Brain Stimulation and Robotics in Chronic Stroke Motor Recovery

NCT03562663 | Completed Results FDA Device

• 1 other identifier: BRC426
• Study Type: interventional
• Target: 82
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Chronic Stroke

Keywords

robotics; transcranial direct current stimulation; neurorehabilitation; transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Active tDCS

EXPERIMENTAL

Participants in this group received 20 minutes of active 2 mA transcranial direct current stimulation over the motor cortex of the affected arm prior to robotic intervention.

Device: Transcranial direct current stimulation; Device: Upper extremity robotics

Sham tDCS

SHAM COMPARATOR

Participants in this group received 20 minutes of sham 2 mA transcranial direct current stimulation over the motor cortex of the affected arm prior to robotic training.

Device: Upper extremity robotics

Interventions

Transcranial direct current stimulation DEVICE

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.

Active tDCS

Upper extremity robotics DEVICE

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.

Active tDCS; Sham tDCS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Burke Medical Research Institute: lead
• Beth Israel Deaconess Medical Center: collaborator
• Feinstein Institute for Medical Research: collaborator
• Massachusetts Institute of Technology: collaborator
• Spaulding Rehabilitation Hospital: collaborator

Related Publications (20)

• 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. doi: 10.1007/s00221-005-0262-0. Epub 2005 Nov 24.

  PMID: 16307247 BACKGROUND

• 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. doi: 10.1016/j.clinph.2006.06.712. Epub 2006 Aug 4.

  PMID: 16890483 BACKGROUND

• 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. doi: 10.1097/01.wnr.0000177010.44602.5e.

  PMID: 16148743 BACKGROUND

• 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.

  PMID: 15634731 BACKGROUND

• 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. doi: 10.1212/01.WNL.0000152986.07469.E9.

  PMID: 15753425 BACKGROUND

• 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. doi: 10.1109/10.102812.

  PMID: 2249872 BACKGROUND

• 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. doi: 10.1016/s1388-2457(03)00235-9. No abstract available.

  PMID: 14580622 BACKGROUND

• 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. doi: 10.1016/j.clinph.2004.05.001.

  PMID: 15351385 BACKGROUND

• Pascual-Leone A, Valls-Sole 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. doi: 10.1093/brain/117.4.847.

  PMID: 7922470 BACKGROUND

• 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. doi: 10.1016/s1388-2457(02)00437-6.

  PMID: 12686266 BACKGROUND

• Talelli P, Rothwell J. Does brain stimulation after stroke have a future? Curr Opin Neurol. 2006 Dec;19(6):543-50. doi: 10.1097/WCO.0b013e32801080d1.

  PMID: 17102691 BACKGROUND

• Tassinari CA, Cincotta M, Zaccara G, Michelucci R. Transcranial magnetic stimulation and epilepsy. Clin Neurophysiol. 2003 May;114(5):777-98. doi: 10.1016/s1388-2457(03)00004-x.

  PMID: 12738425 BACKGROUND

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

  PMID: 12760210 BACKGROUND

• 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. doi: 10.1212/wnl.53.8.1874.

  PMID: 10563646 BACKGROUND

• Ward NS, Cohen LG. Mechanisms underlying recovery of motor function after stroke. Arch Neurol. 2004 Dec;61(12):1844-8. doi: 10.1001/archneur.61.12.1844.

  PMID: 15596603 BACKGROUND

• 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. doi: 10.1016/s0168-5597(97)00096-8.

  PMID: 9474057 BACKGROUND

• Webster BR, Celnik PA, Cohen LG. Noninvasive brain stimulation in stroke rehabilitation. NeuroRx. 2006 Oct;3(4):474-81. doi: 10.1016/j.nurx.2006.07.008.

  PMID: 17012061 BACKGROUND

• 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.

  PMID: 7301072 BACKGROUND

• Moretti CB, Hamilton T, Edwards DJ, Peltz AR, Chang JL, Cortes M, Delbe ACB, Volpe BT, Krebs HI. Robotic Kinematic measures of the arm in chronic Stroke: part 2 - strong correlation with clinical outcome measures. Bioelectron Med. 2021 Dec 29;7(1):21. doi: 10.1186/s42234-021-00082-8.

  PMID: 34963502 DERIVED

• Moretti CB, Edwards DJ, Hamilton T, Cortes M, Peltz AR, Chang JL, Delbem ACB, Volpe BT, Krebs HI. Robotic Kinematic measures of the arm in chronic Stroke: part 1 - Motor Recovery patterns from tDCS preceding intensive training. Bioelectron Med. 2021 Dec 29;7(1):20. doi: 10.1186/s42234-021-00081-9.

  PMID: 34963501 DERIVED

MeSH Terms

Interventions

Transcranial Direct Current Stimulation

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Results Point of Contact

• Title: Dylan Edwards
• Organization: Moss Rehabilitation Research Institute

EdwardDy@einstein.edu

(215) 663-6411

Study Officials

• Dylan Edwards, PhD

  Moss Rehabilitation Institute

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Staff delivering the transcranial direct current stimulation and performing evaluations are blinded to active vs. sham stimulation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lab Director, Laboratory for Non-Invasive Brain Stimulation and Human Motor Control

Model Details: We conducted a double-blind, sham-controlled, repeated-measures study design evaluating the effects of 12 weeks of robot-assisted upper-limb training (3x/week, 36 sessions) with tDCS (Robot-tDCS) or sham tDCS (Robot-Sham ) delivered at rest before each robot-assisted training session.

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: June 19, 2018
• Study Start: January 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 20, 2021
• Results First Posted: January 20, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share