Electrical Stimulation for Recovery of Ankle Dorsiflexion in Chronic Stroke Survivors

• Sponsor: MetroHealth Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01029912
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), Case Western Reserve University (Other)
• Enrollment: 26
• Location: 1
• Arms: 2
• Duration (Months): 21
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Ankle dorsiflexor weakness (paresis) is one of the most frequently persisting consequences of stroke. The purpose of this exploratory study is to compare two different treatments -- Contralaterally Controlled Neuromuscular Electrical Stimulation (CCNMES) and Cyclic Neuromuscular Electrical Stimulation (cNMES) -- for improved recovery of ankle movement and better walking after stroke.

Condition or Disease	Intervention/Treatment	Phase
Stroke; Hemiparesis; Lower Extremity Paresis	Device: Electrical stimulator	N/A

Detailed Description

Ankle dorsiflexor weakness results in inefficient and unstable gait. While routine physical therapy is beneficial, for many individuals it remains limited in its effectiveness, and consequently many stroke survivors have difficulty walking safely or remain non-ambulatory. Ankle-foot-orthoses (AFOs) are often prescribed to provide ankle stability, but because they limit ankle mobility they may actually inhibit recovery of dorsiflexion. Advanced rehabilitation techniques that emphasize active, repetitive, goal-oriented movement of the impaired limb have produced measurable functional improvements, yet a significant degree of lower extremity disability often remains. In addition, some of these emerging therapies are difficult to administer and are applicable only to patients who retain at least some degree of ambulation. Thus, there is a need for alternative treatments.

This is an exploratory study of an innovative neuromuscular electrical stimulation (NMES) treatment for restoring lower extremity motor control following stroke. We will investigate whether stroke survivors with chronic footdrop recover voluntary ankle dorsiflexion after a novel treatment of NMES. Surface electrodes will deliver stimulation to dorsiflex the ankle with an intensity that is proportional to the amount of dorsiflexion of the other unimpaired ankle. Thus, voluntary dorsiflexion of the unaffected ankle produces stimulated dorsiflexion of the affected ankle. We refer to this stimulation paradigm as Contralaterally Controlled Neuromuscular Electrical Stimulation (CCNMES). In contrast to existing peroneal nerve stimulators, CCNMES is not intended to be used to assist ambulation; rather it is intended as solely a motor retraining paradigm that may reduce lower extremity impairment and improve ambulation. The primary objective of the proposed study is to obtain pilot data so that an estimate can be made of the efficacy of CCNMES in reducing lower extremity impairment and improving ambulation.

Twenty-six chronic stroke survivors (>6 months post-stroke) will be randomized to either CCNMES or cyclic NMES, an intervention that provides electrical stimulation of the ankle dorsiflexors, but with preprogrammed timing and intensity. For both groups, the treatment will last 6 weeks. Assessments of ankle impairment and ambulation will be made at baseline and at end of treatment.

This study is the first randomized controlled trial of CCNMES for restoring ankle dorsiflexion in patients with chronic hemiplegia.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Contralaterally Controlled NMES in Chronic Ankle Dorsiflexor Paresis After Stroke
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CCNMES Contralaterally Controlled Neuromuscular Electrical Stimulation (CCNMES) Electrical Stimulator	Device: Electrical stimulator; 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.
Active Comparator: Cyclic NMES Cyclic Neuromuscular Electrical Stimulation (NMES) Electrical Stimulator	Device: Electrical stimulator; 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.

Outcome Measures

Primary Outcome Measures

1. Change in Lower Extremity Fugl-Meyer Score at End of Treatment [2 timepoints: Prior to treatment, and End of treatment at 6 weeks.]

   The Lower Extremity Fugl-Meyer (LEFM) Assessment is a measure of lower limb motor impairment. Participants are asked to attempt to perform a list of isolated and simultaneous movements of the hip, knee, and ankle that take into account synergy patterns, isolated strength, coordination, and hypertonia. Each movement attempt is graded on a 3-point ordinal scale (0, cannot perform; 1, perform partially; and 2, perform fully) and these subscores are summed to provide a maximum score of 34, minimum score of 0. Higher scores are considered to be a better outcome. For each individual, the score prior to treatment was subtracted from the score at end of the 6-week treatment. Then for each treatment group, these change scores were averaged.

2. Change in Gait Velocity (cm/Sec) at End of Treatment [2 timepoints: Prior to treatment, and End of treatment at 6 weeks.]

   Gait velocity was assessed using a motion capture and analysis system which collected spatio-temporal data as the participant walked 5-meters 10 times at a self-selected comfortable speed within the field of view of the motion capture system. A higher gait velocity is considered to be a better outcome. For each individual, the gait velocity prior to treatment was subtracted from the gait velocity at end of the 6-week treatment. Then for each treatment group, these change values were averaged.

3. Change in Time (Sec) to Complete the Modified Emory Functional Ambulation Profile (MEFAP). [2 timepoints: Prior to treatment, and End of treatment at 6 weeks.]

   The MEFAP is a measure of functional ambulation, measuring the time to ambulate through 5 common environmental terrains: 1) 5-meter walk on a hard floor, 2) 5-meter walk on a carpeted floor, 3) rise from a chair, 3-meter walk, return to seated position, 4) standardized obstacle course (bricks to step over), 5) stair ascent and descent. The five times subscores were added to derive a total time. Lower times are considered to be a better outcome. For each individual, the MEFAP completion time prior to treatment was subtracted from the MEFAP completion time at end of the 6-week treatment. Then for each treatment group, these change values were averaged.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 21 to 80 years

• 6 months from a first clinical non-hemorrhagic or hemorrhagic stroke

• Medically stable

• Unilateral lower extremity hemiparesis

• Ankle dorsiflexor strength of ≤4/5 on the Medical Research Council (MRC) scale, while seated

• Able to ambulate 16 feet (5 meters) continuously with minimal assistance or less, without the use of an ankle-foot orthosis (AFO).

• AFO is clinically indicated (footdrop during ambulation or inefficient gait patterns)

• Neuromuscular electrical stimulation (NMES) of the paretic ankle dorsiflexors produces ankle dorsiflexion to neutral without pain.

• Full voluntary dorsiflexion of the contralateral ankle

• Skin intact on hemiparetic lower extremity

• Able to don the NMES system or caregiver available to assist with device if needed.

• Able to hear and respond to stimulator auditory cues

• Able to follow 3-stage commands

• Able to recall 2 of 3 items after 30 minutes

Exclusion Criteria:

• Brainstem stroke

• Severely impaired cognition and communication

• History of peroneal nerve injury

• History of Parkinson's, spinal cord injury, traumatic brain injury, or multiple sclerosis

• Uncontrolled seizure disorder

• Uncompensated hemi-neglect (extinguishing to double simultaneous stimulation)

• Edema of the affected lower extremity

• Absent sensation of lower leg and foot

• Evidence of deep venous thrombosis or thromboembolism

• History of cardiac arrhythmias with hemodynamic instability

• Cardiac pacemaker or other implanted electronic system

• Botulinum toxin injections to any lower extremity muscle in the last 3 months

• Pregnancy

• Currently receiving Physical Therapy for the lower extremity

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MetroHealth Medical Center	Cleveland	Ohio	United States	44109

Sponsors and Collaborators

• MetroHealth Medical Center
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Case Western Reserve University

Investigators

• Principal Investigator: Jayme S. Knutson, PhD, Case Western Reserve University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Cleveland Functional Electrical Stimulation Center

Publications

• Khaslavskaia S, Sinkjaer T. Motor cortex excitability following repetitive electrical stimulation of the common peroneal nerve depends on the voluntary drive. Exp Brain Res. 2005 May;162(4):497-502. Epub 2005 Feb 9.
• Knutson JS, Harley MY, Hisel TZ, Chae J. Improving hand function in stroke survivors: a pilot study of contralaterally controlled functional electric stimulation in chronic hemiplegia. Arch Phys Med Rehabil. 2007 Apr;88(4):513-20.
• Knutson JS, Hisel TZ, Harley MY, Chae J. A novel functional electrical stimulation treatment for recovery of hand function in hemiplegia: 12-week pilot study. Neurorehabil Neural Repair. 2009 Jan;23(1):17-25. doi: 10.1177/1545968308317577. Epub 2008 Sep 23.
• Luft AR, McCombe-Waller S, Whitall J, Forrester LW, Macko R, Sorkin JD, Schulz JB, Goldberg AP, Hanley DF. Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial. JAMA. 2004 Oct 20;292(15):1853-61. Erratum in: JAMA. 2004 Nov 24;292(20):2470.
• Nudo RJ, Wise BM, SiFuentes F, Milliken GW. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science. 1996 Jun 21;272(5269):1791-4.
• Robbins SM, Houghton PE, Woodbury MG, Brown JL. The therapeutic effect of functional and transcutaneous electric stimulation on improving gait speed in stroke patients: a meta-analysis. Arch Phys Med Rehabil. 2006 Jun;87(6):853-9.
• Rushton DN. Functional electrical stimulation and rehabilitation--an hypothesis. Med Eng Phys. 2003 Jan;25(1):75-8.
• Sheffler LR, Hennessey MT, Naples GG, Chae J. Peroneal nerve stimulation versus an ankle foot orthosis for correction of footdrop in stroke: impact on functional ambulation. Neurorehabil Neural Repair. 2006 Sep;20(3):355-60.

• Responsible Party: Jayme Knutson, Assistant Professor, Physical Medicine and Rehabilitation, MetroHealth Medical Center
• ClinicalTrials.gov Identifier: NCT01029912
• Other Study ID Numbers: R21HD061593; R21HD061593
• First Posted: Dec 10, 2009
• Last Update Posted: Dec 7, 2017
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Keywords provided by Jayme Knutson, Assistant Professor, Physical Medicine and Rehabilitation, MetroHealth Medical Center: Stroke; Hemiplegia; Footdrop; Electrical Stimulation; Motor Relearning; Neuroplasticity
• Additional relevant MeSH terms: Muscle Weakness; Stroke; Paresis

Study Results

Participant Flow

Arm/Group Title	CCNMES	Cyclic NMES
Arm/Group Description	Contralaterally Controlled Neuromuscular Electrical Stimulation (Electrical Stimulator) CCFES Electrical Stimulator: 6-week intervention Home: Self-administered active repetitive CCNMES-mediated ankle dorsiflexion exercise performed ten 51-minute sessions (three 15-min sets separated by 3-min rest) per week at home. Lab: 15 minutes of therapist-guided CCFES-mediated ankle exercise + 30 minutes of gait training in the laboratory twice a week.	Cyclic Neuromuscular Electrical Stimulation (Electrical Stimulator) Cyclic NMES Electrical Stimulator: 6-week intervention Home: Self-administered active repetitive Cyclic NMES-mediated ankle dorsiflexion exercise performed ten 51-minute sessions (three 15-min sets separated by 3-min rest) per week at home. Lab: 15 minutes of therapist-guided Cyclic NMES-mediated ankle exercise + 30 minutes of gait training in the laboratory twice a week.
Period Title: Overall Study
STARTED	14	12
COMPLETED	12	12
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	CCNMES	Cyclic NMES	Total
Arm/Group Description	Contralaterally Controlled Neuromuscular Electrical Stimulation (Electrical Stimulator) Electrical stimulator: 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.	Cyclic Neuromuscular Electrical Stimulation (Electrical Stimulator) Electrical stimulator: 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.	Total of all reporting groups
Overall Participants	12	12	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.7 (13.7)	59.3 (9.1)	58.0 (11.4)
Sex: Female, Male (Count of Participants)
Female	4 33.3%	6 50%	10 41.7%
Male	8 66.7%	6 50%	14 58.3%
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	6 50%	5 41.7%	11 45.8%
White	6 50%	7 58.3%	13 54.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Years Since Stroke (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	2.7 (1.8)	3.6 (3.9)	3.1 (3.0)
Lower Extremity Fugl-Meyer Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	19.1 (6.8)	18.9 (7.0)	19.0 (6.8)
Time to complete Modified Emory Functional Ambulation Profile (MEFAP) in seconds (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	120.7 (86.3)	118.6 (86.5)	119.7 (84.5)
Gait velocity (cm/sec) (cm/sec) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm/sec]	39.9 (22.3)	38.3 (19.1)	39.1 (20.4)

Outcome Measures

1. Primary Outcome

Title	Change in Lower Extremity Fugl-Meyer Score at End of Treatment
Description	The Lower Extremity Fugl-Meyer (LEFM) Assessment is a measure of lower limb motor impairment. Participants are asked to attempt to perform a list of isolated and simultaneous movements of the hip, knee, and ankle that take into account synergy patterns, isolated strength, coordination, and hypertonia. Each movement attempt is graded on a 3-point ordinal scale (0, cannot perform; 1, perform partially; and 2, perform fully) and these subscores are summed to provide a maximum score of 34, minimum score of 0. Higher scores are considered to be a better outcome. For each individual, the score prior to treatment was subtracted from the score at end of the 6-week treatment. Then for each treatment group, these change scores were averaged.
Time Frame	2 timepoints: Prior to treatment, and End of treatment at 6 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CCNMES	Cyclic NMES
Arm/Group Description	Contralaterally Controlled Neuromuscular Electrical Stimulation (Electrical Stimulator) Electrical stimulator: 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.	Cyclic Neuromuscular Electrical Stimulation (Electrical Stimulator) Electrical stimulator: 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.
Measure Participants	12	12
Mean (Standard Error) [units on a scale]	0.93 (0.65)	1.8 (0.77)

2. Primary Outcome

Title	Change in Gait Velocity (cm/Sec) at End of Treatment
Description	Gait velocity was assessed using a motion capture and analysis system which collected spatio-temporal data as the participant walked 5-meters 10 times at a self-selected comfortable speed within the field of view of the motion capture system. A higher gait velocity is considered to be a better outcome. For each individual, the gait velocity prior to treatment was subtracted from the gait velocity at end of the 6-week treatment. Then for each treatment group, these change values were averaged.
Time Frame	2 timepoints: Prior to treatment, and End of treatment at 6 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CCNMES	Cyclic NMES
Arm/Group Description	Contralaterally Controlled Neuromuscular Electrical Stimulation (Electrical Stimulator) Electrical stimulator: 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.	Cyclic Neuromuscular Electrical Stimulation (Electrical Stimulator) Electrical stimulator: 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.
Measure Participants	12	12
Mean (Standard Error) [cm/sec]	3.0 (2.1)	1.2 (2.6)

3. Primary Outcome

Title	Change in Time (Sec) to Complete the Modified Emory Functional Ambulation Profile (MEFAP).
Description	The MEFAP is a measure of functional ambulation, measuring the time to ambulate through 5 common environmental terrains: 1) 5-meter walk on a hard floor, 2) 5-meter walk on a carpeted floor, 3) rise from a chair, 3-meter walk, return to seated position, 4) standardized obstacle course (bricks to step over), 5) stair ascent and descent. The five times subscores were added to derive a total time. Lower times are considered to be a better outcome. For each individual, the MEFAP completion time prior to treatment was subtracted from the MEFAP completion time at end of the 6-week treatment. Then for each treatment group, these change values were averaged.
Time Frame	2 timepoints: Prior to treatment, and End of treatment at 6 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CCNMES	Cyclic NMES
Arm/Group Description	Contralaterally Controlled Neuromuscular Electrical Stimulation (Electrical Stimulator) Electrical stimulator: 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.	Cyclic Neuromuscular Electrical Stimulation (Electrical Stimulator) Electrical stimulator: 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.
Measure Participants	12	12
Mean (Standard Error) [seconds]	-9.6 (2.6)	-3.2 (4.1)

Adverse Events

Arm/Group Title	CCNMES		Cyclic NMES
Arm/Group Description	Contralaterally Controlled Neuromuscular Electrical Stimulation (Electrical Stimulator) Electrical stimulator: 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.		Cyclic Neuromuscular Electrical Stimulation (Electrical Stimulator) Electrical stimulator: 6-week intervention 15 minutes of therapist-guided stimulated ankle exercise + 30 minutes of physical therapy in the laboratory twice a week. Self-administered active repetitive ankle dorsiflexion exercise performed twice a day, 6 days a week at home using the device.
All Cause Mortality
	CCNMES		Cyclic NMES
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CCNMES		Cyclic NMES
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	CCNMES		Cyclic NMES
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Discomfort from stimulation	1/12 (8.3%)	1	1/12 (8.3%)	1

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.