Clinical trial NCT07014098: Robot-Aided Off-Axis Neuromuscular Training for Knee OA
Official title: Effectiveness of Robot-Aided Off-Axis Neuromuscular Training for Knee Osteoarthritis: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Osteoarthritis of Knee
Keywords: knee osteoarthritis
robot-assisted
neuromuscular training
knee biomechanics
knee symptoms
evaluation-based training strategy
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
First posted: 2025-06-10
Enrollment: 120
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Although the primary knee motion occurs in flexion/extension, the frontal and transverse (off-axis) knee motions are smaller but crucial for maintaining joint stability and normal knee loading. Altered kinematics and neuromuscular control in off-axis knee motions have been reported in patients with knee osteoarthritis (OA), which are associated with excessive knee loading and the progression of knee OA. However, traditional rehabilitative treatments for people with knee OA and existing exercise equipment often focus on sagittal plane movement. Probably due to the technical limitations, there is a lack of convenient and effective equipment/method to train patients with knee OA in off-axis (frontal and transverse) planes.

The purpose of this study is to use a robot-aided elliptical training device to measure knee neuromechanical properties and to improve neuromuscular control in off-axis knee motions, aiming for joint de-loading and pain reduction for individuals with knee OA.

Detailed description: The device used in this study is provided by Rehabtek LLC, which has received U.S. federal grants to develop and commercialize this device.

Eligible knee osteoarthritis (OA) patients will be randomly assigned to three groups: (A) evaluation-based, progressive, neuromuscular training group; (B) traditional regular stepping group; and (C) usual care only group.

Participants in groups A \& B will undergo 3 assessment visits and 15 training sessions. Participants in group C will undergo 3 assessments and maintain usual care only.

Once the participants have consented, the first assessment visit will be scheduled before the training, which includes the neuromechanical and clinical assessments:

1. The neuromechanical assessments involve the off-axis knee moments and instability during the free-speed stepping and fast stepping tasks on the elliptical machine to see which off-axis directions (knee valgus, varus, internal rotation, and/or external rotation) or combination of directions show excessive moments. Off-axis instability, muscle strength, range of motion, stiffness, proprioception acuity, and knee moments during stepping will also be evaluated.

   A. Knee frontal-plane neuromechanical properties.
   * The participants sit with their knees in 0 degrees flexion. A fixture is used to hold the thigh near the femoral condyles steadily. The footplate is moved by a linear motor mediolaterally in the frontal plane, a 6-axis force sensor underneath the footplate, and a 6-DOF(degree of freedom) goniometer on the knee is used to measure knee motions. With the knee joint perturbed in varus-valgus motion, varus-valgus angle and torque can be determined.
   * With the participants in the seated position and relaxed, the participants' knee varus-valgus laxity and passive range of motion (ROM) will be determined when a specific passive resistance torque is reached at varus or valgus direction.
   * Knee varus-valgus proprioceptive acuity is measured by the threshold to detection of a passive movement in the respective varus and valgus directions. From the neutral position, the knee is randomly moved into either varus or valgus direction by the linear motor at a constant, slow speed. The blindfolded participant is instructed to push a trigger and report the direction of motion when he/she first sense which direction the knee is moving into. The motor stops the movement once the trigger is activated. Each participant completes 8 trials without complaints of pain or discomfort.
   * Tibial varus-valgus pain threshold is measured by the threshold to feel pain in the respective tibial varus-valgus directions. While the participant is seated relaxed, the footplate moves in varus-valgus direction. This movement occurs at a constant speed. The participant is asked to push a trigger and report the direction of pain when he/she first senses and the motor would stop and move back to the initial position.
   * For the active muscular contribution to varus-valgus stiffness, with the subject seated at 0 deg knee flexion, participants' ability to actively stabilize the lower leg against perturbations in varus-valgus direction is evaluated. First, the participants are relaxed and in a seated position while the footplate moves medially and laterally until a specific resistance torque limit is reached in each direction. Second, the participant is asked to resist medial-lateral movements imposed by the footplate. Active muscular contribution to varus-valgus stiffness is determined as the difference in stiffness between these two conditions.
   * Muscle strength measurement in varus-valgus direction With the subject seated at 0-degree knee flexion, the researchers examine the ability of the participants to actively generate torque in the frontal plane. The footplate is locked in the neutral position. Then the subject is asked to perform maximal voluntary isometric contraction in varus direction against the footplate. The participants are provided with real-time visual feedback of the amount of torque they generate. Then, the participants are asked to hold the maximum contraction for 4 seconds and then release it. The task is performed 3 times. Then, the participants are given 30 seconds of rest between each trial.

   The same procedure will be repeated for the evaluation of their valgus torque generation ability.

   B. Tibial internal-external rotation neuromechanical properties
   * Knee axial plane neuromechanical properties are quantified with the leg axially rotated by a pivoting motor underneath the footplate. Considering that femoral rotation is coupled with tibial rotation at extended knee positions, the test is conducted in the seated position, and the knee is flexed at 90 degrees to minimize the coupled rotations and allow for reliable testing of tibial rotation relative to the femur. The foot is strapped to the footplate with a 6-axis force sensor underneath. The tibial long axis is aligned with the Z-axis of the 6-axis force sensor and the pivoting motor underneath.
   * The zero tibial rotation angle is set with the second toe directed forward. To determine the torque-rotation relationship and joint ROM in tibial internal and external rotation, the foot and tibia are rotated slowly by the pivoting servomotor until a preset resistance torque (or position) limit is reached. The driving device then stops for 2 seconds before reversing the movement direction and rotating the knee until the preset torque (or position) limit in the opposite direction is reached. The position limits are determined manually by rotating the subject's tibia to the extreme internal and external rotation positions (within comfortable limits for the subject). Joint torque and force are measured continuously using the 6-axis torque sensor. Motor rotation is measured continuously using the motor encoder, and the 6-DOF goniometer is used to measure the knee motion directly.
   * Tibial internal-external rotation proprioceptive acuity is measured by the threshold to detection of a passive movement in the respective tibial internal or external rotation directions. From the neutral position, the knee is randomly moved into either tibial internal or external rotation direction by the pivoting motor at a constant, slow speed. The participant is instructed to push a trigger and report the direction of motion when he/she first sense which direction the knee is moving into. The motor stops the movement once the trigger is activated. Each participant completes 8 trials without complaints of pain or discomfort. Proprioceptive acuity is quantified by the tibial internal-external rotation angle, where the participant senses the motion, with a greater angle indicating worse acuity.
   * Tibial Internal-External Rotation Pain Threshold Tibial internal-external rotation pain threshold is measured by the threshold to feel pain in the respective tibial internal or external rotation directions. While the participant is seated relaxed, the footplate rotates in internal or external rotation direction, which induces tibial rotations. This movement occurs at a constant speed. The participant is asked to push a trigger and report the direction of pain when he/she first senses and the motor would stop and move back to the initial position.
   * Active muscular contribution to tibial internal-external rotation stiffness With the subject seated at 90 ° knee flexion, the researchers examine the ability of the subject to actively stabilize the lower leg against perturbations in directions of tibial internal/external rotations. First, the subject's seat relaxed while the footplate rotates internally and externally until a specific resistance torque limit is reached. Second, the participant is asked to resist the internal/external rotations imposed by the footplate. Active muscular contribution to tibial internal/external rotation stiffness is determined as the difference in stiffness between these two conditions.
   * Muscle strength measurement in producing internal/external rotation torque With the subject seated at 90-degree knee flexion, the ability of the subject to actively generate internal/external rotation torque is assessed. The footplate is locked in the neutral position. Then, the subject is asked to perform maximal voluntary isometric contraction of internal rotation against the footplate. The participants are provided with real-time visual feedback of the amount of torque they generate. Then, the participants are asked to hold the maximum contraction for 4 seconds and then release it. The participants perform the task 3 times. Then, the participants are given 30 seconds of rest between each trial.

   The same procedure will be repeated for the evaluation of participants' external rotation torque generation ability.

   C. Tests of walking

   - To evaluate participant gait biomechanics, a motion capture system is employed for recording overground walking behavior over a short distance with markers attached to the lower limbs, upper limbs, and trunk. This assessment is performed in the first evaluation session and during the following assessment sessions.

   D. Dynamic structural changes

   - The SWEU (Aixplorer Version 4.2; Supersonic Imagine, Aix-en-Provence, France) will be synchronized with the robot-controlled elliptical device. The ultrasound probe (4-15 MHz, Super Liner 15-4; Supersonic Imagine) will be stabilized by a 3-D printed holder at the medial knee to make sure the distal femur and proximal tibia can be visualized. The stiffness of distal femur and proximal tibia cartilage, and meniscus extrusion will be calculated at each time point that corresponds to the pain and stiffness test in the 4 off-axis knee motions.
2. The subject will be asked to complete self-reported outcome measure, including the knee injury and osteoarthritis outcome score (KOOS) or international knee documentation committee (IKDC), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, the Fremantle Knee Awareness Questionnaire (FreKAQ), Rated Perceived Exertion (RPE) Scale, Tegner activity scale, and visual analogue scale (VAS). The subjects also perform the Four Square Step Test, the 6-minute walk test, the 20-meter walk test, and time up and go (TUG), the 30-second sit-to-stand test. The passive and active range of motion of lower limb joints will be assessed. These evaluations are part of the clinical assessment. Knee girth and Q-angle will be measured as well. Single-leg squat and single-leg hop tests may be used as well.

The subjects will do off-axis training on the elliptical stepping system in our lab. The elliptical stepping system can detect the forces and torques in the lower limb during free-speed stepping and fast stepping and give real-time visual feedback if forces in one direction are excessive.

Training in group A will be based on the specific biomechanical needs of each subject. We will put the footplates of the elliptical in specific outward/inward positions or make some modifications to the foot position in the sagittal and frontal planes. Then the researchers ask subjects to perform stepping on the elliptical at their self-selected speed. Training in group B will be traditional elliptical regular stepping. Training in the control group will be usual care.

For both group A \& B, the training protocol will be conducted 3 times a week for 5 weeks. Each training session will last about 40 minutes. The amount of usual care in all three groups will be documented and considered as a potential cofounder in the statistical analysis.

In group A, functional electrical stimulation (FES) may be utilized to activate target muscles around the knee joint selectively. The purpose will be to increase muscle strength in weak muscles to improve function.

For groups A \& B, after the 5-week training ends, the same outcome measures will be reassessed immediately after the training, and 8 weeks post-training. as the initial visit. For group C, the same measurements will be performed 3 times with the same time intervals as groups A \& B.

Healthy age-sex matched subjects undergo one assessment session. All the assessment procedures mentioned above will be conducted for healthy subjects as well, except the pain threshold detection section and self-reported outcome measures (KOOS, IKDC, WOMAC, and VAS).

As part of the assessment and training sessions, the researchers will measure participants' blood pressure, heart rate, and oxygen saturation level at the beginning and the end of each session. The researchers will also monitor participants' heart rate and oxygen saturation during the elliptical test.

Eligibility criteria: Inclusion Criteria:

* Age 45 - 75 years.
* Meets the ACR classification criteria for knee OA (clinical + radiographic criteria); Kellgren-Lawrence grade II-III.
* Persistent knee pain ≥ 3 months.
* Able to independently complete elliptical training (6 minutes without interruption).

Exclusion Criteria:

* Other inflammatory joint diseases (e.g., rheumatoid arthritis).
* Knee trauma, surgery, or intra-articular injections within the past year.
* History of knee or hip replacement.
* Cardiovascular disease or uncontrolled hypertension contradict to exercises.
* Neurological impairment (e.g., stroke, Parkinson's disease, radicular pain).
* Cognitive impairment (Montreal cognitive assessment \< 22).
* Currently participating in another rehabilitation intervention study for the lower limb.

Primary outcomes:
measure: Peak knee adduction moment
timeFrame: Baseline, immediately after the 5-week training, and follow-up evaluation 8-week post-training
measure: Knee pain
timeFrame: Baseline, immediately after the 5-week training, and follow-up evaluation 8-week post-training
Secondary outcomes:
measure: Knee proprioception acuity in off-axis directions
timeFrame: Baseline, immediately after the 5-week training, and follow-up evaluation 8-week post-training
measure: Knee range of motions in off-axis directions
timeFrame: Baseline, immediately after the 5-week training, and follow-up evaluation 8-week post-training
measure: Functional ability
timeFrame: Baseline, immediately after the 5-week training, and follow-up evaluation 8-week post-training
measure: Heath-related quality of life
timeFrame: Baseline, immediately after the 5-week training, and follow-up evaluation 8-week post-training
Other outcomes:
Locations:
Study officials:
affiliation: University of Maryland, Baltimore
name: Li-Qun Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
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