Efficacy of rTMS on Pain Following Stroke.

Study Overview
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Brief Summary
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Pain is a common symptom experienced by people following stroke and can significantly interfere with participation in the activities of daily living and adversely affect health-related quality of life. Repetitive Transcranial Magnetic Stimulation (rTMS) promotes the modulation of brain activity and its prolonged and continuous application can effect plastic modification. Combining rTMS with rehabilitation treatment for primary motor cortex activation (using Gloreha® device) may have effect in reducing pain in stroke survivors. This is a pilot randomized control trial to test the effects of rTMS in stroke-related pain rehabilitation, its efficacy on pain, upper limb function, sensory function and autonomy in daily livings activities. Furthermore, we will explore the effects on pressure pain threshold, cortical excitability and EEG recording.

Official Title
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Efficacy of rTMS on Pain Following Stroke: a Pilot Randomized Control Trial.

Conditions
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Stroke

Intervention / Treatment
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* Device: Real-rTMS + Gloreha device
* Device: Sham-rTMS + Gloreha device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of first stroke verified by brain imaging < 6 months pain defined as a constant or intermittent sensory symptom with unpleasant feelings or pain and a minimum score of 3 points on the Numeric Rating Scale (NRS) for pain perception Exclusion Criteria: medical conditions likely to interfere with the ability to safely complete the study protocol cognitive functioning to give informed consent identified by a Mini-Mental Status Examination (MMSE) score ≥ 24/30 intracranial metal implants history of seizures or epilepsy severe cardiopulmonary, renal, and hepatic diseases pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Real-rTMS + Gloreha device<br> | Device: Real-rTMS + Gloreha device<br>* The real rTMS will be delivered using a 8-shaped coil placed over the primary motor cortex (M1). The resting motor threshold (RMT) will be assessed at the place of the first dorsal interosseous (FDI) contralateral to the stimulated cortex. RMT of the FDI will be determined as the lowest strength of TMS needed to elicit 5 or more electromyographic responses ≥50 μV within 10 trials. Stimulation will be applied with frequency 10 Hz and intensity of 90% of RMT. Every session will last 15 minutes and includes 3000 pulses (30 trains of 10 seconds, following intertrain interval of 20 seconds). Rehabilitation programme will last 30 minutes and will be delivered using Gloreha® device, a proprioceptive stimulator under visual feedback. All the subjects enrolled will receive treatments for 2 weeks, 5 days per week.<br>|
| Active Comparator: Sham-rTMS + Gloreha device<br> | Device: Sham-rTMS + Gloreha device<br>* The sham rTMS will be delivered using a sham stimulator. All procedures will be performed as for the real treatment. Rehabilitation programme will last 30 minutes and will be delivered using Gloreha® device, a proprioceptive stimulator under visual feedback. All the subjects enrolled will receive treatments for 2 weeks, 5 days per week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Rating Scale (NRS) | Core outcome measure of pain intensity in pain treatments' clinical trials | Change measures (weeks: 0,2,6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropathic Pain Symptom Inventory (NPSI) | A self-questionnaire specifically designed to evaluate the different symptoms of neuropathic pain. | Change measures (weeks: 0,2,6) | 
| Short Form McGill Pain Questionnaire (SF-MPQ) | Assessment of sensory and affective dimensions of typical whole-body pain intensity. | Change measures (weeks: 0,2,6) | 
| Beck Depression Inventory II (BDI-II) | Assessment of severity of common depressive symptoms. | Change measures (weeks: 0,2,6) | 
| Erasmus MC modification to the (revised) Nottingham Sensory Assessment - Italian version (EmNSA-I) | Assessment of sensory function following brain injury. | Change measures (weeks: 0,2,6) | 
| Fugl-Meyer Assessment - Upper Extremity (FM-UE) | Assessment of upper limb function. | Change measures (weeks: 0,2,6) | 
| Barthel Index (BI) | Scale that measures disability or dependence in activities of daily living in stroke patients. | Change measures (weeks: 0,2,6) | 
| Pressure Pain Threshold (PPT) | PPT is measured to test presence of widespread pressure hyperalgesia as sign of abnormal pain processing. | Change measures (weeks: 0,2,6) | 
| Electroencephalography (EEG) recordings | EEG data will be recorded to test presence of particular brain activity in condition of pain. | Change measures (weeks: 0,2,6) | 
| Motor cortex excitability (single pulse TMS) | Single pulse TMS will be used to study cortical-spinal tract excitability in primary motor cortex (M1). | Change measures (weeks: 0,2,6) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, rTMS, Rehabilitation