Transcranial Magnetic Stimulation (TMS) for Upper Limb Dysfunction in Spinal Cord Injury: a Feasibility Study

Study Overview
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Brief Summary
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This study will investigate how repetitive transcranial magnetic stimulation (TMS) using intermittent theta-burst stimulation (iTBS) paradigm affects sensorimotor dysfunction such as pain, spasticity, motor weakness and sensory loss. TMS is technique which allows non-invasive stimulation of the cortex, and can modulate activity of neurons. The purpose of this study will be to assess the feasibility of using TMS with iTBS paradigm to treat sensorimotor dysfunction in people with incomplete spinal cord injury affecting the upper limbs.

Official Title
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Feasibility Study to Investigate the Effects of Transcranial Magnetic Stimulation (TMS) Using Theta Burst Stimulation (TBS) to Treat Upper Limb Dysfunction and Spasticity in Patients With Spinal Cord Injury

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation using iTBS Paradigm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-70 years old inclusive Traumatic and non-traumatic tetraplegic patient following chronic incomplete (AIS C or D) SCI injury (sustained at least three months ago) Referred to the Sheffield Spinal Injuries Centre Be able to provide written informed consent or verbal consent in the presence of an independent witness Spasticity affecting upper limbs with a Modified Ashworth scale (MAS) 2 or above Stable medical treatment for at least 1 week before and 1 week after TMS application Stable medical condition Exclusion Criteria: Aged less than 18 years old Lack the mental capacity to consent Ventilated patients with sedation Very acute (<3 months) SCI patients Implanted electrical devices such as pacemakers, Concomitant neurological conditions, including any history of epilepsy Significant joint-related limitation of passive range of movement Unable to attend all TMS sessions Pregnancy Inability to tolerate TBS Significant upper limb contractures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active iTBS<br>iTBS will be delivered using the 50Hz, 600 pulses protocol for 10 sessions over a period of two weeks. The hand representation of the primary motor cortex will targeted using a circular coil held over the vertex of skull. Intensity will be set to 80% of Resting Motor Threshold (RMT), which will be determined visually by the lowest percentage of stimulator output which can cause upper limb motor twitch in at least 5 out of 10 attempts. | Device: Transcranial Magnetic Stimulation using iTBS Paradigm<br>* TMS is a non-invasive, painless method of stimulating the central and peripheral nervous system. ITBS is a form of TMS which is delivered for  200sec and can promote changes in neural activity.<br>* Other names: repetitive Transcranial Magnetic Stimulation;|
| Sham Comparator: Sham iTBS<br>Sham iTBS will be delivered using the 50Hz, 600 pulses protocol for 10 sessions over a period of two weeks. Intensity will be set at 80% RMT. Circular coil will be held over vertex of skull but angled away to ensure no neural stimulation. | Device: Transcranial Magnetic Stimulation using iTBS Paradigm<br>* TMS is a non-invasive, painless method of stimulating the central and peripheral nervous system. ITBS is a form of TMS which is delivered for  200sec and can promote changes in neural activity.<br>* Other names: repetitive Transcranial Magnetic Stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility Criteria 1: Number of participants recruited | Recruitment of 20 participants within 6 months (i.e. 3 - 4 participants per month) | Through to study completion, up to 6 months | 
| Feasibility Criteria 2: Number of participants completing intervention protocol | 10 participants completing full intervention protocol | Through to study completion, up to 6 months | 
| Feasibility Criteria 3: Number of Valid data sets | 10 complete valid data sets | Through to study completion, up to 6 months | 
| Feasibility Criteria 4: Number of Serious Adverse Events Experienced by Participants | No serious adverse events | Through to study completion, up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Ashworth Scale (MAS) | MAS is a clinical assessment of spasticity. Spasticity of wrist extensors, flexors, elbow extensors and flexors of both upper limbs will be assessed. | Baseline and 2 weeks | 
| Range of Motion (RoM) | Active RoM of wrist extension, flexion, elbow extension and flexion of both of both upper limbs will be measured using a goniometer. | Baseline and 2 weeks | 
| Leeds Arm Spasticity Impact Scale (LASIS) | Questionnaire assessing impact of spasticity on a person. | Baseline and 2 weeks | 
| Visual Analogue Scale (Spasticity) (VAS-S) | A 100mm line with two statements at each end (No spasticity, worst spasticity). The patient will mark on the line their own perception of how bad they feel their spasticity is. | Baseline and 2 weeks | 
| American Spinal Injuries Association Impairment Scale (AIS) (Inc. grading, upper extremity motor score, lower extremity motor score, light touch and pin prick scores) | A clinical assessment of sensory dermatomes and key muscle groups of upper and lower limbs. | Baseline and 2 weeks | 
| Spinal Cord Independence Measure (SCIM) - Version 3 | scale developed to address the ability of SCI patients to perform basic activities of daily living independently. | Baseline and 2 weeks | 
| Visual Analogue Scale (Pain) - (VAS-P) | A 100mm line with two statements at each end (no pain, worst pain). The patient will mark on the line their own perception of how bad they feel their pain is. | Baseline and 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transcranial magnetic stimulation, Spinal Cord Injuries, Muscle Spasticity, Pain, Spinal Cord, Spinal Cord Diseases