Low-frequency Transcranial Magnetic Stimulation To Enhance Motor Recovery In The Subacute Phase After Stroke

Study Overview
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Brief Summary
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Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere (UH) transiently improves motor function in patients in the chronic phase after stroke. The goal of this study is to investigate effects on motor recovery of low-frequency rTMS of the UH, administered in the subacute phase after stroke.

Detailed Description
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Stroke is a major cause of disability and worldwide. Hand motor impairment is frequent after stroke. Even mild impairments of the upper limb negatively impact disability and quality of life in these patients significantly contributes to disability. Therapeutic alternatives for hand motor rehabilitation are deeply needed. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential tool to improve hand motor performance after stroke. While high-frequency rTMS (HF-rTMS) often increases motor cortical excitability, LF-rTMS often has the opposite effect. Up-regulation of excitability in the affected hemisphere by HF-rTMS or down-regulation of the UH by LF-rTMS can restore the balance in inter-hemispheric inhibition and hence, facilitate movement of the paretic hand Both strategies, as well as the combination of both, have yielded encouraging results when applied in proof-of-principle, single-session studies to patients with mild hand motor impairment in the subacute and chronic stages after stroke. However, few rTMS studies included patients less than six months after stroke, and effects of LF-rTMS of the unaffected hemisphere in patients with severe motor impairment in the subacute phase have not been yet reported. The investigators opted for a novel approach to enhance hand motor recovery, by examining feasibility, safety and preliminary efficacy of either active or sham LF-rTMS of the UH or sham rTMS as add-on therapies to outpatient customary rehabilitation, to patients with mild to severe hand paresis, within 5-45 days after unilateral ischemic stroke. The investigators hypothesize that, at this stage, LF-rTMS will be feasible even in patients with severe motor deficits, will have minimal adverse events and will enhance effects of customary rehabilitation on hand motor performance.

Official Title
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Low-frequency Transcranial Magnetic Stimulation To Enhance Motor Recovery In The Subacute Phase After Stroke

Conditions
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Stroke

Intervention / Treatment
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* Other: Repetitive transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First-ever ischemic stroke in the internal carotid artery territory confirmed by CT or MRI, 5-45 days before, leading to contralateral hand weakness Age, 18-80 years Exclusion Criteria: Cardiac pacemaker Pregnancy Implantable medication pump Intracranial hypertension History of seizures Metal in the head Decompressive surgery Other neurological diseases Shoulder pain Joint deformity in the paretic upper limb Severe chronic disease such as end-stage cancer or end-stage renal failure Inability to provide informed consent due to severe language or cognitive impairment

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active rTMS<br>1Hz active rTMS delivered to the unaffected hemisphere | Other: Repetitive transcranial magnetic stimulation<br>* Repetitive transcranial magnetic stimulation, frequency of 1Hz, once a day for ten days.<br>|
| Placebo Comparator: Placebo rTMS<br>1Hz placebo rTMS delivered to the vertex | Other: Repetitive transcranial magnetic stimulation<br>* Repetitive transcranial magnetic stimulation, frequency of 1Hz, once a day for ten days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor function of the paretic hand evaluated with the Jebsen-Taylor test |  | Baseline, two weeks, 1 month, 3 and six months after end of treatment | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability |  | Baseline, two weeks, 1 month, 3 and six months after end of treatment | 
| Number of patients able to comply with the protocol |  | Baseline, two weeks, 1 month, 3 and six months after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Force of the paretic hand |  | Baseline, two weeks, 1 month, 3 and six months after end of treatment | 
| Fugl-Meyer evaluation of motor performance (upper limb) |  | Baseline, two weeks, 1 month, 3 and six months after end of treatment | 
| Disability evaluated with the modified Rankin scale |  | Baseline, two weeks, 1 month, 3 and six months after end of treatment | 
| Functional Independence Measure |  | Baseline, two weeks, 1 month, 3 and six months after end of treatment | 
| Neurological impairment evaluated with the NIH Stroke Scale |  | Baseline, two weeks, 1 month, 3 and six months after end of treatment | 
| Measures of corticomotor excitability evaluated with transcranial magnetic stimulation |  | Baseline, two weeks, 1 month, 3 and six months after end of treatment |