Cerebrovascular Accident
Conditions
Keywords
Rehabilitation, Gait disorders, Chronic stroke
Brief summary
The study is a prospective interventional study to assess the changes in corticospinal excitability and spinal reflex excitability of in response to rehabilitative strategies and protocols that are commonly used during physical therapy treatment of gait disorders among post-stroke subjects. As part of this protocol, 55 individuals with chronic stroke will be assigned to either Cohort 1 or Cohort 2, and will participate in 1-18 gait training sessions. If interested, study participants can also complete both study cohorts sequentially (with at least 3-weeks duration between switching from one cohort to the second). The study examines the effects among two cohorts of post stroke patients. Cohort 1 will participate in 18 sessions of fast treadmill walking plus Functional Electrical Stimulation (FastFES) and Cohort 2 will participate in 1-3 sessions of FastFES and fast walking without FES.
Detailed description
Stroke is the number one cause of disability. Difficulty with walking affects most stroke survivors. Walking deficits (e.g. reduced ankle flexion during swing phase, decreased forward propulsion during terminal stance) can cause risks of falls, slow walking speed, increased effort of walking, and difficulties with activities of daily living. Restoration of walking ability can improve quality of life, and is perceived as a major goal of rehabilitation by stroke survivors. Examples of interventions that are used to rehabilitate walking post-stroke are functional electrical stimulation, fast treadmill walking, and bio- feedback. While recent research has focused on comparing the effectiveness of different gait rehabilitation interventions, the neural and biomechanical mechanisms underlying different gait rehabilitation strategies are unknown. FastFES is a novel gait training intervention that combines the beneficial effects of two independent interventions: Fast treadmill walking and FES. The FastFES intervention incorporates principles of physiology, biomechanics, motor control and learning, and predictions of forward-dynamic gait simulations to improve post-stroke gait. The overall purpose of this protocol is to assess the biomechanical and neurophysiologic effects of rehabilitative strategies and protocols that are commonly used during physical therapy treatment of gait disorders post-stroke among two cohorts of people. Aim 1 of the study will assess the changes in gait biomechanics, corticospinal excitability, and walking function during 18 sessions of gait retraining, with participants in Cohort 1. Aim 2 of the study assesses the effect of parameters such as walking speed (slow, fast, variable, split-belt walking), functional electrical stimulation parameters (short-term changes induced by fast versus FastFES, stimulation intensity, number of muscles stimulated), and bio-feedback on within-session changes in gait biomechanics, walking function, and corticospinal excitability, among participants in Cohort 2. Within Cohort 1, participants will receive identical treatment throughout the 18 training sessions (i.e. FastFES training). Within Cohort 2, participants will participate in 3 training sessions of both FastFES and fast walking training, with a 3-week break between the two types of training.
Interventions
DEVICEFast Walking with Fast Functional Electrical Stimulation (FES) Training
Functional electrical stimulation (FES) is a technique that causes a muscle to contract through the use of an electrical current. The therapist applies an electrical current to either the skin over the nerve, or over the bulk of the muscle, and this will cause a muscle contraction. The FES is delivered to 2 muscle groups (dorsiflexor and plantarflexor) timed appropriately with the gait cycle. FastFES gait training sessions may comprise up to six 6-minute bouts of walking with rest breaks between bouts (total 30-minutes of walking). The last training bout (bout 6) may comprise 6-minutes of over ground walking, during which subjects will be asked to walk as fast as they can. For safety, a physical therapist will walk with and guard the subject during over ground walking.
OTHERFast Walking
Fast walking training sessions will be similar to FastFES in duration, dosage, structure but no FES will be provided.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
American Heart Association
Emory University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Assignment to either Cohort 1 or Cohort 2 will occur simultaneously and will be based on the lab/personnel and subject schedules. Participants in Cohort 1 receive only FastFES. Participants in Cohort 2 will receive 3 sessions of FastFES and 3 sessions of fast walking without FES.
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Chronic stroke (\>6 months post stroke) * First (single) lesion * Able to walk with or without the use of a cane or walker * Sufficient cardiovascular health and ankle stability to walk for 6 minutes at a self-selected speed without an orthoses * Resting heart rate 40-100 beats per minute * Resting blood pressure between 90/60-70/90
Exclusion criteria
* Evidence of moderate/ severe chronic white matter disease or cerebellar stroke on MRI * Cerebellar signs (ataxic (drunken) gait or decreased coordination during rapid alternating hand or foot movements * Insulin dependent diabetes * History of lower extremity joint replacement * Score of \>1 on question 1b and \>0 on question 1c on NIH Stroke Scale * Inability to communicate with investigators * Neglect/hemianopia, or unexplained dizziness in last 6 months * Neurologic conditions other than stroke * Orthopedic problems in the lower limbs or spine (or other medical conditions) that limit walking * Contraindications to transcranial magnetic stimulation (TMS) are: history of seizures, metal implants in the head or face, history of recurring or severe headaches/migraine, headache within the past 24 hours, presence of skull abnormalities or fractures, hemorrhagic stroke, history of dizziness, syncope, nausea, or loss of consciousness in the past 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Motor Evoked Potentials (MEP) Amplitude Measure in milliVolt (mV) of FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2 | Baseline, week 3 (after 3 sessions of one intervention), week 6 (after 3 sessions of the other intervention) | Change from baseline in MEP amplitude (transverse abdominal (TA) muscle) is used as a measure of corticospinal excitability that is assessed using a non-invasive technique called transcranial magnetic stimulation (TMS). Electrical activity from muscles in response to the TMS will be collected using surface electromyography (EMG) sensors attached to muscles that play critical roles during FastFES versus Fast walking. TMS will be delivered using two Magstim 200 stimulators connected via a BiStim module. An average of 10 TMS-evoked MEP responses will be used to comparing mean peak-to-peak MEP amplitudes in response to suprathreshold TMS delivered to the hotspot. |
| Change in H-Reflex /M-Wave (Hmax/Mmax) Ratio Among FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2 | Baseline, week 3 (after 3 sessions of one intervention), week 6 (after 3 sessions of the other intervention) | Change from baseline in (Hmax/Mmax) ratio is used as a measure of spinal reflex excitability, that is assessed using peripheral electrical stimulation delivered to the nerves innervating the ankle muscles. An electrical stimulation electrode is placed just above the knee, and used as the anode for tibial nerve stimulation. Electrical stimulation is delivered via surface electrodes in a static position to the popliteal fossa. The subject's EMG activity will be recorded while the cathode is moved at the back of the knee to determine the location that provides the best EMG response (H-reflex). EMG activity will be recorded while 50-60 electrical stimuli (short 1 ms square pulses, ranging in intensity in milliAmpere(mA) 1-80), 7-10 seconds apart, are delivered to the muscle. Also 5-20 electrical stimulus pulses at intensities are delivered that elicit a percentage of the maximum reflex response. |
| Change in Motor Evoked Potentials (MEP) Amplitude Measure in milliVolt (mV) of FastFES After 18 Training Sessions in Cohort 1 | Baseline and up to 6 weeks | Change from baseline in MEP amplitude (TA muscle in a resting state) is used as a measure of corticospinal excitability that is assessed using a non-invasive technique called transcranial magnetic stimulation (TMS). Electrical activity from muscles in response to the TMS will be collected using surface electromyography (EMG) sensors attached to muscles that play critical roles during FastFES versus Fast walking. TMS will be delivered using two Magstim 200 stimulators connected via a BiStim module. An average of 10 TMS-evoked MEP responses will be used to comparing mean peak-to-peak MEP amplitudes in response to suprathreshold TMS delivered to the hotspot. |
| Change in H-Reflex /M-Wave (Hmax/Mmax) Ratio Among FastFES Versus Fast Walking After 18 Training Sessions in Cohort 1 | Baseline and up to 6 weeks | Change from baseline in (Hmax/Mmax) ratio is used as a measure of spinal reflex excitability, that is assessed using peripheral electrical stimulation delivered to the nerves innervating the ankle muscles. An electrical stimulation electrode is placed just above the knee, and used as the anode for tibial nerve stimulation. Electrical stimulation is delivered via surface electrodes in a static position to the popliteal fossa. The subject's EMG activity will be recorded while the cathode is moved at the back of the knee to determine the location that provides the best EMG response (H-reflex). EMG activity will be recorded while 50-60 electrical stimuli (short 1 ms square pulses, ranging in intensity in milliAmpere(mA) 1-80), 7-10 seconds apart, are delivered to the muscle. Also 5-20 electrical stimulus pulses at intensities are delivered that elicit a percentage of the maximum reflex response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Peak Anterior Ground Reaction Force (AGRF) of FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2 | Baseline, week 3 (after 3 sessions of one intervention), week 6 (after 3 sessions of the other intervention) | Change from baseline in peak AGRF during treadmill walking will be collected using a treadmill instrumented with two force platforms under each belt. Motion analysis data will be collected during 15- to 40-second long dynamic walking trials as subjects walk on a treadmill. |
| Change in Peak Anterior Ground Reaction Force (AGRF) of FastFES Versus Fast Walking After 18 Training Sessions in Cohort 1 | Baseline and up to 6 weeks | Change from baseline in peak AGRF during treadmill walking will be collected using a treadmill instrumented with two force platforms under each belt. Motion analysis data will be collected during 15- to 40-second long dynamic walking trials as subjects walk on a treadmill. |
Countries
United States
Participant flow
Recruitment details
Enrollment began in August 2013 and all study follow up was completed on May 1, 2019.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - FastFES Training Participants in Cohort 1 will receive 18 training sessions of FastFES (fast treadmill walking with electrical stimulation). | 2 |
| Cohort 2 - FastFES and Fast Walking Participants in Cohort 2 who complete 3 sessions of FastFES and 3 sessions of fast walking. | 22 |
| Total | 24 |
Baseline characteristics
| Characteristic | Cohort 2 - FastFES and Fast Walking | Total | Cohort 1 - FastFES Training |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 11 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 13 Participants | 1 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 22 Participants | 24 Participants | 2 Participants |
| Sex: Female, Male Female | 10 Participants | 12 Participants | 2 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 20 | 0 / 19 |
| other Total, other adverse events | 0 / 2 | 0 / 20 | 1 / 20 |
| serious Total, serious adverse events | 0 / 2 | 0 / 20 | 0 / 19 |
Outcome results
Primary
Change in H-Reflex /M-Wave (Hmax/Mmax) Ratio Among FastFES Versus Fast Walking After 18 Training Sessions in Cohort 1
Change from baseline in (Hmax/Mmax) ratio is used as a measure of spinal reflex excitability, that is assessed using peripheral electrical stimulation delivered to the nerves innervating the ankle muscles. An electrical stimulation electrode is placed just above the knee, and used as the anode for tibial nerve stimulation. Electrical stimulation is delivered via surface electrodes in a static position to the popliteal fossa. The subject's EMG activity will be recorded while the cathode is moved at the back of the knee to determine the location that provides the best EMG response (H-reflex). EMG activity will be recorded while 50-60 electrical stimuli (short 1 ms square pulses, ranging in intensity in milliAmpere(mA) 1-80), 7-10 seconds apart, are delivered to the muscle. Also 5-20 electrical stimulus pulses at intensities are delivered that elicit a percentage of the maximum reflex response.
Time frame: Baseline and up to 6 weeks
Population: This analysis includes participants from Cohort 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Three Sessions of FastFES | Change in H-Reflex /M-Wave (Hmax/Mmax) Ratio Among FastFES Versus Fast Walking After 18 Training Sessions in Cohort 1 | 24.49 percentage of Hmax/Mmax | Standard Deviation 45.88 |
Primary
Change in H-Reflex /M-Wave (Hmax/Mmax) Ratio Among FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2
Change from baseline in (Hmax/Mmax) ratio is used as a measure of spinal reflex excitability, that is assessed using peripheral electrical stimulation delivered to the nerves innervating the ankle muscles. An electrical stimulation electrode is placed just above the knee, and used as the anode for tibial nerve stimulation. Electrical stimulation is delivered via surface electrodes in a static position to the popliteal fossa. The subject's EMG activity will be recorded while the cathode is moved at the back of the knee to determine the location that provides the best EMG response (H-reflex). EMG activity will be recorded while 50-60 electrical stimuli (short 1 ms square pulses, ranging in intensity in milliAmpere(mA) 1-80), 7-10 seconds apart, are delivered to the muscle. Also 5-20 electrical stimulus pulses at intensities are delivered that elicit a percentage of the maximum reflex response.
Time frame: Baseline, week 3 (after 3 sessions of one intervention), week 6 (after 3 sessions of the other intervention)
Population: This analysis includes participants in Cohort 2 who have complete data for this assessment. There were issues with data collection during the training sessions and stimulus artifact causing noise in data, resulting in incomplete data for some participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Three Sessions of FastFES | Change in H-Reflex /M-Wave (Hmax/Mmax) Ratio Among FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2 | 4.14 percentage of Hmax/Mmax | Standard Deviation 0.05 |
| Three Sessions of Fast Walking | Change in H-Reflex /M-Wave (Hmax/Mmax) Ratio Among FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2 | 0.44 percentage of Hmax/Mmax | Standard Deviation 0.09 |
Primary
Change in Motor Evoked Potentials (MEP) Amplitude Measure in milliVolt (mV) of FastFES After 18 Training Sessions in Cohort 1
Change from baseline in MEP amplitude (TA muscle in a resting state) is used as a measure of corticospinal excitability that is assessed using a non-invasive technique called transcranial magnetic stimulation (TMS). Electrical activity from muscles in response to the TMS will be collected using surface electromyography (EMG) sensors attached to muscles that play critical roles during FastFES versus Fast walking. TMS will be delivered using two Magstim 200 stimulators connected via a BiStim module. An average of 10 TMS-evoked MEP responses will be used to comparing mean peak-to-peak MEP amplitudes in response to suprathreshold TMS delivered to the hotspot.
Time frame: Baseline and up to 6 weeks
Population: This analysis includes participants in Cohort 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Three Sessions of FastFES | Change in Motor Evoked Potentials (MEP) Amplitude Measure in milliVolt (mV) of FastFES After 18 Training Sessions in Cohort 1 | -0.02 mV | Standard Deviation 0.07 |
Primary
Change in Motor Evoked Potentials (MEP) Amplitude Measure in milliVolt (mV) of FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2
Change from baseline in MEP amplitude (transverse abdominal (TA) muscle) is used as a measure of corticospinal excitability that is assessed using a non-invasive technique called transcranial magnetic stimulation (TMS). Electrical activity from muscles in response to the TMS will be collected using surface electromyography (EMG) sensors attached to muscles that play critical roles during FastFES versus Fast walking. TMS will be delivered using two Magstim 200 stimulators connected via a BiStim module. An average of 10 TMS-evoked MEP responses will be used to comparing mean peak-to-peak MEP amplitudes in response to suprathreshold TMS delivered to the hotspot.
Time frame: Baseline, week 3 (after 3 sessions of one intervention), week 6 (after 3 sessions of the other intervention)
Population: This analysis includes participants in Cohort 2 who had complete data for this assessment. There were issues with data collection during the training sessions and stimulus artifact causing noise in data, resulting in incomplete data for some participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Three Sessions of FastFES | Change in Motor Evoked Potentials (MEP) Amplitude Measure in milliVolt (mV) of FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2 | 0.058 mV | Standard Deviation 0.11 |
| Three Sessions of Fast Walking | Change in Motor Evoked Potentials (MEP) Amplitude Measure in milliVolt (mV) of FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2 | 0.013 mV | Standard Deviation 0.2 |
Secondary
Change in Peak Anterior Ground Reaction Force (AGRF) of FastFES Versus Fast Walking After 18 Training Sessions in Cohort 1
Change from baseline in peak AGRF during treadmill walking will be collected using a treadmill instrumented with two force platforms under each belt. Motion analysis data will be collected during 15- to 40-second long dynamic walking trials as subjects walk on a treadmill.
Time frame: Baseline and up to 6 weeks
Population: This analysis includes participants in Cohort 1.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Three Sessions of FastFES | Change in Peak Anterior Ground Reaction Force (AGRF) of FastFES Versus Fast Walking After 18 Training Sessions in Cohort 1 | 15.40 Newtons.milliseconds (N.ms) | Standard Deviation 10.82 |
Secondary
Change in Peak Anterior Ground Reaction Force (AGRF) of FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2
Change from baseline in peak AGRF during treadmill walking will be collected using a treadmill instrumented with two force platforms under each belt. Motion analysis data will be collected during 15- to 40-second long dynamic walking trials as subjects walk on a treadmill.
Time frame: Baseline, week 3 (after 3 sessions of one intervention), week 6 (after 3 sessions of the other intervention)
Population: This analysis includes participants from Cohort 2 who had complete data for this assessment. There were issues with data collection during the training sessions and stimulus artifact causing noise in data, resulting in incomplete data for some participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Three Sessions of FastFES | Change in Peak Anterior Ground Reaction Force (AGRF) of FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2 | 8.68 Newtons.milliseconds (N.ms) | Standard Deviation 11.76 |
| Three Sessions of Fast Walking | Change in Peak Anterior Ground Reaction Force (AGRF) of FastFES Versus Fast Walking After 3 Training Sessions in Cohort 2 | -2.00 Newtons.milliseconds (N.ms) | Standard Deviation 12.76 |