Enhancement of Motor Function With Reboxetine and Transcranial Direct Current Stimulation

Study Overview
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Brief Summary
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The hypothesis of the study is that combination of reboxetine/tDCS is more effective in enhancing motor functions of daily life (assessed by the Jebsen Taylor test) as compared to reboxetine and tDCS alone. The protocol is designed as a within-subject, block randomized placebo-controlled double-blind crossover study.

Detailed Description
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One important feature of the human brain is the ability to undergo plastic changes and reorganization after learning and lesions of the nervous system. This ability is of major importance for the treatment of functional deficits after stroke. Stroke is the major disease leading to persistent functional disabilities in Germany. However, the success rate of therapeutic interventions, especially in chronic stroke patients, is still unsatisfactory. Thus, basic science is essential to discover new therapeutic options that bear the potential for translation into clinical practice. Recent evidence is pointing to modulating the motor cortical excitability in order to enhance motor function in stroke patients. For this purpose, reboxetine as a selective reuptake inhibitor of noradrenaline and transcranial direct current stimulation have proven effective in enhancing motor functions needed for daily life activities by 10-12%. These improvements were significant compared to placebo, but still clinically unsatisfactory. Thus, this protocol aims at enhancing the excitability modulatory effect of each single intervention through the combination of reboxetine and tDCS. The hypothesis of the study is that combination of reboxetine/tDCS is more effective in enhancing motor functions of daily life (assessed by the Jebsen Taylor test) as compared to reboxetine and tDCS alone. The protocol is designed as a within-subject, block randomized placebo-controlled double-blind crossover study. 12 chronic stroke patients with persistent functional deficits of the arm and/or hand will be included. The primary outcome measure is the time needed to fulfill all subtests of the Jebsen Taylor test. All patients undergo four different conditions in four different sessions: 1) reboxetine + verum tDCS; 2) reboxetine + sham tDCS 3) placebo drug + verum tDCS 4) placebo drug + sham tDCS.

Official Title
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Entwicklung Neuronaler Repräsentationen Nach Schlaganfall: Verbesserung Motorischer Leistungen Durch Transkranielle Gleichstromstimulation Und Noradrenerge Co-Stimulation

Conditions
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Cerebral Stroke

Intervention / Treatment
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* Drug: reboxetine
* Drug: Placebo
* Device: tDCS verum
* Device: tDCS sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age between 18 and 86 patient is contractually capable first-ever, ischemic stroke minimum time since stroke 9 months a paresis of the arm/hand muscles above 3 on the MRC scale Exclusion Criteria: multiple cerebral lesions and associated residual deficits severe head trauma in the past seizures ferromagnetic implants in the head/neck region pacemaker a psychiatric disorder or neurological disease besides stroke intake of illegal drugs severe aphasia or cognitive deficits that impede contractual capability contraindications for reboxetine (seizures, glaucoma, prostate hyperplasia with urinary retention, cardiac arrhythmias, potential interactions with co-medication) pregnancy breast-feeding patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 86 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>reboxetine + tDCS verum | Drug: reboxetine<br>* single dose of 4mg reboxetine 80 minutes before assessment of Jebsen Taylor test<br>* Other names: brand name: Edronax, serial number: KPR 08092410/11;Device: tDCS verum<br>* 20 minutes of 1 mV transcranial direct current stimulation with 5x5 cm electrodes with active electrode over the primary motor representation of the stroke hemisphere and reference electrode over the contralateral supraorbital area Application during assessment of Jebsen Taylor test<br>* Other names: Serialnumber: 0006;|
| Experimental: 2<br>reboxetine + sham tDCS | Drug: reboxetine<br>* single dose of 4mg reboxetine 80 minutes before assessment of Jebsen Taylor test<br>* Other names: brand name: Edronax, serial number: KPR 08092410/11;Device: tDCS sham<br>* 30 seconds of 1 mV transcranial direct current stimulation with 5x5 cm electrodes with active electrode over the primary motor representation of the stroke hemisphere and reference electrode over the contralateral supraorbital area Application during assessment of Jebsen Taylor test<br>* Other names: Serialnumber: 0006;|
| Experimental: 3<br>placebo drug + verum tDCS | Drug: Placebo<br>* placebo, 80 min before assessment of Jebsen Taylor test<br>Device: tDCS verum<br>* 20 minutes of 1 mV transcranial direct current stimulation with 5x5 cm electrodes with active electrode over the primary motor representation of the stroke hemisphere and reference electrode over the contralateral supraorbital area Application during assessment of Jebsen Taylor test<br>* Other names: Serialnumber: 0006;|
| Experimental: 4<br>placebo drug + sham tDCS | Drug: Placebo<br>* placebo, 80 min before assessment of Jebsen Taylor test<br>Device: tDCS sham<br>* 30 seconds of 1 mV transcranial direct current stimulation with 5x5 cm electrodes with active electrode over the primary motor representation of the stroke hemisphere and reference electrode over the contralateral supraorbital area Application during assessment of Jebsen Taylor test<br>* Other names: Serialnumber: 0006;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Jebsen Taylor test |  | crossover design, four different sessions with four different interventions | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum grip force |  | crossover design, four different sessions with four different interventions | 
| nine hole peg test |  | crossover design, four different sessions with four different interventions | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, reboxetine, noradrenaline, motor cortex, transcranial direct current stimulation, motor function, rehabilitation, Jebsen Taylor test