Chronic Stroke
Conditions
Keywords
robotics, transcranial direct current stimulation, neurorehabilitation, transcranial magnetic stimulation
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.
Detailed 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.
Interventions
DEVICETranscranial 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.
DEVICEUpper 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.
Sponsors
Beth Israel Deaconess Medical Center
Feinstein Institute for Medical Research
Massachusetts Institute of Technology
Spaulding Rehabilitation Hospital
Burke Medical Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Masking description
Staff delivering the transcranial direct current stimulation and performing evaluations are blinded to active vs. sham stimulation.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Upper Limb Fugl Meyer Score | Baseline and after the 12-week intervention | 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. |
Participant flow
Recruitment details
CVA's identified (n=1600) * Excluded on initial screen (n=859) 425 with residential proximity to studying site contacted * Excluded for the following reasons (n=343) Randomized (n=82) Robot Sham (n=41) * Included in the post 6 months analysis (n=35) Robot tDCS (n=41) * Included in the post 6 months analysis (n=34)
Participants by arm
| Arm | Count |
|---|---|
| Active tDCS 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.
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. | 41 |
| Sham tDCS 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.
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. | 41 |
| Total | 82 |
Baseline characteristics
| Characteristic | Active tDCS | Sham tDCS | Total |
|---|---|---|---|
| Age, Continuous | 66.0 years | 70.0 years | 68.5 years |
| Fugl-Meyer score | 22.0 units on a scale | 21.5 units on a scale | 21.8 units on a scale |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Male | 25 Participants | 25 Participants | 50 Participants |
| Time since stroke | 1201 days | 654 days | 852.5 days |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 41 | 4 / 41 |
| serious Total, serious adverse events | 0 / 41 | 0 / 41 |
Outcome results
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.
Time frame: Baseline and after the 12-week intervention
Population: Of the 41 enrolled for active tDCS, 1 was lost due to unrelated illness and could not complete assessment after the 12-week intervention. Only 40 participant's data were included in the analysis. Of the 41 enrolled for Sham tDCS, 1 person was excluded due to Botox treatment, 2 people were excluded due to unrelated illness and 1 other person was excluded due to related illness. Only 37 participant's data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active tDCS | Change From Baseline in Upper Limb Fugl Meyer Score | 7.0 Units on a scale | Standard Deviation 4 |
| Sham tDCS | Change From Baseline in Upper Limb Fugl Meyer Score | 7.7 Units on a scale | Standard Deviation 4.9 |