Transcranial Direct Current Stimulation for Improving Gait Training in Stroke

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT01807637
• Collaborator: University of Central Arkansas (Other)
• Enrollment: 6
• Locations: 2
• Arms: 2
• Actual Duration (Months): 56.6
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke; Cerebral Vascular Accident	Device: transcranial direct current stim (tDCS)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Using Transcranial Direct Current Stimulation to Jump Start Gait Training in Chronic Stroke Patients
• Actual Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Nov 17, 2017
• Actual Study Completion Date: Nov 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Device: 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.
Placebo Comparator: sham tDCS Sham stimulation will be performed by turning the stimulator off after the initial sensory experience (30 seconds).	Device: 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 Exclusion Criteria for MRI Scan

• Claustrophobia, or the inability to lie still in a confined space

• Major medical disorders (e.g., HIV, cancer)

• Medications which may affect image quality (e.g., water pills)

• Magnetic metallic implants (such as screws, pins, shrapnel remnants, aneurysm clips, artificial heart valves, inner ear (cochlear) implants, artificial joints, and vascular stents), as these may heat, pull, or twist in the strong magnetic field of the MRI scanner

• Non-removable dental implants, such as braces or permanent retainers, as these will distort the MRI images we collect (note: filings, crowns, and silver or gold teeth are OK)

• Permanent makeup or tattoos with metallic dyes

• A positive pregnancy test (for females), since the effect of strong magnetic fields on the developing fetus remains unknown and inconclusive. (We will conduct a pregnancy test for all female participants on the day of the MRI scan.)

• Psychotic disorders (e.g., schizophrenia)

• Any other condition that the investigator believes might put the participant at risk

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Central Arkansas	Conway	Arkansas	United States	72035
2	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

• University of Arkansas
• University of Central Arkansas

Investigators

• Principal Investigator: Mark Mennemeier, PhD, University of Arkansas

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 21, 2014

More Information

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT01807637
• Other Study ID Numbers: 138159; 138159
• First Posted: Mar 8, 2013
• Last Update Posted: Dec 11, 2018
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Stroke

Study Results

Participant Flow

Recruitment Details	Subjects were recruited via study advertisements and referrals from physical therapy clinics

Arm/Group Title	Transcranial Direct Current Stim	Sham tDCS
Arm/Group Description	tDCS will be applied using a DeluxeSoterix 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. During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down).	Sham stimulation will be performed by turning the stimulator off after the initial sensory experience (30 seconds).
Period Title: Baseline
STARTED	4	2
COMPLETED	4	2
NOT COMPLETED	0	0
Period Title: Baseline
STARTED	4	2
COMPLETED	4	2
NOT COMPLETED	0	0
Period Title: Baseline
STARTED	4	2
COMPLETED	4	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Transcranial Direct Current Stim	Sham tDCS	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	4	2	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.8 (8.9)	45 (26.9)	58.0 (16.3)
Sex: Female, Male (Count of Participants)
Female	2 50%	0 0%	2 33.3%
Male	2 50%	2 100%	4 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	4 100%	2 100%	6 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	4 100%	2 100%	6 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Ankle dorsiflexion angle during the swing phase of gait (degrees) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [degrees]	-9.28 (3.10)	-0.19 (4.39)	-6.25 (10.21)
Slope of recruitment curve (slope of regression line) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [slope of regression line]	7.24 (0.71)	5.19 (.87)	6.42 (2.09)
Stroke Impact Scale Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	53.0 (1.97)	68.67 (2.78)	58.22 (9.55)

Outcome Measures

1. Primary Outcome

Title	Ankle Dorsiflexion Angle. Change From Baseline in Ankle Dorsiflexion Angle During the Swing Phase of Gait
Description	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).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active tDCS: Week 5 - Baseline.	Active tDCS: Week 8 - Baseline	Sham tDCS; Week 5 - Baseline.	Sham tDCS: Week 8 - Baseline.
Arm/Group Description	tDCS will be applied using a DeluxeSoterix 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. During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down).	tDCS will be applied using a DeluxeSoterix 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. During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down).	Sham stimulation will be performed by turning the stimulator off after the initial sensory experience (30 seconds).	Sham stimulation will be performed by turning the stimulator off after the initial sensory experience (30 seconds).
Measure Participants	4	4	2	2
Mean (Standard Error) [degrees]	3.85 (7.60)	.18 (7.60)	-4.15 (10.74)	-1.60 (10.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active tDCS: Week 5 - Baseline., Active tDCS: Week 8 - Baseline, Sham tDCS; Week 5 - Baseline., Sham tDCS: Week 8 - Baseline.
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.05
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	9.10
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.37
	Estimation Comments

2. Secondary Outcome

Title	Slope of Recruitment Curve. Change From Baseline in the Slope of the Recruitment Curve Based on Motor Evoked Potentials (MEPs).
Description	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).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active tDCS: Week 5 - Baseline.	Active tDCS: Week 8 - Baseline	Sham tDCS; Week 5 - Baseline.	Sham tDCS: Week 8 - Baseline.
Arm/Group Description	tDCS will be applied using a DeluxeSoterix 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. During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down).	tDCS will be applied using a DeluxeSoterix 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. During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down).	Sham stimulation will be performed by turning the stimulator off after the initial sensory experience (30 seconds).	Sham stimulation will be performed by turning the stimulator off after the initial sensory experience (30 seconds).
Measure Participants	4	4	2	2
Mean (Standard Error) [Slope of a regression line]	.98 (1.73)	.89 (1.73)	-1.32 (2.12)	-1.84 (2.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active tDCS: Week 5 - Baseline., Active tDCS: Week 8 - Baseline, Sham tDCS; Week 5 - Baseline., Sham tDCS: Week 8 - Baseline.
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.05
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.05
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 1.12
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Stroke Impact Scale Scores
Description	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).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active tDCS: Week 5 - Baseline.	Active tDCS: Week 8 - Baseline	Sham tDCS; Week 5 - Baseline.	Sham tDCS: Week 8 - Baseline.
Arm/Group Description	tDCS will be applied using a DeluxeSoterix 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. During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down).	tDCS will be applied using a DeluxeSoterix 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. During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down).	Sham stimulation will be performed by turning the stimulator off after the initial sensory experience (30 seconds).	Sham stimulation will be performed by turning the stimulator off after the initial sensory experience (30 seconds).
Measure Participants	4	4	2	2
Mean (Standard Error) [units on a scale]	1.75 (4.82)	1.25 (4.82)	6.82 (.77)	00. (6.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active tDCS: Week 5 - Baseline., Active tDCS: Week 8 - Baseline, Sham tDCS; Week 5 - Baseline., Sham tDCS: Week 8 - Baseline.
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.05
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.67
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 3.41
	Estimation Comments

Adverse Events

Time Frame	Adverse events data were collected over a 2 year period
Arm/Group Title	Transcranial Direct Current Stim		Sham tDCS
Arm/Group Description	tDCS will be applied using a DeluxeSoterix 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. During anodal tDCS, participants will receive 20 min at 2mA over motor cortex (with 30 seconds of ramp-up and ramp-down).		Sham stimulation will be performed by turning the stimulator off after the initial sensory experience (30 seconds).
All Cause Mortality
	Transcranial Direct Current Stim		Sham tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/2 (0%)
Serious Adverse Events
	Transcranial Direct Current Stim		Sham tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Transcranial Direct Current Stim		Sham tDCS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		1/2 (50%)
Cardiac disorders
CABG surgery	0/4 (0%)		1/2 (50%)
General disorders
headache	2/4 (50%)		0/2 (0%)
Musculoskeletal and connective tissue disorders
Rolled ankle	1/4 (25%)		0/2 (0%)
knee pain	0/4 (0%)		1/2 (50%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.