Cerebral Vascular Accident, Stroke
Conditions
Brief summary
The purpose of this study is to determine if transcranial direct current stimulation (tDCS)applied over the lower extremity motor cortex in conjunction with assisted gait training is effective for improving gait in patients with chronic stroke.
Interventions
DEVICEtranscranial direct current stim (tDCS)
During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down). During sham stimulation the stimulator is turned off.
Sponsors
University of Central Arkansas
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stroke survivors \> 3 months from most recent unilateral, stroke based on clinically or experimentally obtained MRI brain scans and behavioral evidence of stroke (e.g., risk factors, hemiplegia, unilateral sensory impairment, or localized higher cortical dysfunction) by report or in the medical record. * Age: \>21 years of age. * Complete NIH Stroke Scale. * Sufficient endurance, motor ability and balance to ambulate at least 10 meters continuously with moderate or less assistance. * Demonstrate gait impairment during ambulation such that gait instability or inefficient gait patterns \[gait pattern manifesting dragging or catching of the affected toes during swing phase of gait, or use of compensatory strategies such as circumducting the affected limb, vaulting with the unaffected limb or hiking the affected hip to clear the toes\] are exhibited. * Pass the Transcranial Magnetic Stimulation (TMS) Adult Safety Screen (TASS) except for items related specifically to stroke and the treatment for stroke.
Exclusion criteria
* Edema, skin breakdown, absent sensation of the affected lower limb which interferes with the peroneal nerve stimulator. * History of potentially fatal cardiac arrhythmias, such as ventricular tachycardia, supraventricular tachycardia, and rapid ventricular response atrial fibrillation with hemodynamic instability. * Demand pacemakers or any other implanted electronic systems. * Pregnant women, uncontrolled seizure disorder, Parkinson's Disease, Spinal cord injury, Traumatic brain injury with evidence of motor weakness, Multiple sclerosis. * Documented episode in the medical record of a seizure occurring 1 month or more post stroke for which the patient received consultation or treatment for said seizures. Seizures occurring within the first month following a stroke are not exclusionary unless followed by another seizure. * Fixed ankle plantar flexor contracture, peroneal nerve injury at the fibular head as the cause of foot-drop. * History of dementia, severely impaired cognition, communication or comprehension deficits. * Presence of severe or frequent headaches * History of Botulinum toxin (Botox) injection to either of the lower extremities within the 3 month period preceding study entry. * Have other medical conditions or are taking medications that compromise ambulation or balance. * Failure to meet established screening criteria for TMS or tDCS (i.e., TASS) * Principal Investigator's or Medical Monitor's discretion not to include a participant. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ankle Dorsiflexion Angle. Change From Baseline in Ankle Dorsiflexion Angle During the Swing Phase of Gait | Study week 1, and study weeks 5(± 5 days) and 8 (± 10 days). | Over ground laboratory assessments of gait: 1) Gait velocity and spatiotemporal gait parameters will be measured with the GAITRite system (CIR Systems, Inc., Havertown, PA) 28-35. 2) Hip, ankle, and knee angles during gait will be measured using the Simi Aktisys gait analysis system (Simi Reality Motion Systems; Postfach, Unterschleissheim Germany). LED markers are placed on the participant's lower extremity. Ankle, knee, and hip angle data is obtained simultaneously to evaluate motor strategies for overcoming gait impairments. Both types of data will be collected simultaneously as participants walk 10 meters across the GAITRite walkway at a self-selected speed for 5 repetitions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Slope of Recruitment Curve. Change From Baseline in the Slope of the Recruitment Curve Based on Motor Evoked Potentials (MEPs). | Study week 1, and study weeks 5(± 5 days) and 8 (± 10 days). | A Magstim 200 super rapid2 stimulator with a 110 mm double cone coil will deliver stimulation. First, the TMS motor threshold (MT) will be established and the best location for eliciting MEPs from the contralesional and ipsilesional TA muscle will be tracked on the subject's MRI scan in Brainsight. Recruitment curves will be obtained as follows: 1) delivering ten, single TMS pulses beginning at 70% of MT, 2) increasing TMS intensity by 10% and repeating the process up to 160% of the MT or until a plateau in the recruitment curve is reached, 3) offline data processing will be performed with the Matlab curve fitting toolbox and 4) the threshold, slope, and MEPmax, and the goodness of fit (R2) will be calculated. A change in the slope of the recruitment curve will indicate change in cortical excitability. |
| Change From Baseline in Stroke Impact Scale Scores | Study week 1, and study weeks 5(± 5 days) and 8 (± 10 days). | The Stroke Impact Scale-16 (SIS-16, completed by study team) is a standardized instrument 36-38 that assesses 3 functional domains in stroke patients including ADL / IADL, mobility, and social and occupational engagement. It consists of 64 - 5 point likert scale questions with a total score range of 64(lowest) to 320 (highest). |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited via study advertisements and referrals from physical therapy clinics
Participants by arm
| Arm | Count |
|---|---|
| Transcranial Direct Current Stim tDCS will be applied using a Soterix constant current stimulator with 5 x 5 cm (25cm2) carbon rubber electrodes (Covidien 664 REFX 2x2) applied to the scalp with 10-20 conductive paste. The anodal electrode will be placed over the lower extremity representation of primary motor cortex of the lesioned hemisphere \[established during TMS motor threshold testing (Baseline Testing) and the functional MRI assessment\]. The cathodal electrode will be placed over the contralateral motor cortex.
transcranial direct current stim (tDCS): During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down). During sham stimulation the stimulator is turned off. | 4 |
| Sham tDCS Sham stimulation will be performed by turning the stimulator off after the initial sensory experience (30 seconds).
transcranial direct current stim (tDCS): During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down). During sham stimulation the stimulator is turned off. | 2 |
| Total | 6 |
Baseline characteristics
| Characteristic | Transcranial Direct Current Stim | Sham tDCS | Total |
|---|---|---|---|
| Age, Continuous | 65.8 years STANDARD_DEVIATION 8.9 | 45 years STANDARD_DEVIATION 26.9 | 58.0 years STANDARD_DEVIATION 16.3 |
| Ankle dorsiflexion angle during the swing phase of gait | -9.28 degrees STANDARD_DEVIATION 3.1 | -0.19 degrees STANDARD_DEVIATION 4.39 | -6.25 degrees STANDARD_DEVIATION 10.21 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
| Slope of recruitment curve | 7.24 slope of regression line STANDARD_DEVIATION 0.71 | 5.19 slope of regression line STANDARD_DEVIATION 0.87 | 6.42 slope of regression line STANDARD_DEVIATION 2.09 |
| Stroke Impact Scale Score | 53.0 units on a scale STANDARD_DEVIATION 1.97 | 68.67 units on a scale STANDARD_DEVIATION 2.78 | 58.22 units on a scale STANDARD_DEVIATION 9.55 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 2 |
| other Total, other adverse events | 2 / 4 | 1 / 2 |
| serious Total, serious adverse events | 0 / 4 | 0 / 2 |
Outcome results
Primary
Ankle Dorsiflexion Angle. Change From Baseline in Ankle Dorsiflexion Angle During the Swing Phase of Gait
Over ground laboratory assessments of gait: 1) Gait velocity and spatiotemporal gait parameters will be measured with the GAITRite system (CIR Systems, Inc., Havertown, PA) 28-35. 2) Hip, ankle, and knee angles during gait will be measured using the Simi Aktisys gait analysis system (Simi Reality Motion Systems; Postfach, Unterschleissheim Germany). LED markers are placed on the participant's lower extremity. Ankle, knee, and hip angle data is obtained simultaneously to evaluate motor strategies for overcoming gait impairments. Both types of data will be collected simultaneously as participants walk 10 meters across the GAITRite walkway at a self-selected speed for 5 repetitions.
Time frame: Study week 1, and study weeks 5(± 5 days) and 8 (± 10 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active tDCS: Week 5 - Baseline. | Ankle Dorsiflexion Angle. Change From Baseline in Ankle Dorsiflexion Angle During the Swing Phase of Gait | 3.85 degrees | Standard Error 7.6 |
| Active tDCS: Week 8 - Baseline | Ankle Dorsiflexion Angle. Change From Baseline in Ankle Dorsiflexion Angle During the Swing Phase of Gait | .18 degrees | Standard Error 7.6 |
| Sham tDCS; Week 5 - Baseline. | Ankle Dorsiflexion Angle. Change From Baseline in Ankle Dorsiflexion Angle During the Swing Phase of Gait | -4.15 degrees | Standard Error 10.74 |
| Sham tDCS: Week 8 - Baseline. | Ankle Dorsiflexion Angle. Change From Baseline in Ankle Dorsiflexion Angle During the Swing Phase of Gait | -1.60 degrees | Standard Error 10.74 |
p-value: 0.05Mixed Models Analysis
Secondary
Change From Baseline in Stroke Impact Scale Scores
The Stroke Impact Scale-16 (SIS-16, completed by study team) is a standardized instrument 36-38 that assesses 3 functional domains in stroke patients including ADL / IADL, mobility, and social and occupational engagement. It consists of 64 - 5 point likert scale questions with a total score range of 64(lowest) to 320 (highest).
Time frame: Study week 1, and study weeks 5(± 5 days) and 8 (± 10 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active tDCS: Week 5 - Baseline. | Change From Baseline in Stroke Impact Scale Scores | 1.75 units on a scale | Standard Error 4.82 |
| Active tDCS: Week 8 - Baseline | Change From Baseline in Stroke Impact Scale Scores | 1.25 units on a scale | Standard Error 4.82 |
| Sham tDCS; Week 5 - Baseline. | Change From Baseline in Stroke Impact Scale Scores | 6.82 units on a scale | Standard Error 0.77 |
| Sham tDCS: Week 8 - Baseline. | Change From Baseline in Stroke Impact Scale Scores | 00. units on a scale | Standard Error 6.8 |
p-value: 0.05ANOVA
Secondary
Slope of Recruitment Curve. Change From Baseline in the Slope of the Recruitment Curve Based on Motor Evoked Potentials (MEPs).
A Magstim 200 super rapid2 stimulator with a 110 mm double cone coil will deliver stimulation. First, the TMS motor threshold (MT) will be established and the best location for eliciting MEPs from the contralesional and ipsilesional TA muscle will be tracked on the subject's MRI scan in Brainsight. Recruitment curves will be obtained as follows: 1) delivering ten, single TMS pulses beginning at 70% of MT, 2) increasing TMS intensity by 10% and repeating the process up to 160% of the MT or until a plateau in the recruitment curve is reached, 3) offline data processing will be performed with the Matlab curve fitting toolbox and 4) the threshold, slope, and MEPmax, and the goodness of fit (R2) will be calculated. A change in the slope of the recruitment curve will indicate change in cortical excitability.
Time frame: Study week 1, and study weeks 5(± 5 days) and 8 (± 10 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active tDCS: Week 5 - Baseline. | Slope of Recruitment Curve. Change From Baseline in the Slope of the Recruitment Curve Based on Motor Evoked Potentials (MEPs). | .98 Slope of a regression line | Standard Error 1.73 |
| Active tDCS: Week 8 - Baseline | Slope of Recruitment Curve. Change From Baseline in the Slope of the Recruitment Curve Based on Motor Evoked Potentials (MEPs). | .89 Slope of a regression line | Standard Error 1.73 |
| Sham tDCS; Week 5 - Baseline. | Slope of Recruitment Curve. Change From Baseline in the Slope of the Recruitment Curve Based on Motor Evoked Potentials (MEPs). | -1.32 Slope of a regression line | Standard Error 2.12 |
| Sham tDCS: Week 8 - Baseline. | Slope of Recruitment Curve. Change From Baseline in the Slope of the Recruitment Curve Based on Motor Evoked Potentials (MEPs). | -1.84 Slope of a regression line | Standard Error 2.12 |
p-value: 0.05ANOVA