Exoskeleton Robotic Assisted Gait Training in Spastic Stroke Post Botulinum Toxin A Injection

To Estimate the Efficacy of Botulinum Toxin A Injection Combing With Exoskeleton Robotic Assisted Gait Training in Stroke Patients With Spastic Stiff Knee Gait: Motor Function Performance and Neurophysiological Evaluation

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.

Study Overview

• Status: Completed
• Conditions: Spastic; Spastic Gait
• Intervention / Treatment: Procedure: BoNT-A injections; Other: RF BoNT-A injection in first period and robot therapy; Other: RF BoNT-A injection in second period and robot therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung
    • Kaohsiung City, Kaohsiung, Taiwan, 833
      • Department of Rehabilitation, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RF BoNT-A injection in first period and robot therapy; Training session included 40 minutes Robotic Therapy, the group will receive 2 sessions per week, for 12 weeks.	Procedure: BoNT-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.; Other: RF 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.
Experimental: RF BoNT-A injection in second period and robot therapy; Training session included 40 minutes Robotic Therapy, the group will receive 2 sessions per week, for 12 weeks.	Procedure: BoNT-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.; Other: RF 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kinematic Analysis (Including ROM of Each L/E Joints、Change in Gait Speed in Gait Cycle、Change in Center of Mass、Stride Length)	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.	Relative change from baseline at 5 months
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	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)	Relative change from baseline at 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Emory Functional Ambulation Profile(mEFAP)	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.	Relative change from baseline at 5 months
Modified Ashworth Scale	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.	Relative change from baseline at 5 months
Medical Research Council Scale	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.)	Relative change from baseline at 5 months
Pendulum Test	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 .	Relative change from baseline at 5 months
Berg Balance Scale	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.	Relative change from baseline at 5 months
Six-Minute Walking Test	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.	Relative change from baseline at 5 months
Isometric Strength	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.	Relative change from baseline at 5 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nottingham Extended Activities of Daily Living Index	Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. The Nottingham Extended Activities of Daily Living Index (Eadl) is made up of 22 items divided into 4 sections, each item is scored from 0 to 3 points. Investigators only use Eadl index mobility subdomain to assess the community participation level of participants, which includes 6 items and ranges from 0 to 12, with higher scores indicating better performance.	Relative change from baseline at 5 months
Activities-specific Balance Confidence	Results are expressed as relative change from baseline, which is a unitless number or expressed as a percentage. The Activities-specific Balance confidence (ABS) scale is a questionnaire developed to assess older individual's balance confidence in performing daily activities. ABC scale consists of a wide continuum of less and more challenging daily activities. The ABS scale has 16 items, representing daily activities. Participants are asked to answer, with a score from 0% (not confident at all) to 100% (completely confident) in increments of 10%, how confident they are in performing each activity. The average score obtained is an indication on balance confidence.	Relative change from baseline at 5 months

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Hung Jen-Wen, Chang Gung Memorial Hospital-Kaohsiung Medical Center

Publications and helpful links

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Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Actual): July 31, 2025
• Study Completion (Actual): July 31, 2025

Study Registration Dates

• First Submitted: September 13, 2023
• First Submitted That Met QC Criteria: October 2, 2023
• First Posted (Actual): October 6, 2023

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: December 30, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Knee; Robot; Spasticity; Stroke rehabilitation; Botulinum toxin type A injection
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Muscle Spasticity; Gait Disorders, Neurologic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Neurotransmitter Agents; Membrane Transport Modulators; Cholinergic Agents; Neuromuscular Agents; Acetylcholine Release Inhibitors; Botulinum Toxins, Type A; incobotulinumtoxinA
• Other Study ID Numbers: NMRPG8N0051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No