Effects of Transcutaneous Spinal Direct Current Stimulation in Incomplete Spinal Cord Injury

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Transcutaneous Spinal Direct Current Stimulation in Incomplete Spinal Cord Injury

Conditions
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Incomplete Spinal Cord Injury

Intervention / Treatment
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* Device: Anodal tsDCS
* Device: Cathodal tsDCS
* Device: Sham tsDCS


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover design with 9 arms: Anodal tsDCS, Cathodal tsDCS, Sham tsDCS
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anode, then Cathode, then Anode, then Sham, then Cathode tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|
| Experimental: Sham, then Cathode, then Anode, then Anode, then Cathode tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|
| Experimental: Anode, then Cathode, then Sham, then Anode, then Cathode tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|
| Experimental: Cathode, then Anode, then Cathode, then Anode, then Sham tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|
| Experimental: Anode, then Anode, then Sham, then Cathode, then Cathode tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|
| Experimental: Sham, then Anode, then Cathode, then Cathode, then Anode tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|
| Experimental: Cathode, then Anode, then Cathode, then Sham, then Anode tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|
| Experimental: Sham, then Anode, then Cathode, then Anode, then Cathode tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|
| Experimental: Cathode, then Cathode, then Sham, then Anode, then Anode tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|
| Experimental: Anode, Then Cathode, Then Anode, Then Cathode Then Sham tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|
| Experimental: Sham, Then Anode, Then Anode, Then Cathode, Then Cathode tsDCS<br>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. | Device: Anodal tsDCS<br>* 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.<br>Device: Cathodal tsDCS<br>* 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.<br>Device: Sham tsDCS<br>* During Sham tsDCS intervention, battery will be turned off and no current will pass through the electrodes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 10 minutes before intervention, 10 minutes after intervention | 
| 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. | 30 to 40 minutes before intervention, 30 to 40 minutes after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change Systolic Blood Pressure | Systolic Blood pressure will be recorded before and after each tsDCS session. | 60 to 90 minutes before intervention, 60 to 90 minutes after intervention | 
| Change in Diastolic Blood Pressure | Diastolic Blood pressure will be recorded before and after delivering each intervention | 60 to 90 minutes before intervention,60 to 90 minutes after intervention ( for each intervention) | 
| Change in Heart Rate | Heart rate will be recorded before and after delivering each intervention | 60 to 90 minutes before intervention,60 to 90 minutes after intervention ( for each intervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Incomplete SCI