Hemorrhagic Stroke, Ischemic Stroke
Conditions
Keywords
stroke
Brief summary
There are over 7 million stroke survivors in the US alone, with approximately 795,000 new cases annually. Despite the best available physiotherapy, 30-60% of stroke survivors remain affected by difficulty walking, with foot weakness often being the main cause. Given that post-stroke gait impairments remain poorly addressed, new methods that can provide lasting improvements are necessary. Brain-computer interface (BCI) technology may be one such novel approach. BCI technology enables "direct brain control" of external devices such as assistive devices and prostheses by translating brain waves into control signals. When BCI systems are integrated with functional electrical stimulation (FES) systems, they can be used to deliver a novel physical therapy to improve movement after stroke. BCI-FES systems are hypothesized to stimulate recovery after stroke beyond that of conventional physical therapy.
Detailed description
Preliminary research indicates that applying this technique to foot weakness after stroke is safe and may improve walking function. Hence, this warrants further investigation to: 1. determine if BCI-FES therapy can provide lasting gains in walking in chronic stroke patients; 2. determine what factors influence BCI-FES therapy; and 3. explicitly elucidate the underlying neural repair mechanisms. First, a Phase II clinical trial in patients with foot drop due to chronic stroke will compare the effect of BCIFES dorsiflexion therapy to that of dose- and intensity-matched standard physical therapy (Aim 1). Comparing the improvement in walking speed and other secondary outcome measures between the two groups will test if BCI-FES therapy provides functional and neurological gains beyond those of standard physical therapy. The relationship between the patient baseline characteristics (walking speed, ankle function, stimulated muscle responses, brain wave features, sensation) and the outcomes will determine what features influence responsiveness to BCI-FES dorsiflexion therapy (Aim 2). Finally, the underlying mechanism driving the improvements of BCI-FES will be studied (Aim 3). Determining that BCI-FES therapy can provide improvements beyond that of standard therapy may lead to a new treatment for stroke patients. The underlying mechanism can inform the design of future physical therapy techniques or improve current ones. Finally, BCI-FES therapy may ultimately become a novel form of physical therapy to reduce post-stroke disability, and in turn reduce the public health burden of stroke.
Interventions
BEHAVIORALPhysiotherapy two hours
This will consist of a standardized regimen of activities typical of conventional post-stroke gait therapy, including passive/active range of motion exercises (to reduce/prevent excessive plantarflexor contractures), lower-extremity muscle strengthening, and a progression from treadmill to overground walking exercises. A total of 12 sessions will be performed at 3x/week.
DEVICEBCI-FES dorsiflexion therapy
BCI technology enables "direct brain control" of external devices such as assistive devices and prostheses by translating brain waves into control signals. When BCI systems are integrated with functional electrical stimulation (FES) systems, they can be used to deliver a novel physical therapy to improve movement after stroke. The automated software will analyze the data to generate and calibrate a BCI decoder. In the online phase, the subjects will perform 20-25 BCI-FES runs. In each run, subjects will follow 10 alternating epochs of 10-s long idling/dorsiflexion textual cues, and respond by either idling or attempting dorsiflexion to elicit BCI-FES mediated contractions of the TA muscle.
BEHAVIORALPhysiotherapy one hour
This will consist of a standardized regimen of activities typical of conventional post-stroke gait therapy, including passive/active range of motion exercises (to reduce/prevent excessive plantarflexor contractures), lower-extremity muscle strengthening, and a progression from treadmill to overground walking exercises. A total of 12 sessions will be performed at 3x/week.
Sponsors
University of California, Irvine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The outcomes assessors will be blinded to the whether participants are in Group 1 or 2.
Intervention model description
The study is design as an early Phase II two-arm randomized trial. The experimental group will receive BCI-FES dorsiflexion therapy paired with conventional physiotherapy (Group 1), while the control arm will receive dose- and intensity-matched conventional physiotherapy (Group 2). A total of 80 chronic stroke survivors with gait impairment due to foot-drop will be recruited and randomized evenly into the 2 groups (33/group).
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age18-80 years inclusively at time of consent; 2. Radiologically confirmed stroke, ischemic or intracerebral hemorrhage (ICH) in etiology, with day of onset at least 26 weeks prior to day of randomization 3. Gait velocity\<0.8 m/s at screening and baseline visits. 4. Foot-drop in affected limb as defined by dorsiflexion active range of motion (AROM) via goniometry in seated position foot dangling is less than passive range of motion and less than 15 degrees. 5. Plantarflexors spasticity\<3 on modified Ashworth Scale; 6. Can walk \>10 m (with or without ankle foot orthosis (AFO), and cane or walker permitted) at a supervised level; 7. Can tolerate FES with pain no more than 4 on pain analog scale and has adequate muscle response of dorsiflexion ≥10 degrees; 8. Passive Range of Motion at least 0 degrees ankle dorsiflexion in subtalar neutral or with FES
Exclusion criteria
1. A major, active, coexistent medical, neurological (apart from stroke) or psychiatric disease (apart from stroke), including alcoholism or dementia, orthopedic injuries, that substantially affects gait. \*\*Because old orthopedic injuries may or may not affect gait, at the discretion of the site's study PI, exclusion criterion #2 related to orthopedic injuries can be waived if the injury was not on the stroke affected side and the joint/muscles are back to normal motor and range of motion function. 2. A major medical disorder that substantially reduces the likelihood that a subject will be able to comply with all study procedures or safely complete study procedures. This includes, but not limited to documented serious cardiac conditions, serious pulmonary conditions, legal blindness, end stage renal or liver disease, pulmonary embolism or deep venous thrombosis. 3. Resting systolic blood pressure above 170, diastolic blood pressure above 100 at screening and baseline evaluations 4. Implanted electronic device (e.g. pacemaker) or skull metallic implants (e.g. cranioplasty plate covering the leg motor area); 5. Deficits in communication that interfere with reasonable study participation: language or attention impairment (score\>1 on NIH Stroke Scale items 9 and 11, respectively) 6. Significant cognitive impairment, defined as Montreal Cognitive Assessment score \< 22 (For those with aphasia: \*\*Because Montreal Cognitive Assessment scores may be difficult to interpret for patients with aphasia, at the discretion of the site's study PI, exclusion criterion #5 ("MoCA score cannot be \<22") can be waived) 7. A new symptomatic stroke occurs apart from the index stroke during the screening process and prior to randomization 8. Life expectancy \< 6 months 9. Skin breakdown over electrical stimulation sites; 10. Received chemical denervation (eg Botox) to legs in the preceding 6 months, or expectation that chemical denervation will be administered to the leg prior to expected completion of the study 11. Unable or unwilling to perform study procedures/therapy, or expectation of non-compliance with study procedures/therapy 12. Pregnancy; 13. Significant pain (visual analog scale \>4), chest pain, or shortness of breath with walking. 14. Receiving any outside concurrent physical therapy involving the lower extremities after enrollment in the study up to 1 month post treatment 15. Any general medical condition and psychosocial situation that substantially interferes with reasonable participate in study appointments 16. Non-English speaking, such that subject does not speak sufficient English to comply with study procedures 17. Concurrent enrollment in another investigational interventional study 18. Severe depression, defined as Geriatric Depression Scale Score \>11: \*\*Because Geriatric Depression scale scores may be difficult to interpret for some patients, at the discretion of the site's study PI, exclusion criterion #17 ("Geriatric Depression score cannot be \>11") can be waived) 19. Concurrent use of FES orthosis for gait. 20. A new symptomatic stroke occurs apart from the index stroke during the screening process and prior to randomization If TMS Eligible (note that potential subjects who do not qualify for TMS will not be excluded from the main study, they will only be excluded from undergoing TMS procedures): 21. TMS: Metallic hardware on the scalp (e.g. vascular clips or cranioplasty mesh) 22. TMS: Implanted medication pumps, intracardiac line, or central venous catheter 23. TMS: History of cortical stroke or other cortical lesion such as brain tumor 24. TMS: Prior diagnosis of seizure or epilepsy 25. TMS: Any electrical, mechanical, or magnetic implants 26. TMS: History of neurosurgery 27. TMS: uncontrolled Migraine headaches 28. TMS: Any current medications that affect seizure threshold such as tricyclic antidepressants and neuroleptics 29. TMS: Unstable medical conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gait Velocity | Baseline to End of Therapy (4 weeks after initiation of therapy) | Gait velocity will be assessed by measuring the time to traverse the middle 6 m of a 10-m walkway (5 repetitions/assessment). Scores are reported in meters/second with higher scores indicating better function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dorsiflexion Range of Motion | Baseline and end of therapy (4 weeks after initiation of therapy) | The paretic foot will be placed in a dangling, subtalar neutral position idling, while the tibia is perpendicular to the ground and the femur horizontal to the ground. A goniometer will be used to measure the maximum dorsiflexion angle, in degrees. 0 degrees indicates a neutral ankle position (foot horizontal to the ground, while tibia is perpendicular to the ground). Positive degrees indicate a maximum dorsiflexion angle above the neutral position, while negative degrees indicates a maximum angle below the neutral position (a larger, more positive measure indicates higher function). |
| Gait Endurance (Six Minute Walk Test: 6MWT) | Baseline to End of Therapy (4 weeks after initiation of therapy) | The distance walked over 6 minutes. Score is reported in meters and higher score indicates better function. |
| Fall Frequency | Baseline to End of Therapy (4 weeks after initiation of therapy) | Rate of falls experienced by subjects |
| EEG Map (Electroencephalogram) | Baseline to End of Therapy (4 weeks after initiation of therapy) | Subjects will undergo 64-channel EEG recording as they engage in 100 alternating 10-s long epochs of idling and attempted dorsiflexion. The EEG modulation, defined as the change in alpha (8-12 Hz) and beta (13-30 Hz) band power during attempted dorsiflexion (compared to idling) will be calculated and averaged over all epochs and across all channels. Change in EEG alpha and beta band power will be express as percentage with respect to the idle state. Specifically, the change in the Channel Cz will be reported given its primary salience to attempted dorsiflexion. |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.30 years STANDARD_DEVIATION 12.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Gait Velocity | 0.38 m/s STANDARD_DEVIATION 0.23 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 30 |
| other Total, other adverse events | 3 / 32 | 2 / 30 |
| serious Total, serious adverse events | 7 / 32 | 3 / 30 |
Outcome results
None listed