Biomechanical and Neural Mechanisms of Post-stroke Gait Training

Sponsor

Emory University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04380454

Collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Enrollment

Location

Arms

53.6

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study seeks to develop an understanding of how, why, and for whom fast treadmill walking (Fast) and Fast with functional electrical stimulation (FastFES) induce clinical benefits, allowing future development of cutting-edge, individually-tailored gait treatments that enhance both gait quality and gait function.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Device: Grass S8800 stimulator with SIU8TB stimulus isolation unit; UDel stimulator Other: Fast treadmill walking	N/A

Detailed Description

Stroke gait deficits are complex and multi-factorial, posing a problem well-matched to the NIH precision medicine initiative. Stroke gait impairments adversely affect kinematics and kinetics in all paretic lower limb joints, disrupt stance and swing phases, and are marked by inter-limb asymmetry. One intervention cannot target all post-stroke gait deficits. Multiple factors, including biomechanics, energy cost, and functioning and integrity of corticomotor neural pathways can influence stroke gait function and training-induced gait improvements.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

65 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Biomechanical and Neural Mechanisms of Post-stroke Gait Training

Actual Study Start Date :

Mar 16, 2021

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fast treadmill walking with functional electrical stimulation Fast treadmill walking with functional electrical stimulation (FastFES) is a targeted intervention that provides motor level stimulation-induced cues to improve ankle propulsion. FES is delivered only to the paretic ankle muscles, enhancing afferent ascending as well as descending corticomotor drive. Increased corticomotor drive in lesioned corticomotor circuits in turn promotes improved timing and intensity of muscle activation in the paretic plantar- and dorsi-flexor muscles, increasing plantarflexor moment and propulsion from the paretic ankle.	Device: Grass S8800 stimulator with SIU8TB stimulus isolation unit; UDel stimulator Functional electrical stimulation (FES) is a targeted intervention that provides motor level stimulation-induced cues to improve ankle propulsion. An electrical stimulator will be used to deliver stimulation during walking (Grass S8800 stimulator with SIU8TB stimulus isolation unit; UDel stimulator). A customized, real-time system will be used to control the stimulator and deliver stimulation during appropriate phases of the gait cycle. Stimulation will be delivered to the ankle dorsiflexors when the subject's foot is in the air (swing phase). Stimulation will be delivered to the ankle plantarflexors during the terminal stance phase of gait. 30-Hz variable frequency stimulation trains 170 will be delivered during gait. It comprises 18 training sessions (3/week). FES intensity is determined at the start of every training session as motor-level stimulation that elicits appropriate functional movements. Other: Fast treadmill walking Fast treadmill walking (Fast) is a non-targeted intervention where no specific instructions are provided to target practice to the paretic leg or specific ankle deficits.It comprises 18 training sessions (3/week). Each training session includes six 6-minute walking bouts with 5-minute breaks between bouts
Active Comparator: Fast treadmill walking Fast treadmill walking (Fast) is a non-targeted intervention that provides similar structure, dose, and intensity of stepping practice as FastFES, but does not include FES, and no specific instructions are provided to target practice to the paretic leg or specific ankle deficits	Other: Fast treadmill walking Fast treadmill walking (Fast) is a non-targeted intervention where no specific instructions are provided to target practice to the paretic leg or specific ankle deficits.It comprises 18 training sessions (3/week). Each training session includes six 6-minute walking bouts with 5-minute breaks between bouts

Arm

Intervention/Treatment

Experimental: Fast treadmill walking with functional electrical stimulation

Fast treadmill walking with functional electrical stimulation (FastFES) is a targeted intervention that provides motor level stimulation-induced cues to improve ankle propulsion. FES is delivered only to the paretic ankle muscles, enhancing afferent ascending as well as descending corticomotor drive. Increased corticomotor drive in lesioned corticomotor circuits in turn promotes improved timing and intensity of muscle activation in the paretic plantar- and dorsi-flexor muscles, increasing plantarflexor moment and propulsion from the paretic ankle.

Device: Grass S8800 stimulator with SIU8TB stimulus isolation unit; UDel stimulator

Functional electrical stimulation (FES) is a targeted intervention that provides motor level stimulation-induced cues to improve ankle propulsion. An electrical stimulator will be used to deliver stimulation during walking (Grass S8800 stimulator with SIU8TB stimulus isolation unit; UDel stimulator). A customized, real-time system will be used to control the stimulator and deliver stimulation during appropriate phases of the gait cycle. Stimulation will be delivered to the ankle dorsiflexors when the subject's foot is in the air (swing phase). Stimulation will be delivered to the ankle plantarflexors during the terminal stance phase of gait. 30-Hz variable frequency stimulation trains 170 will be delivered during gait. It comprises 18 training sessions (3/week). FES intensity is determined at the start of every training session as motor-level stimulation that elicits appropriate functional movements.

Other: Fast treadmill walking

Fast treadmill walking (Fast) is a non-targeted intervention where no specific instructions are provided to target practice to the paretic leg or specific ankle deficits.It comprises 18 training sessions (3/week). Each training session includes six 6-minute walking bouts with 5-minute breaks between bouts

Active Comparator: Fast treadmill walking

Fast treadmill walking (Fast) is a non-targeted intervention that provides similar structure, dose, and intensity of stepping practice as FastFES, but does not include FES, and no specific instructions are provided to target practice to the paretic leg or specific ankle deficits

Other: Fast treadmill walking

Outcome Measures

Primary Outcome Measures

Change in gait propulsion [Baseline (pre-training), Post 6 week (after 18 training sessions), 6-week follow-up (6-weeks after completion of training)]
Gait biomechanics testing will be conducted in the motion analysis assessing gait asymmetry. A 7-camera system will be used to collect motion analysis data. Ground reaction forces during treadmill walking will be collected using force platforms.
Change in TMS motor evoked potential (MEP) amplitude [Baseline (pre-training), Post 6 week (after 18 training sessions), 6-week follow-up (6-weeks after completion of training)]
Change in MEP amplitude 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.

Secondary Outcome Measures

Change in intracortical facilitation (ICF) [Baseline (pre-training), Post 6 week (after 18 training sessions), 6-week follow-up (6-weeks after completion of training)]
Intracortical facilitation (ICF) can be elicited by transcranial magnetic stimulation (TMS) of the motor cortex. Change in Intracortical facilitation (ICF) will be recorded.
Change in H-max/M-max ratio for the soleus [Baseline (pre-training), Post 6 week (after 18 training sessions), 6-week follow-up (6-weeks after completion of training)]
H-max/M-max ratio for the soleus will be calculated. Change 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 muscles.
Change in energy cost (EC) of walking [Baseline (pre-training), Post 6 week (after 18 training sessions), 6-week follow-up (6-weeks after completion of training)]
Energy cost (EC) of walking is measured as the rate of energy use, computed from rates of oxygen consumption and carbon dioxide production. Elevated EC related to activity intolerance, sedentary lifestyle, and physical deconditioning.
Change in ankle peak plantarflexor moment during gait [Baseline (pre-training), Post 6 week (after 18 training sessions), 6-week follow-up (6-weeks after completion of training)]
Gait biomechanics testing will be conducted in the motion analysis assessing gait asymmetry. A 7-camera system will be used to collect motion analysis data. Ground reaction forces (GRF) during treadmill walking will be collected using force platforms. Marker and GRF data will be used to calculate peak plantarflexor moment during gait.
Change in ankle power during gait [Baseline (pre-training), Post 6 week (after 18 training sessions), 6-week follow-up (6-weeks after completion of training)]
Gait biomechanics testing will be conducted in the motion analysis assessing gait asymmetry. A 7-camera system will be used to collect motion analysis data. Ground reaction forces (GRF) during treadmill walking will be collected using force platforms. Marker and GRF data will be used to calculate peak ankle power during gait.
Change in over ground walking endurance [Baseline (pre-training), Post 6 week (after 18 training sessions), 6-week follow-up (6-weeks after completion of training)]
Over ground walking endurance will be measured by the distance ambulated during the 6-minute walk test.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

6 months since stroke
age 40-90 years
single cortical or subcortical ischemic stroke
able to walk 10-meters with or without assistive device
sufficient cardiovascular health and ankle stability to walk on treadmill for 2-minutes at self-selected speed without orthosis
resting heart rate 40-100 bpm.

Exclusion Criteria:

hemorrhagic stroke,
cerebellar signs (ataxic ("drunken") gait or decreased coordination during rapid alternating hand or foot movements,
score of >1 on question 1b and >0 on question 1c on NIH Stroke Scale,
inability to communicate with investigators,
musculoskeletal conditions or pain that limit walking,
neglect/hemianopia, or unexplained dizziness in last 6 months,
neurologic conditions or diagnoses other than stroke,
lack of sensation in lower limb affected by stroke,

Additional exclusion criteria due to contra-indications to TMS (measurement of corticospinal excitability) 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 6 months.