Enhancement of Motor Function With Reboxetine and Transcranial Direct Current Stimulation

Overview

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.

Full Title of Study: “Entwicklung Neuronaler Repräsentationen Nach Schlaganfall: Verbesserung Motorischer Leistungen Durch Transkranielle Gleichstromstimulation Und Noradrenerge Co-Stimulation”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: November 2009

Detailed Description

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.

Interventions

  • Drug: reboxetine
    • single dose of 4mg reboxetine 80 minutes before assessment of Jebsen Taylor test
  • Drug: Placebo
    • placebo, 80 min before assessment of Jebsen Taylor test
  • Device: tDCS verum
    • 20 minutes of 1 mV transcranial direct current stimulation with 5×5 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
  • Device: tDCS sham
    • 30 seconds of 1 mV transcranial direct current stimulation with 5×5 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

Arms, Groups and Cohorts

  • Experimental: 1
    • reboxetine + tDCS verum
  • Experimental: 2
    • reboxetine + sham tDCS
  • Experimental: 3
    • placebo drug + verum tDCS
  • Experimental: 4
    • placebo drug + sham tDCS

Clinical Trial Outcome Measures

Primary Measures

  • Jebsen Taylor test
    • Time Frame: crossover design, four different sessions with four different interventions

Secondary Measures

  • maximum grip force
    • Time Frame: crossover design, four different sessions with four different interventions
  • nine hole peg test
    • Time Frame: crossover design, four different sessions with four different interventions

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 86 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Universitätsklinikum Hamburg-Eppendorf
  • Collaborator
    • German Research Foundation
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Christian Gerloff, MD, Principal Investigator, Department of Neurology, University Hospital Hamburg-Eppendorf

References

Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, Cohen LG. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain. 2005 Mar;128(Pt 3):490-9. doi: 10.1093/brain/awh369. Epub 2005 Jan 5.

Hummel F, Cohen LG. Improvement of motor function with noninvasive cortical stimulation in a patient with chronic stroke. Neurorehabil Neural Repair. 2005 Mar;19(1):14-9. doi: 10.1177/1545968304272698.

Hummel FC, Voller B, Celnik P, Floel A, Giraux P, Gerloff C, Cohen LG. Effects of brain polarization on reaction times and pinch force in chronic stroke. BMC Neurosci. 2006 Nov 3;7:73. doi: 10.1186/1471-2202-7-73.

Plewnia C, Hoppe J, Gerloff C. No effects of enhanced central norepinephrine on finger-sequence learning and attention. Psychopharmacology (Berl). 2006 Aug;187(2):260-5. doi: 10.1007/s00213-006-0420-5. Epub 2006 Jun 10.

Plewnia C, Hoppe J, Cohen LG, Gerloff C. Improved motor skill acquisition after selective stimulation of central norepinephrine. Neurology. 2004 Jun 8;62(11):2124-6. doi: 10.1212/01.wnl.0000128041.92710.17.

Plewnia C, Hoppe J, Hiemke C, Bartels M, Cohen LG, Gerloff C. Enhancement of human cortico-motoneuronal excitability by the selective norepinephrine reuptake inhibitor reboxetine. Neurosci Lett. 2002 Sep 27;330(3):231-4. doi: 10.1016/s0304-3940(02)00803-0.

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