Spastic Gait, Spastic
Conditions
Keywords
Spasticity, Stroke rehabilitation, Botulinum toxin type A injection, Robot, Knee
Brief summary
The purpose of this project is to examine and compare the immediate and long-term effects of combined Botulinum toxin type A(BoNT-A) injection with exoskeleton Robotic assisted gait training (RABT) in patients with post-stroke stiff-knee gait.
Detailed description
The aim of the study is to evaluate the effects of BoNT-A combining with overground exoskeleton robot for patients with post-stroke stiff-knee gait. Stiff-knee gait (SKG) is a common gait pattern in patients after stroke, characterized by limited knee flexion (KF) during the swing phase of walking. Botulinum toxin A (BoNT-A) injection in rectus femoris muscle is considered the gold standard procedure to treat SKG. Patients with this gait pattern would reduce walking speed, cause toe dragging, compromise the stability of walking, increase risk of falling, and interfere with daily activities. This randomized controlled trial will contribute to the accelerated refinement and development of efficient and effective treatment programs for patients with post-stroke spastic stiff knee gait. The Robot-assisted gait training (RAGT) has the potential to be an optimal adjunctive therapy following BoNT-A treatment. Combinations of BoNT-A and rehabilitation training are suggested to optimize the treatment effect for spasticity related disabilities.
Interventions
PROCEDUREBoNT-A injections
Botox brand BoNT-A Purified Neurotoxin Complex, (Allergan Pharmaceuticals, Irvine, CA) will be prepared by diluting lyophilized toxin with 0.9% saline to a concentration of 33-100 U/ml. depending on the size of the target muscle. Location of the targeted muscle will be confirmed by using echo guide. The total dose range is 100 units. The dose range of each target muscle is as below:100 units in rectus femoris.
OTHERRF BoNT-A injection in first period and robot therapy
Wearable overground exoskeleton lower extremity robot system will be used in this study. The robot lower extremity system consisted with bilateral motors for assisting left and right knees, a pelvis belt and chariot system for suspending the device, and thigh and shank cuffs for attaching the exoskeleton "links" to the user. Patients will wear receive exoskeleton lower extremity robot after BoNT-A injected in the affected rectus femoris, then start to do the functional ambulation training to do 1) walking over ground 2) walking with turning, 3) get in and out of chair, 4) crouching and rising, and 5) going up and down stairs. After a 3-month washout period crossover to none RF BoNT-A injection, and received second round of robot therapy.
OTHERRF BoNT-A injection in second period and robot therapy
Wearable overground exoskeleton lower extremity robot system will be used in this study. The robot lower extremity system consisted with bilateral motors for assisting left and right knees, a pelvis belt and chariot system for suspending the device, and thigh and shank cuffs for attaching the exoskeleton "links" to the user. Patients will wear receive exoskeleton lower extremity robot after BoNT-A injected (do not inject BoNT-A in the affected rectus femoris), then start to do the functional ambulation training to do 1) walking over ground 2) walking with turning, 3) get in and out of chair, 4) crouching and rising, and 5) going up and down stairs. After a 3-month washout period crossover to RF BoNT-A injection, and received second round of robot therapy.
Sponsors
Chang Gung Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
There will be a research code representing patients' identity, this code will not show patients' name, social security number, and home address. For the results of patients' visit and the diagnosis, the study moderator will maintain a confidential attitude and be careful to maintain patients' privacy.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ischemic or hemorrhagic stroke ≥ 3 months * Age ≥ 20 years * Functional Ambulation Category ≥4 * Affected rectus femoris spasticity (MAS between 1+ and 2) * BoNT-A treatment-naive or treated with BoNT-A ≥4 months in the affected leg before recruitment * Receiving oral muscle relaxants or other medication for spasticity were on a stable dose for≥2 months * Can obey simple order
Exclusion criteria
* Pregnant * Sensitivity to BoNT-A * Infection of the skin, soft tissue in the injection area * Participation in other trials * Fixed contractures or bony deformities in the affected leg * Previous treatment of the affected leg with neurolytic or surgical procedures (i.e., phenol block, tendon lengthening of transfer, tenotomy, muscle release, arthrodesis) * Severe cardiovascular comorbidity (i.e., recent myocardial infarction, heart failure, uncontrolled hypertension, orthostatic hypotension)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kinematic Analysis (Including ROM of Each L/E Joints、Change in Gait Speed in Gait Cycle、Change in Center of Mass、Stride Length) | Relative change from baseline at 5 months | Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. We calculate the relative change by subtracting the initial value from the final value and then dividing the answer by the absolute value of the initial number. (relative change = (post - baseline)/ baseline ×100%) Investigators will use a marker less motion capture system for kinematic analysis, use four high-definition cameras to record 30 fps at a resolution of 4 megapixels. The camera was placed uniformly 5 meters away from the center of the subject at the height of 1 meter, allowing for a maximum number of detections of the entire body. To analyze the kinematics of lower extremity, investigators use Open Pose, a real-time multi-person system, to detect human pose in 2D images Fromm the four high-definition cameras. Investigators will use this test to measure the angle of knee flexion and the step length (cm) of participants. |
| Data Analysis From the built-in Speed and Angle Sensors of the Exoskeleton Robot (Including ROM of the Joints, the Cyclogram Perimeter, the Cyclogram Area, Cyclogram Orientation, the Trend Symmetry, and the Square Root of the Sum of Squared Deviation | Relative change from baseline at 5 months | Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. A cyclogram is used to represent the functional relationship between joints during a full gait cycle, and is constructed by plotting two angles on the X-Y plane (the alteration of the hip and knee joint). It has several types of clinically relevant parameters, such as ROM of the joints, the cyclogram perimeter, the cyclogram area. And we can also compare the different between affected and unaffected side by looking at the cyclogram orientation, the trend symmetry, and the square root of the sum of squared deviation (A value of 0 indicates greater symmetry and coordination) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Emory Functional Ambulation Profile(mEFAP) | Relative change from baseline at 5 months | Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. The mEFAP is a clinical test that measures the time to ambulate through five common environmental terrains with or without an assistive device .It has been demonstrated to have a high inter-rater and test-retest reliability as a measure of gait capacity and functional ambulation in the post stroke patient population. The mEFAP comprises five timed tasks: (1) a 5-m walk on a hard floor; (2) a 5-m walk on a carpeted surface; (3) to rise from a chair, a 3-m walk, and return to a seated position (the timed "up-and-go" test); (4) a standardized obstacle course; and (5) to ascent and descent five stairs. The five timed sub scores will be adjusted by a multiplier for any necessary assistive device and then add together to derive a composite score. |
| Modified Ashworth Scale | Relative change from baseline at 5 months | Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. Spasticity of skeletal muscle in lower extremity was evaluated by using the MAS scale. It uses a 8-point scale (0, 1, 1+,2, 2+, 3, 3+, 4) to score the average resistance to passive movement for each join with higher score indicating higher spasticity. The MAS has shown good reliability and validity. Investigators assessed the MAS of knee flexor/ extensor, ankle dorsiflexor/planta flexor in sitting position. The maximum of MAS scale is 4, and the minimum is 0. The higher scores mean a worse outcome. |
| Medical Research Council Scale | Relative change from baseline at 5 months | Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. The MRC scale is a reliable measurement which ranges from 0 (no contraction) to 5 (normal power). Total scale combines all range and computes average scores, the higher scores mean a better outcome. The MRC scale will be used to examine the muscle strength of the affected hip flexion, knee flexion, knee extension, and ankle dorsiflexion. Select an appropriate testing posture based on the client's abilities.(If the client cannot be assessed in a standing position, use a sitting position instead, but it would result in a lower score.) |
| Pendulum Test | Relative change from baseline at 5 months | Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. The pendulum test was performed to assess spasticity of the knee extensors. During each trial, inertial measurement unit (IMU) data were recorded, including angular velocity from the gyroscope, linear acceleration from the accelerometer, and magnetic field from the magnetometer. Pendular parameters (first swing excursion and relaxation index) were derived from knee angle trajectories measured using an electrogoniometer. The proximal and distal sensor endblocks were secured 15 cm above and 15 cm below the lateral femoral epicondyle, respectively. The two sensor were used to obtain one integrated knee-joint angle signal based on the relative motion between segments, rather than two separate outputs. Previous study showed the pendular parameters can provide additional ambulatory information, as complementary to the MAS . |
| Berg Balance Scale | Relative change from baseline at 5 months | Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. The BBS is a 14-item scale, which is widely used to assess balance disorders in people with stroke, each item is scored from 0 to 4 points. The reliability and validity of the BBS are well established. Investigators used BBS for balance function assessment. The higher scores mean a better outcome. |
| Six-Minute Walking Test | Relative change from baseline at 5 months | Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. The 6MWT is commonly used to assess patients' cardiovascular or respiratory problems and is regarded as a submaximal test of aerobic capacity. Investigators will use 6MWT to assess walking endurance. It is now commonly used in stroke patients and is highly reliable in this group. The maximum distance covered on a 20-m walkway in 6 mins is recorded. |
| Isometric Strength | Relative change from baseline at 5 months | Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. Isometric strength was measured using the Biodex System 3a. Investigators use to test consisting of three knee flexion/extension isometric contractions at 30°, 45°, 90° knee flexion, and record data of isometric peak torque (Nm/kg).Five-second maximal voluntary isometric contraction (MVIC) trials were performed ten times. A rest of 15s was given between contractions for each trial, and the interval between two angles was approximately 2 min. Isometric peak torque (Nm/kg) was calculated as the highest value from the filtered torque data during each MVIC, which was normalized by the body mass. The isometric peak torque (Nm) was obtained from the Biodex System 3 software for both flexion and extension. |
Countries
Taiwan
Contacts
PRINCIPAL_INVESTIGATORHung Jen-Wen
Chang Gung Memorial Hospital-Kaohsiung Medical Center
Participant flow
Recruitment details
40 patients were screened for eligibility between August 1, 2023 and July 31, 2025 at Kaohsiung Chang Gung Memorial Hospital.
Pre-assignment details
30 of 40 participants were randomized. Of those not randomized, 4 declined to participate ,6 did not meeting inclusion criteria.
Baseline characteristics
| Characteristic | — |
|---|---|
| Affected Side left | 5 Participants |
| Affected Side right | 7 Participants |
| Age, Continuous | 50.9 years STANDARD_DEVIATION 10.29 |
| Botulinum toxin A dosage Lower extremity | 300.71 units STANDARD_DEVIATION 46.65 |
| Botulinum toxin A dosage Total | 516.67 units STANDARD_DEVIATION 151.05 |
| Education | 17.47 years STANDARD_DEVIATION 5.73 |
| Functional Ambulation Category | 4.64 scores on a scale STANDARD_DEVIATION 0.5 |
| Mini-Mental State Examination | 25.66 scores on a scale STANDARD_DEVIATION 4.56 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 30 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Taiwan | 15 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 13 Participants |
| stroke survival period | 40.26 months STANDARD_DEVIATION 32.54 |
| Use of Ankle-Foot Orthosis No | 17 Participants |
| Use of Ankle-Foot Orthosis Yes | 13 Participants |
| Use of Assisted devices none | 17 Participants |
| Use of Assisted devices One cane | 2 Participants |
| Use of Assisted devices Quadricane | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
None listed