
Change Systolic Blood Pressure
Systolic Blood pressure will be recorded before and after each tsDCS session.
Time frame: 60 to 90 minutes before intervention, 60 to 90 minutes after intervention
Population: Those who completed the study were analyzed. Data are reported per session. After randomization, there were potentially 22 cathode sessions, 22 anode sessions, and 11 sham sessions--of these sessions, data were not collected for 2 cathode sessions, 3 anode sessions, and 2 sham sessions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cathodal tsDCS | Change Systolic Blood Pressure | 7.90 millimeters of mercury (mmHg) | Standard Deviation 13.31 |
| Anodal tsDCS | Change Systolic Blood Pressure | 7.58 millimeters of mercury (mmHg) | Standard Deviation 10.37 |
| Sham tsDCS | Change Systolic Blood Pressure | -4.00 millimeters of mercury (mmHg) | Standard Deviation 6.68 |