Brain Stimulation and Robotics in Chronic Stroke Motor Recovery

Chronic Stroke Clinical Trial

Official title:

Transcranial Direct Current Stimulation and Robotic Training in Chronic Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03562663
• Other study ID #: BRC426
• Status: Completed
• Phase: N/A
• Start date: January 2012
• Est. completion date: December 2016

Study information

• Verified date: December 2020
• Source: Burke Medical Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Motor skill training and transcranial direct current stimulation (tDCS) have separately been shown to alter cortical excitability and enhance motor function in humans. Their combination is appealing for augmenting motor recovery in stroke patients, and this is an area presently under heavy investigation globally. The investigators have previously shown that the timing of tDCS application has functional significance, that tDCS applied prior to training can be beneficial for voluntary behavior, and that tDCS effects may not simply be additive to training effects, but may change the nature of the training effect. The investigators have separately reported in a randomized-controlled clinical trial, that upper limb robotic training alone over 12 weeks can improve clinical function of chronic stroke patients. Based on our results with tDCS and robotic training, the investigators hypothesize that the same repeated sessions of robotic training, but preceded by tDCS, would lead to a sustained and functional change greater than robotic training alone. The investigators will determine if clinical function can be improved and sustained with tDCS-robotic training and cortical physiology changes that underlie functional improvements.

Description:

The primary aim of this study is to evaluate whether multiple sessions of combined tDCS and robotic upper limb training in chronic hemiplegia, leads to clinical improvement in upperlimb motor impairment. In chronic stroke patients (>6months post-injury, stable unilateral motor deficit) using a within-subjects repeated-measures design we will evaluate the effects of 12 weeks of robotic upperlimb training (3x/week, 36 sessions, shoulder/elbow/wrist in each session) with real or sham tDCS before the robotic training. Clinical improvement will be determined by a change in upper-limb Fugl-Meyer (primary), the Medical Research Council motor power score (MRC), Wolf Motor Function Test, Barthel Index, and Stroke Impact Scale (secondary) outcome measures following the training, and assessed again six months later.

The investigators further aim to identify and compare the neurophysiological characteristics between intervention groups. The relationship between clinical improvement and neurophysiological measures pertaining to robotic motor training following stroke are presently not described in the literature. By measuring the EMG response from forearm musculature to Transcranial Magnetic Stimulation the investigators will establish: (i) plasticity associated with training, and (ii) the neurophysiological characteristics of patients who respond to training. By understanding how brain excitability changes underpin motor dysfunction, and motor recovery, interventions can be more effectively prescribed and prognoses established.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: December 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• A first single focal unilateral lesion with diagnosis verified by brain imaging (MRI or CT scans) that occurred at least 6 months prior;

• Ability to follow 1-2 step commands

• Fugl-Meyer assessment of 7 to 58 out of 66 (neither hemiplegic nor fully recovered motor function in the muscles of the shoulder and elbow and wrist).

Exclusion Criteria:

• A fixed contraction deformity in the affected limb;

• A complete and total flaccid paralysis of all shoulder and elbow motor performance;

• A hemorrhagic stroke

• Presence of tDCS / TMS risk factors

• Presence of an electrically, magnetically or mechanically activated implant (including cardiac pacemaker), an intracerebral vascular clip, or any other electrically sensitive support system

• A history of medication-resistant epilepsy in the family

• Past history of seizures or unexplained spells of loss of consciousness

Related Conditions & MeSH terms

• Chronic Stroke
• Stroke

Intervention

Device:
• Transcranial direct current stimulation
A constant, low current stimulation is provided non-invasively through sponge electrodes positioned over the motor cortex of the affected arm. The stimulation is provided for 20 minutes at an intensity of 2 mA.
• Upper extremity robotics
Participants complete robotic training 3 days per week for 12 weeks, or 36 sessions. The protocol alternates between planar (shoulder/elbow) and wrist robots for the duration of the study.

Locations

Country	Name	City	State
n/a

Sponsors (5)

Lead Sponsor	Collaborator
Burke Medical Research Institute	Beth Israel Deaconess Medical Center, Feinstein Institute for Medical Research, Massachusetts Institute of Technology, Spaulding Rehabilitation Hospital

References & Publications (18)

Fitzgerald PB, Fountain S, Daskalakis ZJ. A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition. Clin Neurophysiol. 2006 Dec;117(12):2584-96. Epub 2006 Aug 4. Review. — View Citation

Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, Rigonatti SP, Marcolin MA, Freedman SD, Nitsche MA, Pascual-Leone A. Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport. 2005 Sep 28;16(14):1551-5. — View Citation

Heide G, Witte OW, Ziemann U. Physiology of modulation of motor cortex excitability by low-frequency suprathreshold repetitive transcranial magnetic stimulation. Exp Brain Res. 2006 May;171(1):26-34. Epub 2005 Nov 24. — View Citation

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. Epub 2005 Jan 5. — View Citation

Iyer MB, Mattu U, Grafman J, Lomarev M, Sato S, Wassermann EM. Safety and cognitive effect of frontal DC brain polarization in healthy individuals. Neurology. 2005 Mar 8;64(5):872-5. — View Citation

McCreery DB, Agnew WF, Yuen TG, Bullara L. Charge density and charge per phase as cofactors in neural injury induced by electrical stimulation. IEEE Trans Biomed Eng. 1990 Oct;37(10):996-1001. — View Citation

Nitsche MA, Liebetanz D, Lang N, Antal A, Tergau F, Paulus W. Safety criteria for transcranial direct current stimulation (tDCS) in humans. Clin Neurophysiol. 2003 Nov;114(11):2220-2; author reply 2222-3. — View Citation

Nitsche MA, Niehaus L, Hoffmann KT, Hengst S, Liebetanz D, Paulus W, Meyer BU. MRI study of human brain exposed to weak direct current stimulation of the frontal cortex. Clin Neurophysiol. 2004 Oct;115(10):2419-23. — View Citation

Pascual-Leone A, Valls-Solé J, Wassermann EM, Hallett M. Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain. 1994 Aug;117 ( Pt 4):847-58. — View Citation

Priori A. Brain polarization in humans: a reappraisal of an old tool for prolonged non-invasive modulation of brain excitability. Clin Neurophysiol. 2003 Apr;114(4):589-95. — View Citation

Talelli P, Rothwell J. Does brain stimulation after stroke have a future? Curr Opin Neurol. 2006 Dec;19(6):543-50. Review. — View Citation

Tassinari CA, Cincotta M, Zaccara G, Michelucci R. Transcranial magnetic stimulation and epilepsy. Clin Neurophysiol. 2003 May;114(5):777-98. Review. — View Citation

Volpe BT, Krebs HI, Hogan N, Edelsteinn L, Diels CM, Aisen ML. Robot training enhanced motor outcome in patients with stroke maintained over 3 years. Neurology. 1999 Nov 10;53(8):1874-6. — View Citation

Volpe BT, Krebs HI, Hogan N. Robot-aided sensorimotor training in stroke rehabilitation. Adv Neurol. 2003;92:429-33. Review. — View Citation

Ward NS, Cohen LG. Mechanisms underlying recovery of motor function after stroke. Arch Neurol. 2004 Dec;61(12):1844-8. Review. — View Citation

Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol. 1998 Jan;108(1):1-16. — View Citation

Webster BR, Celnik PA, Cohen LG. Noninvasive brain stimulation in stroke rehabilitation. NeuroRx. 2006 Oct;3(4):474-81. Review. — View Citation

Yuen TG, Agnew WF, Bullara LA, Jacques S, McCreery DB. Histological evaluation of neural damage from electrical stimulation: considerations for the selection of parameters for clinical application. Neurosurgery. 1981 Sep;9(3):292-9. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Upper Limb Fugl Meyer Score	Upper limb fugl Meyer score is a measure of upper extremity motor weakness on a 66-point scale.; Fugl Meyer score range: 0-66. Higher scores indicate better outcome. Units: Units on a scale.	Baseline and after the 12-week intervention